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Increased T-lymphocyte apoptosis in lupus correlates with disease activity and may be responsible for reduced T-cell frequency: a cross-sectional and longitudinal studyDepartment of Immunology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
Department of Immunology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
Department of Immunology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
Department of Immunology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
Department of Immunology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, Indiarnmisra{at}sgpgi.ac.in Apoptosis of lymphocytes is increased in patients with lupus. This may be pathogenic leading to increased load of autoantigens or may be a bystander effect of immune activation. A major unresolved issue is whether apoptosis is related to disease activity. Also its association with lymphocyte frequencies, anti-nucleosomal antibodies and serum IL 10 levels needs to be explored further. The aims of this study are to measure T- and B-lymphocyte apoptosis in patients with lupus and look at the effect of disease activity in a cross-sectional and longitudinal design and to determine frequency of T and B cells, level of anti-nucleosomal antibodies and serum IL 10 and assess their relationship with apoptosis. This study included 41 patients with SLE and 20 controls. A cutoff value of 4 in systemic lupus erythematosus disease activity index (SLEDAI) was used to separate active from inactive SLE. The frequency and degree of apoptosis of T and B lymphocyte were enumerated by flow cytometry using peripheral blood mononuclear cells (PBMCs) stained with CD3/CD19 and annexin V/PI. The data for T/B cell frequency are represented as % of these cells in the PBMC population, whereas percentage of apoptotic cells is out of total T or B cells. Serum anti-nucleosomal antibodies and IL 10 were assayed using ELISA. A repeat assessment of these parameters was carried out in 11 active patients when they became inactive. We found higher T-lymphocyte apoptosis in patients with SLE versus controls (14.8 ± 9.2, 7.2 ± 3.0; P < 0.05) and a lower frequency of T cells (72.7 ± 12.6, 79.9 ± 5.8; P < 0.05). T-lymphocyte apoptosis was higher in patients with active disease compared with inactive (18.5 ± 11.3, 11.6 ± 5.4; P = 0.05). Further, T-lymphocyte apoptosis directly correlated with SLEDAI (r = 0.37, P < 0.05) and inversely with T-cell frequency (r = –0.29, P < 0.05). Anti-nucleosomal antibodies correlated with SLEDAI but not apoptosis. On longitudinal follow-up, a decline in T-cell apoptosis was seen in patients with SLE, however this was not statistically significant. We confirmed a higher degree of apoptosis in T-lymphocytes in patients with SLE and found a direct correlation of T-cell apoptosis with disease activity. Patients had reduced T-cell frequency, which inversely correlated with T-cell apoptosis and may suggest a cause-effect relationship.
Key Words: anti-nucleosomal antibody • lymphocyte apoptosis • lymphocyte frequencies • pathogenesis of lupus • systemic lupus erythematosus
Lupus, Vol. 18, No. 9,
785-791 (2009) |
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