Lupus recent issues

Ammonium sulphate precipitation to measure antibodies to double-stranded DNA: a simple clinical test for diagnosis and management of patients with systemic lupus erythematosus

Pincus, T. — Tue, 24 Nov 2009 08:56:19 PST

Polymorphisms in the DNA repair gene XRCC1 and associations with systemic lupus erythematosus risk in the Taiwanese Han Chinese population

Tue, 24 Nov 2009 08:56:19 PST

XRCC1 plays a central role in mammalian DNA repair processes. Two polymorphisms of XRCC1, rs1799782 (Arg > Trp at codon 194) and rs25487 (Arg > Gln at codon 399), are common in the Han Chinese population. Our objective was to analyze the relationship between these two functional single-nucleotide polymorphisms (SNPs) and systemic lupus erythematosus (SLE) in the Taiwanese Han Chinese population. Genotyping was performed by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) on 172 SLE patients and 160 normal controls. Our data indicate that the frequency of A/G at codon 399 differed between patients and controls (p = 0.01; odds ratio: 1.80; 95% confidence interval: 1.17—2.75), but the allelic frequency analysis did not reveal significant differences. For the SNP at codon 194, there were no differences in either allelic or genotype frequencies between SLE patients and normal subjects. Clinical association studies of SLE symptoms revealed the involvement of the A/G polymorphism at codon 399 in SLE pathogenesis. Our results indicate that a functional SNP at codon 399 of XRCC1 is associated with the development of SLE. Lupus (2009) 18, 1246—1251.

Prognostic factors in patients with systemic lupus erythematosus admitted to the intensive care unit

Tue, 24 Nov 2009 08:56:19 PST

The objectives of this study were to identify risk factors associated with mortality in patients with systemic lupus erythematosus (SLE) admitted to the intensive care unit (ICU) and to evaluate the usefulness of Acute Physiologic and Chronic Health Evaluation (APACHE) II score to predict outcomes in these patients, through the use of a retrospective patient record review from a multidisciplinary intensive care unit in a teaching hospital. One hundred and four patients with SLE admitted to the ICU were included in the study. The mean age of patients was 32.44 years, 96.2% were female and 61.5% were admitted with infection. The mean APACHE II score was 19.7, 46.2% had acute renal dysfunction, 67.3% received inotropics/ vasopressors, 27.9% pulmonary artery catheter and 74% invasive mechanical ventilation. The mean length of stay in ICU was 18.5 days and mortality rate was 32.7%. In the univariate logistic regression analysis, factors associated with mortality were high APACHE II score, use of inotropics/vasopressors, pulmonary artery catheter and invasive mechanical ventilation. High APACHE II score and use of inotropics/vasopressors remained significant in the multi-variate analysis. The area under the receiver operating characteristic curve of the APACHE II score to predict mortality was 0.689 (95% CI 0.586—0.791 p = 0.002) and the Hosmer— Lemeshow ² was 5.094 (p = 0.747). We conclude that the mortality rate in patients with SLE admitted to the ICU is high. The most common cause of admission was infection. The factors associated with mortality were high APACHE II score and the use of inotropics/vasopressors. APACHE II score was unable to accurately predict mortality. Lupus (2009) 18, 1252—1258.

Lack of association between HLA-G 14-bp polymorphism and systemic lupus erythematosus in a Han Chinese population

Tue, 24 Nov 2009 08:56:19 PST

HLA-G is a non-classical HLA-class Ib molecule with multiple immunoregulatory properties. A 14-bp insertion/deletion polymorphism in the HLA-G gene has been suggested to influence the expression of HLA-G and to associate with certain pathological conditions, including autoimmune diseases. We investigated the influence of the 14-bp insertion/deletion polymorphism in the HLA-G gene on disease susceptibility in systemic lupus erythematosus by genotyping this polymorphism in 231 patients with systemic lupus erythematosus and 367 healthy controls and analyzing the levels of soluble HLA-G in a subset of patients with systemic lupus erythematosus and healthy subjects from a Han Chinese population. No statistically significant differences were observed in the frequencies of the 14-bp insertion/deletion HLA-G alleles or genotypes between controls and patients with systemic lupus erythematosus. However, a significant increased expression of soluble HLA-G was noted in patients with systemic lupus erythematosus (mean value = 230.2 U/ml vs 118.3 U/ml in controls, p = 0.0001). Moreover, patients with high levels of soluble HLA-G presented with higher disease activity and had more neurological involvement. Our results do not support the HLA-G 14-bp insertion/deletion polymorphism as a genetic factor influencing systemic lupus erythematosus susceptibility. It is possible that the expression of soluble HLA-G in systemic lupus erythematosus is enhanced as part of a mechanism to try to restore the tolerance process towards auto-antigens and to counteract inflammation. However, the participation of this molecule in the pathological process of the disease also could not be excluded. Lupus (2009) 18, 1259—1266.

Prognostically distinct clinical patterns of systemic lupus erythematosus identified by cluster analysis

To, C., Mok, C., Tang, S., Ying, S., Wong, R., Lau, C. — Tue, 24 Nov 2009 08:56:19 PST

The objective of this study was to evaluate the patterns of clinical manifestations and their mortality in a large cohort of Chinese patients with systemic lupus erythematosus. The cumulative clinical manifestations of a large group of Chinese systemic lupus erythematosus patients who fulfilled at least four American College of Rheumatology criteria for systemic lupus erythematosus were studied. Patients were divided into distinct groups by using the K-mean cluster analysis. Clinical features, prevalence of proliferative lupus nephritis (World Health Organization class III, IV), autoantibody profile, and treatment data were compared and the standardized mortality ratios were calculated for each cluster of patients. There were 1082 patients included in the study (mean age at systemic lupus erythematosus diagnosis 30.5 years; mean systemic lupus erythematosus duration 10.3 years). Three distinct groups of patients were identified. Cluster 1 (n = 347) was characterized predominantly by mucocutaneous manifestations (malar rash, discoid rash, photosensitivity, oral ulcer) and arthritis but having the lowest prevalence of serositis, hematologic manifestations (hemolytic anemia, leukopenia, and thrombocytopenia), and proliferative lupus nephritis. Patients in cluster 2 (n = 409) had mainly renal and hematological manifestations but having the lowest prevalence of mucocutaneous manifestations. Pulmonary and gastrointestinal manifestations were significantly more frequent in cluster 2 than the other clusters. Cluster 3 patients (n = 326) had the most heterogeneous features. Besides having a high prevalence of mucocutaneous manifestations, serositis and hematologic manifestations, renal involvement, and proliferative lupus nephritis was also most prevalent among the three clusters. Patients in cluster 2 had a much higher standardized mortality ratio [standardized mortality ratio 7.23 (6.7—7.7), p < 0.001] than those in cluster 3 [standardized mortality ratio 1.27 (1.1—1.5), p = 0.005] and cluster 1 [standardized mortality ratio 0.95 (0.5—1.7), p = 0.86]. In conclusion, patients with systemic lupus erythematosus could be clustered into prognostically distinct patterns of clinical manifestations. Lupus (2009) 18, 1267—1275.

Sensitivity and specificity of autoantibody tests in the differential diagnosis of lupus nephritis

Tue, 24 Nov 2009 08:56:19 PST

Several studies have investigated the potential of various autoantibody tests in the diagnosis of systemic lupus erythematosus (SLE). Many lupus patients initially present with glomerulonephritis. In that clinical situation the main differential diagnosis are other forms of glomerulonephritis. In this study the diagnostic value of nine test kits for autoantibody against ANA, dsDNA, circulating immune complexes, C1q, nucleosomes, histones and Sm as well as C3 and C4 levels was evaluated in 39 patients with biopsy-proven lupus nephritis in comparison to 43 patients suffering from other forms of glomerulonephritis. The most useful test was an anti-nucleosome antibody enzyme-linked immunosorbent assay (ELISA) with a sensitivity of 90% and a specificity of 88%. All tests for anti-dsDNA antibodies (Crithidia luciliae Anti-dsDNA, BINDAZYME Anti-dsDNA, FARRZYME high avidity Anti-dsDNA) were of moderate sensitivity and very good specificity. Decreasing the cut-off for the conventional anti-dsDNA ELISA (BINDAZYME) considerably increased its sensitivity (87%) without loss of specificity (90%). Tests for anti-C1q and immune complexes performed worse than the antidsDNA tests. As anti-histone and Sm antibodies are present only in a minority of lupus nephritis patients they are of limited value in diagnosing the disease. In conclusion, testing for anti-nucleosome antibodies and the conventional anti-dsDNA ELISA with lower cut-off provide the best diagnostic aids for differentiation of lupus nephritis from other forms of glomerulonephritis. Lupus (2009) 18, 1276—1280.

Work disability in systemic lupus erythematosus is prevalent and associated with socio-demographic and disease related factors

Tue, 24 Nov 2009 08:56:19 PST

Our objectives were to examine the prevalence of work disability (WD) and factors associated with job loss in systemic lupus erythematosus (SLE) in a large, multi-centered Canadian sample to determine the current prevalence of WD and identify the contribution of disease activity, damage, and co-morbidities with respect to WD in this cohort. Cross-sectional data on WD status from the 1000 Canadian Faces of Lupus database (a multi-center multi-ethnic cohort of SLE patients) along with clinical measures (number of ACR criteria ever, SLICC Damage Index, SLAM, SLEDAI, SF-36 and Charlson Co-morbidity Index scores), demographic features (age, sex, high school education, household income, marital status, disease duration, employment status) and co-morbidities (including self-reported fibromyalgia, arthralgias, depression and fatigue) were used in bivariate and logistic regression analyses. The 1137 SLE patients had a mean age of 50 years (SE 0.75) and mean disease duration was 18 years (SE 0.70); 19.09% were work disabled and 49.78% were employed. Those with WD were more likely than non-WD SLE patients to have: a higher number of ACR criteria for SLE; not completed high school; older age; single marital status; a lower household income; longer disease duration; higher SLICC Damage Index and SLAM scores; lower SF-36 PCS and SF-36 MCS scores; less vigorous activity per week; and fibromyalgia, arthralgias, fatigue and depression (p < 0.05). This contemporary rate of WD is lower than many past reports. Socio-demographic factors, co-morbidities (fibromyalgia and fatigue) and disease related factors were strongly associated with WD. We cannot determine cause and effect as the study was cross-sectional. Lupus (2009) 18, 1281—1288.

The relationship between race, cigarette smoking and carotid intimal medial thickness in systemic lupus erythematosus

Scalzi, L., Bhatt, S., Gilkeson, R., Shaffer, M. — Tue, 24 Nov 2009 08:56:19 PST

Racial differences are known to account for a higher incidence of systemic lupus erythematosus (SLE), as well as increased disease severity and mortality. The purpose of this study was to determine whether there are any race-specific risk factors that affect measures of subclinical atherosclerosis in SLE patients. Traditional and SLE-related cardiovascular disease (CVD) risk factors were assessed in 106 female SLE patients. Carotid medial intimal medial thickness (mIMT) and coronary artery calcification (CAC) were measured on all subjects. Differences were evaluated between races for all clinical, serologic, and CVD risk factors and the racial interactions with all covariables. Outcomes included mIMT and CAC. There were no significant differences between races with regard to mIMT or CAC. Significant covariables in the final model for mIMT included age, triglycerides, glucose, and race—age and race—smoking interactions. A prediction model with fixed significant covariables demonstrated that Black subjects with a smoking history had a significantly higher mIMT than Blacks who had never smoked, an effect not seen in Whites. There were no differences between having CAC or with the CAC scores between the races. In the final model for CAC, age and SLE disease duration were significant covariables impacting CAC. When controlling for other significant CVD covariables and interactions, Black women, but not White, with SLE with a history of smoking have higher mIMT measurements than those who have never smoked. This is the first report documenting the race-specific effect of smoking on subclinical measures of CVD in SLE. Lupus (2009) 18, 1289—1297.

An analysis of joint replacement in patients with systemic lupus erythematosus

Mourao, A., Amaral, M., Caetano-Lopes, J., Isenberg, D. — Tue, 24 Nov 2009 08:56:19 PST

A small but important group of patients in our lupus cohort has needed total joint replacement (TJR). Arthritis was identified in 94% of our lupus patients. We have determined how many of our patients needed TJR, explored the risk factors for this procedure in patients with SLE and reviewed the outcome for these patients. Records of the cohort of patients with SLE who have attended our lupus clinic at University College of London Hospital/Middlesex from 1978 to 2008 were reviewed and patients who underwent TJR were identified. We recorded demographic data, other major systemic manifestations of SLE, autoantibody profile, previous use of steroids, other major systemic illnesses, smoking and alcohol habits. Nineteen patients with SLE from our cohort of 500 were found to have at least one TJR. Avascular necrosis (AVN) or concomitant rheumatoid arthritis (RA) was present in the majority of these patients. In contrast, age at disease onset, the presence of anti-cardiolipin antibodies, Raynaud’s phenomenon and smoking habits were not found to be contributing factors for the need to replace joints. Four of our 19 patients (21.1%) had complications of the joint replacement: two of them had infections of the replaced joint, one had a large haematoma immediately after the surgery requiring surgical evacuation and the other had a deep vein thrombosis. None of the patients so far has required joint re-replacement. In conclusion, 4% of SLE patients in our cohort have one or more joints replaced, the majority because of AVN or RA. Lupus (2009) 18, 1298—1302.

Peripheral vascular damage in systemic lupus erythematosus: data from LUMINA, a large multi-ethnic U.S. cohort (LXIX)

Burgos, P., Vila, L., Reveille, J., Alarcon, G. — Tue, 24 Nov 2009 08:56:19 PST

To determine the factors associated with peripheral vascular damage in systemic lupus erythematosus patients and its impact on survival from Lupus in Minorities, Nature versus Nurture, a longitudinal US multi-ethnic cohort. Peripheral vascular damage was defined by the Systemic Lupus International Collaborating Clinics Damage Index (SDI). Factors associated with peripheral vascular damage were examined by univariable and multi-variable logistic regression models and its impact on survival by a Cox multi-variable regression. Thirty-four (5.3%) of 637 patients (90% women, mean [SD] age 36.5 [12.6] [16—87] years) developed peripheral vascular damage. Age and the SDI (without peripheral vascular damage) were statistically significant (odds ratio [OR] = 1.05, 95% confidence interval [CI] 1.01—1.08; P = 0.0107 and OR = 1.30, 95% CI 0.09—1.56; P = 0.0043, respectively) in multi-variable analyses. Azathioprine, warfarin and statins were also statistically significant, and glucocorticoid use was borderline statistically significant (OR = 1.03, 95% CI 0.10—1.06; P = 0.0975). In the survival analysis, peripheral vascular damage was independently associated with a diminished survival (hazard ratio = 2.36; 95% CI 1.07—5.19; P = 0.0334). In short, age was independently associated with peripheral vascular damage, but so was the presence of damage in other organs (ocular, neuropsychiatric, renal, cardiovascular, pulmonary, musculoskeletal and integument) and some medications (probably reflecting more severe disease). Peripheral vascular damage also negatively affected survival. Lupus (2009) 18, 1303—1308.

Gigantomastia in a patient with systemic lupus erythematosus successfully treated by reduction mammoplasty

Lanzon, A., Navarra, S. — Tue, 24 Nov 2009 08:56:19 PST

The objective of the study was to describe a Filipino woman with systemic lupus erythematosus (SLE) who developed gigantomastia associated with hyperoestrogenemia and successfully treated by reduction mammoplasty. A 37-year-old Filipino woman with SLE of 5-year duration presented with enlargement of breasts, which became more noticeable and progressive during disease flares requiring increased steroid dose (±40 mg/day). Following control of the last SLE flare, with prednisone effectively tapered to 15 mg/day, she consented to surgical breast reduction. Preoperative physical examination recorded the right and left breast measurement of 61 cm and 54.5 cm from sternal notch to nipple tip, respectively. serum oestrogen assay was elevated. She successfully underwent reduction mammoplasty with free nipple graft, with an uneventful postoperative course. The breast tissue oestrogen and progesterone receptor assays were strongly positive. In the succeeding months, SLE disease remained stable with prednisone tapered to 10 mg daily. This case illustrates a rare occurrence of gigantomastia associated with hyperoestrogenemia in a patient with SLE, successfully treated with reduction mammoplasty. Lupus (2009) 18, 1309—1312.

Ovarian necrotizing vasculitis in a patient with lupus

Tue, 24 Nov 2009 08:56:19 PST

Ovarian vasculitis is a rare complication seen in the reproductive system and has been described in only one patient with lupus and a few patients with other rheumatic conditions (polyarteritis nodosa, giant cell arteritis, scleroderma). Three additional cases following gynecology procedures have also been reported. We report the second case of a patient with systemic lupus erythematosus, who developed ovarian vasculitis. The diagnosis was made at the age of 12 and confirmed by laparoscopy and histopathology in the presence of disease activity. She experienced late menarche at the age of 16, and she experienced a good clinical evolution after disease treatment with regular menstrual cycles and normal levels of sexual hormones. Lupus (2009) 18, 1313—1315.

Limbic encephalitis associated with systemic lupus erythematosus

Tue, 24 Nov 2009 08:56:20 PST

A 34-year-old woman with systemic lupus erythematosus (SLE) presented with general fatigue, seizures and memory loss. Magnetic resonance imaging of the brain showed a high signal area in the mesial temporal lobe bilaterally. Computed tomography scan of the chest and abdomen and ultrasound of pelvis detected no malignancy and tumour marker, antibodies to antineuronal antibodies (anti-Hu, anti-Ta and anti-Ma) and antibodies to voltage-gated potassium channels were all negative. The present case is limbic encephalitis (LE) associated with SLE and the pathogenesis may include autoimmunity shared. Our experience indicates that the immunologic spectrum of LE will expand to include additional immune mechanisms. Lupus (2009) 18, 1316—1319.

A clinical and epidemiological study of lupus erythematosus at a tertiary referral dermatology clinic in Korea

Bae, Y., Yun, S-J., Lee, J-B., Kim, S-J., Won, Y., Lee, S-C. — Tue, 24 Nov 2009 08:56:20 PST

Dermatological examination is critical for the evaluation of lupus erythematosus. However, little is known about the epidemiology and clinical characteristics of the lupus erythematosus patients that visit dermatology clinics with the chief complaint of skin lesions, especially among Asian populations. We performed this study to determine the epidemiology of cutaneous lupus erythematosus for three subtypes: acute cutaneous lupus erythematosus, subacute cutaneous lupus erythematosus, and chronic cutaneous lupus erythematosus, and for lupus erythematosus non-specific skin disease. Also, we sought to determine the relationship between each type of lupus erythematosus, by the skin manifestations and systemic lupus erythematosus. The medical records of lupus erythematosus patients that were diagnosed by their clinical manifestations, skin biopsy results, and laboratory findings from January 1998 through December 2007 were reviewed. A total of 117 patients were diagnosed with lupus erythematosus; 62 cases had chronic cutaneous lupus erythematosus, 11 had subacute cutaneous lupus erythematosus, and 41 had acute cutaneous lupus erythematosus. The remaining three had systemic lupus erythematosus features with lupus erythematosus non-specific skin lesions such as Raynaud phenomenon, livedo reticularis/vasculitis, non-scarring alopecia, and periungual telangiectasia. The acute cutaneous lupus erythematosus subgroup showed extreme female predominance (9.2:1) whereas subacute and chronic cutaneous lupus erythematosus subgroups did not. Patients with chronic cutaneous lupus erythematosus tended to be older than other groups (peak incidence in the fifth decade). Incidence of laboratory abnormalities, including positive connective tissue markers such as antinuclear, double-strand DNA, and Ro/SS-A antibodies, were present in the order acute, subacute, and chronic cutaneous lupus erythematosus. Acute cutaneous lupus erythematosus almost always indicated systemic involvement of lupus erythematosus, whereas chronic cutaneous lupus erythematosus did not predict the development or existence of systemic lupus erythematosus and had a benign clinical course. Careful consideration of lupus erythematosus non-specific skin lesions may help detect systemic lupus erythematosus regardless of the diagnosis of cutaneous lupus erythematosus. Lupus (2009) 18, 1320—1326.

Abnormal expression pattern of histone demethylases in CD4 + T cells of MRL/lpr lupus-like mice

Long, H., Huang, W., Yin, H., Zhao, S., Zhao, M., Lu, Q. — Tue, 24 Nov 2009 08:56:20 PST

Interleukin-6 release from peripheral mononuclear cells is associated to disease activity and treatment response in patients with lupus nephritis

Esposito, P., Balletta, M. M, Procino, A., Postiglione, L., Memoli, B. — Tue, 24 Nov 2009 08:56:20 PST

Protein-losing enteropathy with mesenteric venous thrombosis: a forme fruste of systemic lupus erythematosus

Chen, W.-L., Tsao, Y.-T. — Tue, 24 Nov 2009 08:56:20 PST

Efalizumab for subacute cutaneous lupus: report of two different outcomes

Tue, 24 Nov 2009 08:56:20 PST

Ovarian vasculitis in an adult with fatal systemic lupus erythematosus

Tue, 24 Nov 2009 08:56:20 PST

Infections, vaccines and autoimmunity

Shoenfeld, Y. — Fri, 30 Oct 2009 07:18:45 PDT

Infectious antibodies in systemic lupus erythematosus patients

Fri, 30 Oct 2009 07:18:45 PDT

Infections can act as environmental triggers that induce or promote systemic lupus erythematosus (SLE) in genetically predisposed individuals. New technologies, developed recently, enable simultaneous assessment of multiple antibodies. Antibodies to specific infectious agents may shed light into the mechanisms of induction of SLE. The aim of this study was to investigate the prevalence of seropositivity and the titers of antibodies to bacterial, viral, and parasitic agents in SLE patients compared with non-autoimmune controls. Sera from 260 individuals (120 SLE patients and 140 controls) were tested by the BioPlex 2200 Multiplexed Immunoassay method (BioRad) for the prevalence and titers of antibodies to eight infectious agents (Epstein—Barr virus: early antigen IgG, nuclear antigen IgG, viral capsid antigen IgG and IgM, heterophile IgM; cytomegalovirus IgG and IgM; Toxoplasma gondii IgG and IgM; rubella IgG and IgM; Treponema pallidum TPr15G, TPr17G, TPr47G; herpes simplex virus type 1 and 2 IgG; hepatitis C virus and hepatitis B core antibodies. Cytomegalovirus IgM and Epstein—Barr virus early antigen IgG (but not other Epstein—Barr virus antigens) were significantly more prevalent in SLE patients than in controls. Conversely, positive titers of hepatitis B core and rubella IgG antibodies were less prevalent in the SLE patients than in controls. Other differences in titer positivity prevalence were not detected between patients and controls. The titers of the cytomegalovirus IgM, Toxoplasma IgG, Epstein—Barr virus early antigen, and viral capsid antigen IgG antibodies were significantly higher in SLE compared with controls. Our data suggest the importance of previous exposure to infectious agents in the induction and the prevention of SLE. Lupus (2009) 18, 1129—1135.

Cross-talk of the environment with the host genome and the immune system through endogenous retroviruses in systemic lupus erythematosus

Blank, M., Shoenfeld, Y., Perl, A. — Fri, 30 Oct 2009 07:18:45 PDT

Environmental factors are capable of triggering the expression of human endogenous retroviruses and induce an autoimmune response. Infection can promote the expression of human endogenous retroviruses by molecular mimicry or by functional mimicry. There are additional mechanisms which may control the expression of human endogenous retroviruses, such as epigenetic status of the genome (hypomethylation, histone deacetylation). Ultraviolet exposure, chemicals/drugs, injury/stress, hormones, all as a single cause or in a concert, may modulate the involvement of human endogenous retroviruses in pathogenic processes. In the current review we summarize the current knowledge on infections, molecular mimicry, cross-reactivity and epigenetics contribution for trigger human endogenous retroviruses expression and pathogenesis in lupus patients. Lupus (2009) 18, 1136—1143.

Parasitic infection and autoimmunity

Zandman-Goddard, G., Shoenfeld, Y. — Fri, 30 Oct 2009 07:18:45 PDT

Systemic lupus erythematosus is the prototypic multi-system autoimmune disease characterized by the production of multiple autoantibodies. The development of disease depends on a genetic predisposition and exposure to environmental factors including UV light, drugs, and infections. The association of parasitic infection and the development of autoimmune disease in general and lupus in particular remains elusive. In this paper, we review the recent evidence for protection from autoimmunity by parasites, models of parasite-related autoimmunity, molecular mimicry, the impact of parasitic molecules on the immune response and the association between parasitic load and the degree of autoimmunity.

Common infectious agents prevalence in antiphospholipid syndrome

Fri, 30 Oct 2009 07:18:45 PDT

Antiphospholipid syndrome is characterized by thrombosis and pregnancy loss. Infections are generally associated with autoimmune diseases, but in the setting of antiphospholipid syndrome this link has been suggested as having a pathogenic role. In this study, 98 patients with antiphospholipid syndrome were screened for antibodies directed to several infectious agents. The main finding in this study is the significantly higher prevalence of IgM antibodies to toxoplasma and rubella. This novel finding suggests that these infections might be associated with antiphospholipid syndrome. As autoimmune diseases and, in particular, antiphospholipid syndrome are associated with infections, mainly the catastrophic type of the syndrome, this finding implies that a current infection with these agents, i.e. toxoplasma and rubella, might either be related to the pathogenesis of antiphospholipid syndrome or alternatively to its manifestations. Lupus (2009) 18, 1149—1153.

Regulation of cellular immunity prevents Helicobacter pylori-induced atherosclerosis

Fri, 30 Oct 2009 07:18:45 PDT

Helicobacter pylori (H. pylori) is a predominant pathogen that causes not only gastroduodenal diseases but also extra-alimentary tract diseases. In this study, we demonstrated that H. pylori infection promoted atherogenesis in heterozygous apoe^{+/ –-}ldlr^+/–-mice. The male mice were fed with high fat diet from the age of 6 weeks. At the age of 16 weeks, development of atherosclerotic lesions was observed in the H. pylori-infected mice, and it seemed to be associated with an elevation of Th1-immune response against H. pylori origin-heat shock protein 60 (Hp-HSP60) and an increment of transendothelial migration of T cells. Subcutaneous immunisation with Hp-HSP60 or H. pylori eradication with antibiotics significantly reduced the progression of atherosclerosis, accompanied by a decline of Th1 differentiation and reduction of their chemotaxis beyond the endothelium. Thus, oral infection with H. pylori accelerates atherosclerosis in mice and the active immunisation with Hp-HSP60 or the eradication of H. pylori with antibiotics can moderate/prevent cellular immunity, resulting in a reduction of atherosclerosis. Lupus (2009) 18, 1154—1168.

Infection--genetics relationship in systemic lupus erythematosus

Sebastiani, G. D., Galeazzi, M. — Fri, 30 Oct 2009 07:18:45 PDT

Genetic, environmental, and hormonal factors contribute to disease susceptibility in systemic lupus erythematosus. Among environmental factors, infectious agents play a major role. When considering the complex relationship between genetic predisposition and infections in the pathogenesis of systemic lupus erythematosus, we have to consider that infectious agents can interact with the immune system in several ways. For example, molecular mimicry, altered apoptosis of the host cells, exposure of as yet masked antigens to the immune system by a given microorganism, and direct viral invasion of immunocompetent cells are all mechanisms that may give rise to dysfunction of the immune system; in addition, some genetically determined deficit of the immune system, such as complement deficiency or deficit of mannose binding lectine, may cause insufficient clearance of infectious agents, whose persistence in the host may determine autoimmunity. Finally, evidence has been emerging suggesting that the production of autoantibodies, by infected B-lymphocytes, may be drawn by altered expression of particular microRNA in these cells. In this paper, we review some of the distinct scenarios that can account for the role of infectious agents, acting on a genetically prone host, in determining systemic lupus erythematosus.

Antibodies to DNA: infection or genetics?

Pisetsky, D., Vrabie, I. — Fri, 30 Oct 2009 07:18:45 PDT

Antibodies to DNA (anti-DNA) are the serological hallmark of systemic lupus erythematosus (SLE) and unique markers of the immunological disturbances critical to disease pathogenesis. In the form of immune complexes, anti-DNA autoantibodies can deposit in the tissue to incite inflammation and damage; in addition, these complexes can induce cytokine production, most prominently, type 1 interferon. Studies in both patients and animal models have implicated genetic as well as environmental factors in the aetiology of the anti-DNA response. Because bacterial DNA is a potent stimulant of innate immunity by both toll-like receptor (TLR) and non-TLR signalling pathways, foreign DNA introduced during the course of bacterial or viral infection could have a dual role in antibody induction. This DNA could serve as an adjuvant to activate innate immunity as well as an immunogen to drive an antigen-specific antibody response. In this scenario, the generation of cross-reactive autoantibodies, in contrast to highly specific antibodies to bacterial DNA, most likely depends on genetically determined abnormalities in the B-cell repertoire in patients with SLE. Given the universal expression of DNA, this model suggests that many different kinds of infections could trigger pathogenic autoantibody responses in SLE, as well as induce flare.

Molecular mimicry in systemic lupus erythematosus

Agmon-Levin, N., Blank, M., Paz, Z., Shoenfeld, Y. — Fri, 30 Oct 2009 07:18:45 PDT

Systemic lupus erythematosus is a multi-systemic autoimmune disease distinguished by the presence of various autoantibodies. Like most autoimmune diseases, systemic lupus erythematosus is believed to be induced by a combination of genetic, immunologic, and environmental factors, mainly infectious agents. Molecular mimicry between an infectious antigen and self-components is implicated as a pivotal mechanism by which autoimmune diseases such as systemic lupus erythematosus are triggered. Here we review the current evidence of molecular mimicry between different infectious agents and systemic lupus erythematosus.

Vaccination of healthy subjects and autoantibodies: from mice through dogs to humans

Toplak, N., Avcin, T. — Fri, 30 Oct 2009 07:18:45 PDT

Vaccination against pathogenic microorganisms is one of the major achievements of modern medicine, but due to an increasing number of reports of adverse reactions the vaccination procedure has induced also considerable debate. It is well known that certain infections are involved in triggering the production of autoantibodies, which could lead to autoimmune adverse reactions in genetically predisposed subjects. Based on these findings it was assumed that vaccinations might induce similar autoimmune reactions. At present there is no clear-cut evidence that vaccinations are associated with overt autoimmune diseases but it has been demonstrated that in genetically predisposed persons vaccination can trigger the production of autoantibodies and autoimmune adverse reactions. The first studies investigating the production of autoantibodies following vacination were done in dogs and mice. Several studies investigated the production of autoantibodies following vaccination in patients with autoimmune diseases, but there are only limited data on the autoimmune responses after vaccinations in apparently healthy humans. This review summarizes current evidence on the vaccinationinduced autoantibodies in apparently healthy subjects including studies in animals and humans.

Ten cases of systemic lupus erythematosus related to hepatitis B vaccine

Fri, 30 Oct 2009 07:18:45 PDT

The objective of this article is to identify common and atypical features of systemic lupus erythematosus diagnosed following hepatitis B vaccination. We analyzed retrospectively the medical records of 10 systemic lupus erythematosus patients from different centers, who developed the disease following hepatitis B vaccination and determined the prevalence of different manifestations and the time association to vaccination. In this case series, 80% of the patients were female, mean age 35 ± 9 years, of which 20% received one inoculation, 20% received two doses and 60% received all three inoculations. The mean latency period from the first hepatitis B virus immunization and onset of autoimmune symptoms was 56.3 days. All patients were diagnosed with systemic lupus erythematosus, according to the American College of Rheumatology revised criteria within 1 year. The prevalence of some systemic lupus erythematosus manifestations was typical and included involvement of the joints (100%), skin (80%), muscles (60%) and photosensitivity (30%). Other symptoms differed in this unique group of systemic lupus erythematosus patients such as low rate of kidney and hematologic involvement, and a relatively high rate of hepatitis (20%). Neurological (80%) and pulmonary (70%) symptoms were also common in this group. Data from this case-series, and previously documented cases in the literature could only show a temporal relation between hepatitis B vaccination and the appearance of systemic lupus erythematosus. Systemic lupus erythematosus related to vaccine may differ from idiopathic systemic lupus erythematosus in its clinical presentation and may resemble drug-induced systemic lupus erythematosus. Thus, physicians should be alerted to this potential association, its possible long latency period and unique presentations, and be encouraged to report and analyze these cases. Lupus (2009) 18, 1192—1197.

Transverse myelitis and vaccines: a multi-analysis

Agmon-Levin, N., Kivity, S., Szyper-Kravitz, M., Shoenfeld, Y. — Fri, 30 Oct 2009 07:18:45 PDT

Transverse myelitis is a rare clinical syndrome in which an immune-mediated process causes neural injury to the spinal cord. The pathogenesis of transverse myelitis is mostly of an autoimmune nature, triggered by various environmental factors, including vaccination. Our aim here was to search for and analyze reported cases of transverse myelitis following vaccination. A systematic review of PubMed, EMBASE and DynaMed for all English-laguage journals published between 1970 and 2009 was preformed, utilizing the key words transverse myelitis, myelitis, vaccines, post-vaccination, vaccination and autoimmunity. We have disclosed 37 reported cases of transverse myelitis associated with different vaccines including those against hepatitis B virus, measles—mumps—rubella, diphtheria—tetanus—pertussis and others, given to infants, children and adults. In most of these reported cases the temporal association was between several days and 3 months, although a longer time frame of up to several years was also suggested. Although vaccines harbor a major contribution to public health in the modern era, in rare cases they may be associated with autoimmune phenomena such as transverse myelitis. The associations of different vaccines with a single autoimmune phenomenon allude to the idea that a common denominator of these vaccines, such as an adjuvant, might trigger this syndrome. Lupus (2009) 18, 1198—1204.

Safety of vaccination of patients with systemic lupus erythematosus

Abu-Shakra, M. — Fri, 30 Oct 2009 07:18:46 PDT

Live vaccines are not safe for immuno-compromised patients and should not be given to patients with systemic lupus erythematosus. In addition, all vaccines are not recommended for systemic lupus erythematosus patients when their disease is very active and mainly for patients with very active lupus nephritis. Systemic lupus erythematosus patients with quiescent or mildly active disease should be encouraged to receive vaccination according the recommendations given by the Immunization Practices Advisory Committee. Among this group of systemic lupus erythematosus patients, vaccines are safe and they do not affect the clinical manifestations of systemic lupus erythematosus including renal features, disease activity, or the requirement for steroids or cytotoxic drugs. However, vaccines may trigger the generation of autoantibodies which is usually short term and has no clinical significance. In individual cases vaccines exacerbate systemic lupus erythematosus; however, no specific clinical or laboratory variables have been identified to be associated with flare of systemic lupus erythematosus following vaccination. Lupus (2009) 18, 1205—1208.

Vaccination, atherosclerosis and systemic lupus erythematosus

Carvalho, J., Pereira, R., Shoenfeld, Y. — Fri, 30 Oct 2009 07:18:46 PDT

Atherosclerosis is an inflammatory disease, leading to the formation of pro-inflammatory and pro-oxidative lipids that generate an immune response. Several antigens have been shown to activate the immune response and affect the development of atherogenesis. Systemic lupus erythematosus is an autoimmune and inflammatory disease strongly associated with premature development of atherosclerotic plaques. Modulation of the immune system could represent a useful approach to prevent and/or treat atherosclerosis. A vaccination-based approach might be a useful, effective tool in the modern arsenal of cardiovascular therapies and could be used on a large scale at a low cost. In non-systemic lupus erythematosus populations, vaccines against oxidized low-density lipoprotein, beta-2-glycoprotein I, heat shock proteins, lipoproteins, cholesterol, molecules involved in cholesterol metabolism, and other molecules (CD99, vascular endothelial growth factor-receptor, and interleukin-2) have been tested, with promising results. However, there are no studies of vaccination against atherosclerosis in systemic lupus erythematosus. Lupus (2009) 18, 1209—1212.

Vaccines as a trigger for myopathies

Orbach, H., Tanay, A. — Fri, 30 Oct 2009 07:18:46 PDT

Vaccines are considered to be among the greatest medical discoveries, credited with the virtual eradication of some diseases and the consequent improved survival and quality of life of the at-risk population. With that, vaccines are among the environmental factors implicated as triggers for the development of inflammatory myopathies. The sporadic reports on vaccineinduced inflammatory myopathies include cases of hepatitis B virus, bacillus Calmette—Guérin, tetanus, influenza, smallpox, polio, diphtheria, diphtheria—pertussis—tetanus, combination of diphtheria with scarlet fever and diphtheria—pertussis—tetanus with polio vaccines. However, a significant increase in the incidence of dermatomyositis or polymyositis after any massive vaccination campaign has not been reported in the literature. In study patients with inflammatory myopathies, no recent immunization was recorded in any of the patients. Moreover, after the 1976 mass flu vaccination, no increase in the incidence of inflammatory myopathies was observed. Although rare, macrophagic myofasciitis has been reported following vaccination and is attributed to the aluminium hydroxide used as an adjuvant in some vaccines. Prospective multicenter studies are needed to identify potential environmental factors, including vaccines, as potential triggers for inflammatory myopathies. Lupus (2009) 18, 1213—1216.

Adjuvants and autoimmunity

Israeli, E., Agmon-Levin, N., Blank, M., Shoenfeld, Y. — Fri, 30 Oct 2009 07:18:46 PDT

Some adjuvants may exert adverse effects upon injection or, on the other hand, may not trigger a full immunological reaction. The mechanisms underlying adjuvant adverse effects are under renewed scrutiny because of the enormous implications for vaccine development. In the search for new and safer adjuvants, several new adjuvants were developed by pharmaceutical companies utilizing new immunological and chemical innovations. The ability of the immune system to recognize molecules that are broadly shared by pathogens is, in part, due to the presence of special immune receptors called toll-like receptors (TLRs) that are expressed on leukocyte membranes. The very fact that TLR activation leads to adaptive immune responses to foreign entities explains why so many adjuvants used today in vaccinations are developed to mimic TLR ligands. Alongside their supportive role, adjuvants were found to inflict by themselves an illness of autoimmune nature, defined as ‘the adjuvant diseases’. The debatable question of silicone as an adjuvant and connective tissue diseases, as well as the Gulf War syndrome and macrophagic myofaciitis which followed multiple injections of aluminium-based vaccines, are presented here. Owing to the adverse effects exerted by adjuvants, there is no doubt that safer adjuvants need to be developed and incorporated into future vaccines. Other needs in light of new vaccine technologies are adjuvants suitable for use with mucosally delivered vaccines, DNA vaccines, cancer and autoimmunity vaccines. In particular, there is demand for safe and non-toxic adjuvants able to stimulate cellular (Th1) immunity. More adjuvants were approved to date besides alum for human vaccines, including MF59 in some viral vaccines, MPL, AS04, AS01B and AS02A against viral and parasitic infections, virosomes for HBV, HPV and HAV, and cholera toxin for cholera. Perhaps future adjuvants occupying other putative receptors will be employed to bypass the TLR signaling pathway completely in order to circumvent common side effects of adjuvant-activated TLRs such as local inflammation and the general malaise felt because of the costly whole-body immune response to antigen. Lupus (2009) 18, 1217—1225.

Silicone breast implantation-induced scleroderma: description of four patients and a critical review of the literature

Levy, Y., Rotman-Pikielny, P., Ehrenfeld, M., Shoenfeld, Y. — Fri, 30 Oct 2009 07:18:46 PDT

Since the early 1980s, case reports and case series describe an association between silicon breast implants and the appearance of autoimmune diseases, particularly scleroderma. The publication of those cases led to a large number of studies to investigate this association. The conclusion of those studies is that most probably there has not been an increased incidence of autoimmune diseases in women with silicon breast implants. Nevertheless, the US Food and Drug Administration determined that silicone gel breast implants are not completely safe, only that they are ‘reasonably safe.’ The debate continues regarding this association. In this article we present new cases of silicon breast implant-induced scleroderma and review the literature on this subject. Lupus (2009) 18, 1226—1232.

Pathogenic role of anti-endothelial cell antibodies in autoimmune rheumatic diseases

Domiciano, D., Carvalho, J., Shoenfeld, Y. — Fri, 30 Oct 2009 07:18:46 PDT

Anti-endothelial cells antibodies have been detected in numerous autoimmune and inflammatory diseases, including systemic lupus erythematous, rheumatoid arthritis, vasculitis and sarcoidosis. Anti-endothelial cells antibodies bind to endothelial cell antigens and induce endothelial damage. Their effects on the endothelial cell have been considered responsible, at least in part, by the vascular injury which occurs in these pathological conditions.

Drug-induced lupus: an update on its dermatologic aspects

Marzano, A., Vezzoli, P, Crosti, C — Thu, 17 Sep 2009 02:33:30 PDT

Drug-induced lupus erythematosus (DILE) is defined as an entity characterized by clinical manifestations and immunopathological serum findings similar to those of idiopathic lupus but which is temporally related to continuous drug exposure and resolves after discontinuation of the offending drug. Similar to idiopathic lupus, DILE can be divided into systemic lupus erythematosus (SLE), subacute cutaneous lupus erythematosus (SCLE) and chronic cutaneous lupus erythematosus (CCLE). Based on the literature review and retrospective analysis of our case series, we focused on the dermatological aspects of DILE. The cutaneous features of drug-induced SLE are protean, including particularly purpura, erythema nodosum and photosensitivity as well as the skin lesions characterizing both urticarial and necrotizing vasculitis. The typical laboratory profile of systemic DILE consists of positive antinuclear antibodies (ANA) and antihistone antibodies, the latter being regarded as the serum marker of this subset. The drugs most frequently implicated in the development of systemic DILE are hydralazine, procainamide, isoniazid and minocycline. Drug-induced SCLE usually presents with annular polycyclic or papulosquamous cutaneous manifestations as in the idiopathic form, but blisters or targetoid lesions mimicking erythema multiforme cannot rarely be associated. The clinical presentation is often generalized, with involvement of the lower legs that are usually spared in idiopathic SCLE. ANA and anti-Ro/SSA antibodies are usually present, whereas antihistone antibodies are uncommonly found. Drugs associated with SCLE include particularly calcium channel blockers, angiotensin-converting enzyme inhibitors, thiazide diuretics, terbinafine and the recently reported tumour necrosis factor (TNF)- antagonists. Drug-induced CCLE is very rarely described in the literature and usually refers to fluorouracile agents or TNF- antagonists. The picture is characterized by the occurrence of classic discoid lesions, but aspects of lupus tumidus can occasionally develop. ANA are demonstrated in around two-thirds of the cases. Management of DILE is based on the withdrawal of the offending drug. Topical and/or systemic corticosteroids and other immunosuppressive agents should be reserved for resistant cases.

Effects of chronic exposure to DDT and TCDD on disease activity in murine systemic lupus erythematosus

Li, J, McMurray, R. — Thu, 17 Sep 2009 02:33:30 PDT

Oestrogens contribute to the female preponderance of autoimmune diseases such as systemic lupus erythematosus (SLE). Environmental xenoestrogens superimposed upon endogenous pituitary-gonadal axis may affect the development of autoimmunity. This study examined the effects of chronic exposure to xenoestrogens – o,p’-dichlorodiphenyltrichloroethane (DDT) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on disease activity in the New Zealand Black/New Zealand White F1 hybrid (B/W) mouse model of SLE. Intact female mice had repeatedly received injections of DDT, TCDD or control vehicle since 6 weeks of age. Weight change, albuminuria, mortality, relevant immunological and histological parameters were assessed. DDT exposure markedly increased the incidence of albuminuria and reduced uterine weight but had no measured effects on immunity or mortality in this study. TCDD-exposed mice had significantly lower incidence of albuminuria, serum anti-DNA antibody and total IgG levels, and mortality compared to controls. Also, TCDD group had significantly lower thymic and splenic weights, decreased percentages of CD4⁺CD8⁺ thymocytes and splenic CD4⁺ T cells, increased percentage of splenic B220⁺sIgM⁺ B cells and higher serum interferon gamma concentration. Taken together, DDT exposure appeared to accelerate the development of albuminuria in lupus-prone mice. TCDD was immunosuppressive to murine SLE. Xenoestrogens may have compound- and tissue-specific effects that require further elucidation in future work.

Colour Doppler ultrasound of the ocular circulation in patients with systemic lupus erythematosus identifies altered microcirculatory haemodynamics

Thu, 17 Sep 2009 02:33:30 PDT

We assessed whether quantitative analysis of Doppler flow velocity waveforms is able to identify subclinical microvascular abnormalities in SLE and whether eigenvector analysis can detect changes not detectable using the resistive index (RI). Fifty-four SLE patients with no conventional cardiovascular risk factors, major organ involvement or retinopathy were compared to 32 controls. Flow velocity waveforms were obtained from the ophthalmic artery (OA), central retinal artery (CRA) and common carotid artery (CA). The waveforms were analysed using eigenvector decomposition and compared between groups at each arterial site. The RI was also determined. The RI was comparable between groups. In the OA and CRA, there were significant differences in the lower frequency sinusoidal components (P < 0.05 for each component). No differences were apparent in the CA between groups. Eigenvector analysis of Doppler flow waveforms, recorded in proximity of the terminal vascular bed, identified altered ocular microvascular haemodynamics in SLE. Altered waveform structure could not be identified by changes in RI, the traditional measure of downstream vascular resistance. This analytical approach to waveform analysis is more sensitive in detecting preclinical microvascular abnormalities in SLE. It may hold potential as a useful tool for assessing disease activity, response to treatment, and predicting future vascular complications.

Factors Associated with Arterial Vascular Events in PROFILE: A Multiethnic Lupus Cohort

Thu, 17 Sep 2009 02:33:30 PDT

The objective of this study was to determine the factors associated with the occurrence of arterial vascular events in a multiethnic systemic lupus erythematosus (SLE) cohort. The PROFILE cohort, comprised SLE patients (n = 1333) of defined ethnicity from five different US institutions, was studied to determine demographic, clinical and biological variables associated with vascular events. An arterial vascular event (first episode) was either a myocardial infarction, angina pectoris and/or a vascular procedure for myocardial infarction, stroke, claudication and/or evidence of gangrene. Patient characteristics were analyzed by univariable and multivariable Cox proportional hazards regression analyses. One-hundred twenty-three (9.8%) patients had at least one incident arterial event. Age at cohort enrollment (HR = 1.04, 95% CI 1.03–1.06), smoking (HR = 2.20, 95% CI 1.40–3.46) and the CRP2* C alleles (HR = 1.91, 95% CI 1.04–3.49) were associated with a shorter time-to-the occurrence of arterial vascular events. Some clinical manifestations of disease activity were associated with a shorter time-to-occurrence [psychosis (HR = 2.21, 95% CI 1.10–4.44), seizures (HR = 1.85, 95% CI 1.00–3.24) and anaemia (HR = 1.83, 95% CI 1.02–3.31)], but others were not [arthritis (HR = 0.32, 95% CI 0.18–0.58)]. In conclusion, older patients, especially in the context of a predisposing environmental factor (smoking) and severe clinical manifestations, are at higher risk of having arterial vascular events. The genetic contribution of the variation at the CRP locus was not obscured by demographic or clinical variables. Awareness of these factors should lead to more effective management strategies of patients at risk for arterial vascular events.

Variability and correlates of high sensitivity C-reactive protein in systemic lupus erythematosus

Nikpour, M, Gladman, D., Ibanez, D, Urowitz, M. — Thu, 17 Sep 2009 02:33:30 PDT

In the general population, high-sensitivity C-reactive protein (hsCRP), a marker of inflammation, is relatively stable over time and independently predicts cardiovascular events. Systemic lupus erythematosus (SLE), a chronic inflammatory disease, is strongly associated with coronary artery disease (CAD). The objective of this study was to determine the variability and correlates of hsCRP in patients with SLE. Two cohorts from the University of Toronto Lupus Clinic, one with newly diagnosed and the other with prevalent SLE for 4 or more years, were selected. HsCRP was measured on serially collected samples, and hsCRP levels were ranked according to quartiles of cardiovascular risk. Correlates of hsCRP were determined using multivariate regression modelling with analysis of repeated measures. Among 58 patients in the inception cohort, over time, 36 (62%) moved from one hsCRP risk quartile to another. Among 414 patients in the prevalent cohort, 294 (71.0%) moved from one risk quartile to another. In both cohorts, within-patient variance comprised the majority of total variance in hsCRP levels. In multivariate regression analysis, hsCRP increased with age (P = 0.002), postmenopausal status (P = 0.03), smoking (P = 0.007) and presence of infection (P = 0.0001) and decreased with use of immunosuppressives (P = 0.02). There is marked variability of hsCRP level over time in SLE, regardless of disease duration. This variability is due to age and SLE treatment, menopausal status, smoking and the occurrence of infection. The variability of hsCRP in SLE casts doubt over its usefulness as an independent predictor of CAD risk in this disease and potentially in other chronic inflammatory diseases.

Association of TNF-{alpha} gene polymorphisms with systemic lupus erythematosus in Taiwanese patients

Thu, 17 Sep 2009 02:33:30 PDT

Tumour necrosis factor- (TNF-), an important proinflammatory cytokine, exerts a variety of physiological and pathogenic effects that lead to tissue destruction. Studies on the association of TNF- genetic polymorphisms with systemic lupus erythematosus (SLE) have yielded inconclusive results. We investigated the association of TNF- genetic polymorphisms (–1031T/C, –863C/A, –857T/C, –308A/G and +489A/G) with SLE in Taiwanese patients and controls. Our results indicate that 1) the frequency of the A-allele at –863 position was significantly higher in SLE patients (odds ratio = 1.46; 95% CI = 1.02–2.08); 2) the frequency of the A-allele at +489 position was significantly higher in SLE patients (odds ratio = 1.79; 95% CI = 1.21–2.65); 3) the AA or GA genotype frequencies at +489 position were significantly increased in SLE patients (AA genotype: odds ratio = 11.20; 95% CI = 1.36–92.55; GA genotype: odds ratio = 1.63; 95% CI = 1.03–2.58); 4) no significant association of TNF- haplotypic distributions was observed, except for the haplotypes TCCGA, CACGA and CCCGG; and 5) the genotype frequency of the polymorphisms at –1031 was significantly different in patients with antinuclear antibodies (P = 0.022). The allele and genotype frequencies of the polymorphisms at –863 were not significantly different. The genotype frequency of the polymorphisms at –857 was significantly different in patients with haematological disorder (P = 0.025). The frequency of A allele of the polymorphisms at –308 was significantly increased in patients with malar rash (P = 0.033), discoid rash (P = 0.023), photosensitivity (P = 0.037), oral ulcers (P = 0.002) and serositis (P = 0.029). The genotype frequency of the polymorphisms at +489 was significantly different in patients with discoid rash and photosensitivity (data not shown; discoid rash, P = 0.031; photosensitivity, P = 0.044). These results suggest that TNF- genetic polymorphisms contribute to SLE susceptibility in the Taiwanese population.

Longitudinal expression of type I interferon responsive genes in systemic lupus erythematosus

Thu, 17 Sep 2009 02:33:30 PDT

Cross-sectional studies of patients with systemic lupus erythematosus (SLE) have demonstrated an association between activation of type I interferon (IFN) pathway and disease activity. This study examined longitudinal changes in IFN-regulated gene expression in peripheral blood using microarrays. A cross-section of 66 patients from the Autoimmune Biomarkers Collaborative Network SLE archive was evaluated. We also examined paired samples from a 15 patient subset collected during a period of low disease activity (Baseline) and at a subsequent flare event, and baseline scores of 29 patients who maintained low disease activity. IFN response (IFNr) scores were calculated from three IFN-regulated genes. Overall, higher IFNr scores were associated with increased disease activity. However, IFNr scores were not significantly different between the paired Baseline and Flare samples. An extended longitudinal analysis in 11 patients indicated little change in IFNr scores over time, even during dynamic disease activity. In patients with low disease activity, IFNr scores were not different between patients who experienced a subsequent flare and those who maintained low disease activity. In summary, although higher IFNr scores were associated with greater disease activity, IFNr scores of individual patients did not correlate with changes in disease severity or flare risk.

Digital vasculitis in systemic lupus erythematosus: a minor manifestation of disease activity?

Thu, 17 Sep 2009 02:33:30 PDT

The objective of this study is to determine if digital vasculitis (DV), a clinical manifestation with a high systemic lupus erythematosus disease activity index (SLEDAI) score, is associated with lupus severity. DV and other clinical manifestations defined according to the SLEDAI were evaluated in 168 consecutive patients with systemic lupus erythematosus (SLE). Two groups were defined according to presence (DV+, n = 27) or absence of DV (DV–, n = 141) at the time of evaluation. The exclusion criterion was the presence of antiphospholipid syndrome (Sapporo’s criteria). The two groups were comparable with regard to age (P = 0.09), gender (P = 1.00), white race (P = 0.81), and disease duration (P = 0.78). Compared to the DV– group, the DV+ group had a significantly higher frequency of mucocutaneous manifestations (66.7 vs. 39.0%, P = 0.01), haematological abnormalities (22.2 vs. 6.4%, P = 0.02) and constitutional symptoms (11.1 vs. 0.7%, P = 0.01). Renal and neurological involvements were similar in both groups (P = 0.57 and P = 1.00, respectively). The evaluation of each SLEDAI parameter confirmed that the DV+ group had higher frequencies of mild manifestations, such as new rash (P = 0.02), alopecia (P = 0.02), oral ulcers (P = 0.045), fever (P = 0.01) and leucopenia (P = 0.005). In contrast, both groups had similarly increased anti-dsDNA (P = 0.78) and decreased complement levels (P = 0.29). In conclusion, DV in patients with SLE identifies a subgroup of a mild disease. The high ‘weighted’ index attributed to this alteration in the SLEDAI score should therefore be revised.

Renal cell apoptosis in human lupus nephritis: a histological study

Faurschou, M, Penkowa, M, Andersen, C., Starklint, H, Jacobsen, S — Thu, 17 Sep 2009 02:33:30 PDT

Nuclear autoantigens from apoptotic cells are believed to drive the immunological response in systemic lupus erythematosus (SLE). Conflicting data exist as to the possible renal origin of apoptotic cells in SLE patients with nephritis. We assessed the level of renal cell apoptosis in kidney biopsies from 35 patients with lupus nephritis by means of terminal deoxynucleotidyl-transferase (TdT)-mediated deoxyuridine triphosphate (dUTP)-digoxigenin nick end labeling (TUNEL). Five samples of normal kidney tissue served as control specimens. We did not observe apoptotic glomerular cells in any of the control or nephritis biopsies. Scarce apoptotic tubular cells were seen in 13 of 35 (37%) of the nephritis specimens and in two of five (40%) of the control sections. Within the SLE cohort, patients with TUNEL-positive tubular cells in their renal biopsies had significantly higher activity index scores for tubulointerstitial mononuclear cell infiltration than patients without apoptotic tubular cells in their biopsies (P = 0.01). Furthermore, the level of tubular cell apoptosis displayed a statistically significant, positive correlation with the activity index score for mononuclear cell infiltration (r_s = 0.472, P = 0.004) but not with scores for other activity or chronicity index components. These observations indicate that the degree of tubular cell apoptosis correlates with the severity of tubulointerstitial inflammation in SLE-associated nephritis. However, our findings do not suggest that apoptotic renal cells constitute a quantitatively important source of auto-antibody-inducing nuclear auto-antigens in human lupus nephritis.

The effects of previous hysterectomy on lupus

Thu, 17 Sep 2009 02:33:30 PDT

Hysterectomy is one of the most common surgical procedures performed in United States, and currently, one in three women in United States has had a hysterectomy by the age of 60 years. Systemic lupus erythematosus (SLE) is a common autoimmune disease and especially targets women of childbearing age at least 10 times higher than men, which reflects the major role of female sex hormones. In this retrospective study, we evaluate the potential effects of previous hysterectomy in our lupus cohort. Data collected from study subject questionnaires were obtained from the Lupus Family Registry and Repository (LFRR) at the Oklahoma Medical Research Foundation. Hysterectomy data were available from 3389 subjects. SLE patients with a positive history of hysterectomy have been selected and compared with matched lupus patients with a negative history of hysterectomy and healthy controls. Association analyses were performed, and the P values and adjusted odds ratios (ORs) were calculated. SLE patients with a negative history of hysterectomy more likely had kidney nephritis or positive anti-dsDNA than age-matched SLE patients with a history of hysterectomy before disease onset. This effect was independent of ethnicity with an OR of 6.66 (95% CI = 3.09–14.38, P = 1.00 x 10^–8) in European patients and 2.74 (95% CI = 1.43–5.25, P = 0.001) in African-Americans. SLE patients with a positive history of hysterectomy before disease onset also had a later age of disease onset (P = 0.0001) after adjustment for age and race. Our findings support the notion that the influence of female sex hormones in SLE and various clinical findings are tremendous and that surgical menopause such as this could significantly affect the outcome of disease and clinical manifestations.

Pulmonary hypertension in polymyositis-dermatomyositis: clinical and hemodynamic characteristics and response to vasoactive therapy

Minai, O. — Thu, 17 Sep 2009 02:33:30 PDT

The increased incidence of pulmonary hypertension and its association with decreased survival is well-recognised in patients with systemic sclerosis. This association is not widely appreciated in patients with polymyositis-dermatomyositis. We report clinical and hemodynamic characteristics and response to vasoactive therapy in three patients with polymyositis-dermatomyositis and pulmonary hypertension and discuss them in light of the available literature.

Isolated elevation of IgA anti-{beta}2glycoprotein I antibodies with manifestations of antiphospholipid syndrome: a case series of five patients

Kumar, S, Papalardo, E, Sunkureddi, P, Najam, S, Gonzalez, E., Pierangeli, S. — Thu, 17 Sep 2009 02:33:30 PDT

Current diagnostic classification criteria recommend elevated titres of anti-cardiolipin (aCL) and/or anti-β₂GPI antibody by ELISA IgG or IgM and/or lupus anticoagulant (LA) to confirm antiphospholipid syndrome (APS). Although IgA aPL antibodies have been shown to be pathogenic in animal models of APS, their clinical significance has remained elusive. We report four cases of exclusive IgA anti-β₂GPI antibody sero-positivity with concomitant clinical manifestations associated with APS. Four of the five patients were LA negative. 1) Thirty-eight-year-old African-American female with SLE presented with resolving digital ulcers. Serum IgA anti-β₂GPI antibody titres were 118.5 SAU (normal range: 0–20 SAU). 2) Twenty-seven-year-old African-American woman with SLE was evaluated for recent onset of severe headaches, unresponsive to analgesics and anti-migraine medications. MRI of the brain revealed hyper-intensities in the white matter in the frontal lobes. Serum IgA anti-β₂GPI antibody titres were 29.1 Standard A Units (SAU). 3) Thirty-two-year-old Hispanic female with history of two unexplained miscarriages and negative serologies for SLE. Serum IgA anti-β₂GPI antibody titres were 102.0 SAU. 4) Twenty-five-year-old white female with history of recent unexplained miscarriage in the 11th week of gestation and associated complaints of numbness and tingling in her hands. Her IgA anti-β₂GPI antibody titre was 62.0 SAU. 5) Twenty-five-year-old African-American woman with SLE, positive for anti-Ro antibodies with a history of ischemic fingers, a pregnancy loss and recent pregnancy complicated due to pre-eclampsia. Her LA was positive and her IgA anti-β₂GPI antibody titer was 186.0 SAU. This case series supports that elevated IgA anti-β₂GPI antibody titres may identify additional patients who have clinical features of APS but who do not meet current diagnostic criteria.

Gigantomastia and autoimmunity: a case report

Le, E., McGirt, L., Abuav, R — Thu, 17 Sep 2009 02:33:30 PDT

Gigantomastia is a rare breast condition characterised by diffuse, rapid, and excessive breast hypertrophy that can result in symptoms ranging from pain to necrosis and sepsis. It typically occurs in the setting of marked hormonal changes such as puberty and pregnancy. Rarely, gigantomastia has been reported to develop in the setting of an autoimmune illness. We present a case of gigantomastia developing in a patient with systemic lupus erythematosus, who was treated with methotrexate and bilateral mammoplasty.

Metabolic syndrome in Argentinean patients with systemic lupus erythematosus

Thu, 17 Sep 2009 02:33:30 PDT

The objective was to determine the prevalence of the metabolic syndrome (MS) in patients with systemic lupus erythematosus (SLE) in Argentina, to assess the factors associated to it, and to compare the results with a control group with non-inflammatory disorders. The study included 147 patients with SLE and 119 controls. MS was defined according to criteria by the American Heart Association/National Heart, Lung, and Blood Institute (AHA/NHLBI) Scientific Statement. Demographic characteristics, Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and Systemic Lupus International Collaborating Clinics/ACR Damage Index (SDI) were assessed as well as administration, maximum dose and cumulative dose of prednisone and hydroxychloroquine (HCQ). MS prevalence was 28.6% (CI 95%: 21.4–36.6) in patients with SLE and 16% in controls (P = 0.0019). Patients with SLE presented higher arterial hypertension frequency compared with controls (43 vs 25%, P = 0.007). When comparing lupus patients with MS (n = 41) and without MS (n = 106), no significant differences were observed regarding duration of the disease, SLEDAI or cumulative prednisone dose. Cumulative damage was associated independently with MS (OR 1.98; P = 0.021), whereas HCQ use was found to be protective (OR 0.13; P = 0.015). Patients with lupus presented higher MS prevalence than controls with non-inflammatory disorders, and occurrence of arterial hypertension was also higher. MS was associated with cumulative damage; the use of HCQ showed to be protective against presence of MS.

Supraspinatus tendon rupture in lupus: a rarity

Prabu, V., Agrawal, S, Kishore, J., Narsimulu, G — Thu, 17 Sep 2009 02:33:30 PDT

Microangiopathic haemolytic anaemias in systemic lupus erythematosus

Hunt, B. — Thu, 17 Sep 2009 02:33:30 PDT

The origin of mixed connective tissue disease: a stimulus for autoimmune disease research

Sharp, G. — Thu, 17 Sep 2009 02:47:32 PDT

Validation of the Spanish, Portuguese and French versions of the Lupus Damage Index questionnaire: data from North and South America, Spain and Portugal

Thu, 17 Sep 2009 02:47:32 PDT

We have previously developed and validated a self-administered questionnaire, modelled after the Systemic Lupus International Collaborating Clinics Damage Index (SDI), the Lupus Damage Index Questionnaire (LDIQ), which may allow the ascertainment of this construct in systemic lupus erythematosus (SLE) patients followed in the community and thus expand observations made about damage. We have now translated, back-translated and adapted the LDIQ to Spanish, Portuguese and French and applied it to patients followed at academic and non-academic centres in North and South America, Portugal and Spain while their physicians scored the SDI. A total of 887 patients (659 Spanish-speaking, 140 Portuguese-speaking and 80 French-speaking patients) and 40 physicians participated. Overall, patients scored all LDIQ versions higher than their physicians (total score and all domains). Infrequent manifestations had less optimal clinimetric properties but overall agreement was more than 95% for the majority of items. Higher correlations were observed among the Spanish-speaking patients than the Portuguese-speaking and French-speaking patients; further adjustments may be needed before the Portuguese and French versions of the LDIQ are applied in community-based studies. The relationship between the LDIQ and other outcome parameters is currently being investigated in a different patient sample.

Ultraviolet B exposure of peripheral blood mononuclear cells of patients with systemic lupus erythematosus inhibits DNA methylation

Wang, G., Zhang, M, Li, X., Zhang, H, Chen, W, Kan, M, Wang, Y. — Thu, 17 Sep 2009 02:47:32 PDT

Systemic lupus erythematosus (SLE) is an autoimmune inflammatory disease, in which sunlight (especially ultraviolet B (UVB) 290–320 nm) is known to induce exacerbation of disease. DNA methylation regulates gene expression, and hypomethylation is associated with abnormal cell function in SLE. The purpose of this study was to investigate the effect of UVB on DNA methylation in SLE and its significance in the pathogenesis of SLE. Forty-five patients with SLE and 20 healthy controls were enrolled in the study, which involved the investigation of DNA methylation and DNA methyltransferase 1 (DNMT1) of peripheral blood mononuclear cells with UVB irradiation. Our results demonstrate the following: The level of DNA methylation in patients with SLE was lower than that in the control group. DNA methylation was decreased after UVB irradiation at different dosages especially in patients with marlar rashes and leucopenia, but no significant difference was observed in the DNMT1 mRNA expression. DNA methylation levels in patients with active SLE were more sensitive to UVB. In conclusion, UVB exposure is able to inhibit DNA methylation, which subsequently takes part in the pathogenesis of SLE.

IAN5 polymorphisms are associated with systemic lupus erythematosus

Lim, M., Sheen, D., Kim, S., Won, S., Lee, S-S, Chae, S-C, Chung, H-T, Shim, S. — Thu, 17 Sep 2009 02:47:32 PDT

Systemic lupus erythematosus (SLE) is a representative autoimmune disease, which is frequently associated with lymphopenia. Biobreeding (BB) rat is a typical animal model which develops autoimmune diseases with lymphopenia which results from a frame-shift mutation in the immune-associated nucleotide (IAN) 5 gene. IAN5 is involved in the regulation of T-cell activation and survival. To examine the association of IAN5 gene with SLE, we scrutinised the single nucleotide polymorphisms (SNPs) in the IAN5 gene. We conducted a case–control study where 132 SLE patients, 505 rheumatoid arthritis (RA) patients, and 546 controls were genotyped for four SNPs in the IAN5 gene. Two SNPs (+2071C > T and +2677G > A) were associated with susceptibility to SLE (P = 0.040 and 0.045, respectively), and –4432G > A SNP was associated with the development of leukopenia (P = 0.028) and the requirement of steroid pulse therapy (P = 0.040) in SLE patients. Haplotype analyses showed that Ht1(CTCG) was associated with susceptibility to SLE (P = 0.036), and Ht4(ACCG), Ht5(ACTA) and Ht6(GCCG) were associated with the development of nephritis (P = 0.017, 0.019, 0.022, respectively). In conclusion, the IAN5 polymorphisms were associated with susceptibility to SLE and the development of clinical disease manifestations in a strictly Korean population.

Pulmonary involvement of systemic lupus erythematosus: analysis of 90 necropsies

Quadrelli, S., Alvarez, C, Arce, S., Paz, L, Sarano, J, Sobrino, E., Manni, J — Thu, 17 Sep 2009 02:47:32 PDT

Pleuropulmonary manifestations of systemic lupus erythematosus (SLE) have been reported to be of variable prevalence, depending on the diagnostic methods used. The objective of this study was to determine the anatomopathological prevalence and the nature of lung involvement associated with SLE and to define if there were differences in the grade and type of pulmonary involvement in patients who had died at different time periods, before or after 1996. Complete autopsy studies of 90 patients with SLE diagnosis carried out between 1958 and 2006 and their clinical records were studied. All patients fulfilled the American College of Rheumathology (ACR) diagnostic criteria for SLE. Two groups of patients were analyzed: patients who had died before 1996 and those deceased in 1996–2006. Some pleuropulmonary involvement was detected in 97.8% of the autopsies. The most frequent findings were pleuritis (77.8%), bacterial infections (57.8%), primary and secondary alveolar haemorrhages (25.6%), followed by distal airway alterations (21.1%), opportunistic infections (14.4%) and pulmonary thromboembolism (7.8%), both acute and chronic. No cases of acute or chronic lupus pneumonitis were found. Opportunistic lung infections were invasive aspergillosis, disseminated strongyloidiasis, mucormicosis and Pneumocystis carinii. Only three of 23 patients with alveolar haemorrhage showed capillaritis. The four patients with primary pulmonary hypertension (PHT) had plexiform lesions. Deceased patients’ age at death (46.09 ± 11.01 vs 30.3 ± 11.5 years, P < 0.0001) as well as survival time from diagnosis date (11.8 ± 11.2 vs 4.4 ± 4.9 years, P < 0.0001) in the second time period evaluated were significantly higher. However, there were no statistically significant differences in the prevalence of any of the pulmonary manifestations. Sepsis was considered the major cause of death without significant differences in both groups. Our results show that pulmonary manifestations directly caused by systemic lupus erythematosus are very uncommon and that their prevalence has not changed in the past 10 years. Pulmonary infection is still the most frequent affection, and it is an important cause of death in patients with lupus.

Treatment of femoral head osteonecrosis in patients with systemic lupus erythematosus by free vascularised fibular grafting

Sun, Y, Zhang, C., Chen, S., Sheng, J., Jin, D., Zeng, B. — Thu, 17 Sep 2009 02:47:32 PDT

The purpose of this study was to review the radiographs of symptomatic femoral head osteonecrosis in patients with systemic lupus erythematosus (SLE) and to assess the results of treatment using free vascularised fibular grafting. We retrospectively reviewed 50 patients (80 hips) with SLE who underwent free vascularised fibular grafting for osteonecrosis of the femoral head. All patients were followed up for at least 2 or more years (average, 4.3 years). The mean Harris hip score improved from 72 to 88. At the latest follow-up, we found improved or unchanged radiographs in 12 of initially Stage II hips and in 60 of 64 Stage III or IV hips. No hips failed treatment and underwent total hip arthroplasty. The data suggest that free vascularised fibular grafting was successful in maintaining joint function and in delaying the need for joint replacement procedure.

Expression profile of HIN200 in leukocytes and renal biopsy of SLE patients by real-time RT-PCR

Kimkong, I, Avihingsanon, Y, Hirankarn, N — Thu, 17 Sep 2009 02:47:32 PDT

HIN200 is a human IFN-inducible gene and homologous to murine IFI202 gene, which was identified as a candidate gene for SLE susceptibility in lupus mouse model. We determined these gene expressions in leukocytes from 20 SLE patients and 10 healthy controls and in renal biopsies from 29 SLE patients and 15 kidney donors using sensitive real-time reverse transcriptase–polymerase chain reaction (RT-PCR). The expressions of MNDA, IFIX, IFI16 and AIM2 genes significantly increased in leukocytes but not in kidney biopsies from SLE patients as compared to the control individuals, with P = 0.0003, P = 0.0056, P = 0.0002 and P < 0.0001, respectively. We also assessed the expression profiles of IFIX and IFI16 isoforms using semi-quantitative RT-PCR. We found up-regulation of B isoform (short product) of IFI16 in SLE patients. In addition, the expression levels were analyzed in correlation with disease activity and clinical characteristics. Interestingly, higher expression of MNDA was observed in patients who were positive for anti-dsDNA antibodies than in patients who were negative (P = 0.0276). In conclusion, it is suggested that the HIN200 genes have a role in SLE pathogenesis. Our study also observed a possible important role of a specific short isoform of IFI16 as well as a link between MNDA and anti-dsDNA antibody production.

Class IV-G and IV-S lupus nephritis in Chinese patients: a large cohort study from a single center

Yu, F, Tan, Y, Wu, L-H, Zhu, S-N, Liu, G, Zhao, M-H — Thu, 17 Sep 2009 02:47:32 PDT

This study is to assess the difference between IV-G and IV-S in a large cohort of Chinese patients with lupus nephritis. The detailed data of patients with subclass IV-G and IV-S were retrospectively analyzed. Serum ANCA and anti-C1q antibodies were detected. A total of 172 cases were classified as class IV, including 152 cases with IV-G and 20 cases with IV-S. In IV-S, the level of haemoglobin was significantly higher (P = 0.024), proteinuria was milder (P = 0.003), serum creatinine was lower (P = 0.021), serum C3 was higher (P = 0.045) and the ratio of positive serum anti-cardiolipin antibodies was higher (P = 0.014). On pathological evaluation, the ratio of glomerular fibrinoid necrosis was significantly higher (P = 0.006) and the score of endocapillary hypercellualrity, interstitial inflammation and total activity indices was significantly lower (P < 0.001, P = 0.01, P = 0.006, respectively) in IV-S. The frequency of serum ANCA was significantly higher in IV-S than that in IV-G (20 vs 4.6%, P = 0.008). The frequencies of anti-C1q IgG1 and IgG3 subclass were significantly higher in IV-G (P = 0.006, P = 0.011, respectively). There are significant differences in clinical and pathological manifestations between IV-S and IV-G lupus nephritis which need further investigation.

Extracorporeal shockwave for hip necrosis in systemic lupus erythematosus

Wang, C., Ko, J., Chan, Y., Lee, M., Chen, J., Wang, F., Yang, K., Huang, C. — Thu, 17 Sep 2009 02:47:32 PDT

Patients with systemic lupus erythematosus (SLE) frequently received corticosteroid therapy, resulting in osteonecrosis of the femoral head (ONFH). Prior studies demonstrated the effectiveness of extracorporeal shockwave treatment (ESWT) for ONFH.. This study evaluated the effectiveness of ESWT for ONFH in patients with SLE. We studied 39 patients, including 15 patients with SLE (26 hips) and 24 controls (29 hips). To each affected hip we applied ESWT (6000 impulses at 28 kV in a single session). Patients were ambulated with partial weight bearing for 4–6 weeks. The primary endpoint was the need for hip replacement. The secondary endpoints were improvement in hip pain and function and image changes on X-ray and MRI. Patients received total hip replacement in 12% of patients with SLE and in 14% of controls (P = 0.802). There was no statistically significant difference in pain scores (0.86 vs. 0.89; P = 0.467) and function scores (89% vs. 91%; P = 0.194) between patients with SLE and controls. SLE response to ESWT for ONFH is comparable with ONFH in patients without SLE.

Elevated levels of serum antibodies against Saccharomyces cerevisiae mannan in patients with systemic lupus erythematosus

Dai, H, Li, Z, Zhang, Y, Lv, P, Gao, X. — Thu, 17 Sep 2009 02:47:32 PDT

This study was undertaken to investigate whether levels of anti-Saccharomyces cerevisiae mannan antibodies (ASCMAs), a serological marker for Crohn’s disease, seronegative spondyloarthritis and Behcet’s disease, also correlate with systemic lupus erythematosus (SLE) in humans. Serum samples from healthy volunteers (n = 152) and patients with SLE (n = 40) were compared for ASCMA-IgA, -IgG and -IgM levels using enzyme linked immunosorbent assays. ASCMA-IgG, but not IgM and IgA, prevalence was significantly raised in active SLE patients (57.5%) compared with healthy controls (8.5%). ASCMA-IgG levels in SLE patients during remission were relatively lower, indicating a possible correlation with disease activity. These results differ from a previous study, which did not detect a difference between ASCMA levels in SLE patients and healthy control. It remains to be evaluated whether elevated ASCMA-levels are common to all rheumatic disorders.

Very long-term outcome of pure lupus membranous nephropathy treated with glucocorticoid and azathioprine

Mok, C., Ying, K., Yim, C., Ng, W., Wong, W. — Thu, 17 Sep 2009 02:47:32 PDT

The aim of this study is to report the long-term outcome of pure membranous lupus nephropathy (MLN) treated with glucocorticoid and azathioprine (AZA). A cohort of patients with SLE who had biopsy-confirmed pure MLN was treated initially with prednisone (0.8–1.0 mg/kg/day) and AZA (targeted to 2 mg/kg/day). Patients were followed for the following outcomes: remission rate at 12 months, renal flares, extra-renal flares and renal function deterioration. The cumulative risks of renal flares and renal function decline were studied by Kaplan–Meier analysis. Thirty-eight patients were studied (31 women; age 35.0 ± 9.2 years; mean SLE duration 48.5 ± 59 months; WHO Class Va 45%, Vb 55%). Twenty-two (58%) patients were nephrotic and four (11%) were hypertensive at presentation. All patients were treated with prednisolone (0.85 ± 0.24 mg/kg/day) and AZA (1.72 ± 0.43 mg/kg/day). At 12 months, 24 (67%) patients achieved complete response (CR), 8 (22%) had partial response (PR) and 4 (11%) were treatment resistant. After a follow-up of 12 ± 5.8 years, 19 episodes of renal flares (15 proteinuric and 4 nephritic) occurred in 13 (34%) patients. The cumulative risks of renal flares at 5, 10 and 15 years were 19.4, 32.0 and 36.8%, respectively. Retreatment with an augmented dosage of prednisolone, ± another immunosuppressive agent, resulted in CR and PR in 15 (79%) and 4 (21%) of these flare episodes, respectively. At last visit, three (8%) patients had doubling of serum creatinine, whereas six (16%) patients had decline of creatinine clearance by ≥30% (none developed end stage renal failure). Seven episodes of thromboembolic complications occurred in five (13%) patients and 11 episodes of infective complications (five major, six minor) were reported in seven (18%) patients. In the absence of co-existing proliferative lesions, MLN runs a relatively benign course with low risk of renal function deterioration. Treatment with high-dose prednisolone and AZA is effective, inexpensive and well-tolerated. Prolonged observation shows that one of three patients develop renal flares, which are often proteinuric and responsive to reinduction therapy.

Antithyroid antibodies in antiphospholipid syndrome: prevalence and clinical associations

Thu, 17 Sep 2009 02:47:32 PDT

Autoimmune thyroid disease has been associated with several systemic autoimmune disorders. However, limited data are available regarding the prevalence and clinical associations of thyroid autoimmunity in antiphospholipid syndrome (APS). Seventy-five patients with APS, 75 patients with systemic lupus erythematosus (SLE) and 75 healthy controls were tested for the presence of antithyroid antibodies (ATAs) (anti-thyroglobulin and anti-thyroid peroxidase [anti-TPO]) using commercial ELISA. Clinical data were also recorded. Although no significant differences in the prevalence of ATAs were detected among APS, SLE patient groups and healthy controls, a significant increase of anti-TPO antibodies in patients with APS-SLE was found. An increased prevalence of ATAs in APS population with ischemic central nervous system (CNS) clinical manifestations was also detected. We present novel associations between thyroid autoimmunity and ischemic CNS clinical manifestations in the setting of APS.

A rare opportunistic infection in a woman with systemic lupus erythematosus and multiple skin lesions

Hidron, A, Franco-Paredes, C, Drenkard, C — Thu, 17 Sep 2009 02:47:32 PDT

Cutaneous lesions in patients with systemic lupus erythematosus (SLE) represent diagnostic challenges. Opportunistic infections should be considered when lupus patients are on immunosuppressive therapy and other causes, such as disease activity, are less likely to explain the skin lesions. Within the spectrum of skin opportunistic infections that might occur in SLE patients, Blastomyces dermatitidis should be suspected when acid-fast positive material with no bacilliform organisms is seen on Ziehl-Nielsen skin biopsy preparations. In this study, we describe one patient with SLE on immunosuppressive therapy, who developed cutaneous blastomycosis despite living in a non-endemic area. Because of lack of awareness about this association and misinterpretation of the skin biopsy results, the diagnosis of atypical mycobacterial infection was initially considered. Subsequent proper tissue staining and interpretation revealed the correct diagnosis of disseminated cutaneous blastomycosis. This description represents the first report of this rare opportunistic skin infection in SLE, illustrating the importance of performing correct preparation and elucidation of the skin biopsy to avoid misdiagnosis and treatment delay.

Catastrophic antiphospholipid syndrome in a patient with Down syndrome

Medina, G., Calleja, C., Moran, M., Vera-Lastra, O., Jara, L. J — Thu, 17 Sep 2009 02:47:32 PDT

We report a patient with Down syndrome, under treatment with carbamazepine, levopromazine and clonazepam. After urinary infection he developed glans necrosis requiring excision of prepuce. Six hours post surgery he presented right-hand ischemia followed by arterial and venous thrombosis of the right thoracic extremity. Later, he progressed to a compartment syndrome and presented ischemia of toes. All the clinical manifestations developed over a week. Anticardiolipin (aCL) antibodies, lupus anticoagulant and perinuclear antineutrophil antibodies were positive. Anticoagulant and immunosuppressive treatment were initiated. Owing to the failure of both treatments, the patient underwent amputation of right hand and a toe. Histopathology revealed recent and old thrombosis of medium- and small-sized vessels without vasculitis. Diagnosis of catastrophic antiphospholipid syndrome (CAPS) was made. At present, the patient continues on oral anticoagulants, IgG aCL remains positive, and no further episodes of thromboses have been observed after 4 years of follow-up. To our knowledge, this is the first case of CAPS in a patient with Down syndrome.

Gelatinous transformation of the bone marrow in systemic lupus erythematosus

Yamamoto, M, Belmont, H., Utsunomiya, M, Hidaka, Y, Kishimoto, M — Thu, 17 Sep 2009 02:47:32 PDT

Gelatinous transformation of the bone marrow is a rare disease characterised by a focal marrow hypoplasia, fat atrophy and accumulation of extracellular mucopolysaccharides abundant in hyaluronic acid, which is often associated with extreme malnutrition and weight loss. There are only two reports describing its association with systemic lupus erythematosus (SLE). One described underlying diseases in 155 cases of gelatinous transformation of the bone marrow and found one case with clinical diagnosis of SLE, but no clinical details were provided. The other described three SLE patients with gelatinous transformation of the bone marrow; however, two of these were cachectic and one was diagnosed with concomitant tuberculosis. We describe one active SLE patient without other comorbidities whose pancytopaenia was histologically confirmed as gelatinous transformation. The combination of high-dose steroid, intravenous immunoglobulin and mycophenolate mofetil improved the peripheral blood cytopaenia and reversed the bone marrow abnormalities.

Prevalence, risk factors and outcome of digital gangrene in 2684 lupus patients

Liu, A, Zhang, W, Tian, X, Zhang, X, Zhang, F, Zeng, X — Thu, 17 Sep 2009 02:47:32 PDT

The aim of the study is to assess the clinical characteristics, risk factors and outcome of patients with systemic lupus erythematosus (SLE) complicated with digital gangrene. In all, 2684 consecutive SLE inpatients admitted to Peking Union Medical College Hospital from December 1997 to August 2007 were studied. Demographic data, clinical features, laboratory findings as well as therapeutic regimens were systematically reviewed and a database was established. Cases with digital gangrene were identified and followed up. 1) Eighteen patients with SLE were complicated with digital gangrene, the average age at event was 33.1 ± 11.8 years and the average disease duration was 99.1 ± 60.1 months. 2) Patients with SLE, with long disease duration (≥4 years), Raynaud’s phenomenon and elevated serum C-reactive protein (CRP) were more likely to develop digital gangrene, P = 0.006, 0.001, and 0.031, respectively, OR = 1.03 (95% CI 1.01, 1.04), 35.76 (95% CI 4.67, 273.83) and 9.93 (95% CI 1.23, 80.30), respectively. 3) Fifteen gangrene patients started prednisone ≥1 mg/kg/d, and 18 were treated with cyclophosphamide, although 8 cases failed and ultimately received digital amputation. Prompt corticosteroid treatment (prednisone ≥1 mg/kg/d started within 3 weeks) decreased the hazard of amputation, P = 0.073, HR = 0.13 (95% CI 0.01, 1.21). Long disease duration, Raynaud’s phenomenon and elevated serum CRP were independent predictive factors for SLE to develop digital gangrene. Early and aggressive corticosteroid treatment prevented gangrene from progression and improved prognosis.

Splenic volume in systemic lupus erythematosus

Thu, 17 Sep 2009 02:47:32 PDT

Idiopathic intracranial hypertension and systemic lupus erythematosus: a case report and review of the literature

Thu, 17 Sep 2009 02:47:32 PDT

Strong correlation in the serum levels of IgM rheumatoid factor and IgM anti-Chlamydia pneumoniae antibody

Iwamoto, M, Onishi, S, Minota, S — Thu, 17 Sep 2009 02:47:32 PDT