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Increased frequency of GM-CSF secreting PBMC in patients with active systemic lupus erythematosus can be reduced by immunoadsorption

Department of Medicine B, Westphalian Wilhelms-University, Muenster, Germany, willeke.peter{at}uni-muenster.de

B Schlüter

Institute of Clinical Chemistry and Laboratory Medicine, Westphalian Wilhelms-University, Muenster, Germany

H Schotte

Department of Medicine B, Westphalian Wilhelms-University, Muenster, Germany

M Erren

Institute of Clinical Chemistry and Laboratory Medicine, Westphalian Wilhelms-University, Muenster, Germany

E Mickholz

Department of Medicine B, Westphalian Wilhelms-University, Muenster, Germany

W Domschke

Department of Medicine B, Westphalian Wilhelms-University, Muenster, Germany

M Gaubitz

Department of Medicine B, Westphalian Wilhelms-University, Muenster, Germany

An objective was to determine the frequency of GM-CSF secreting peripheral blood mononuclear cells (PBMC) in patients with active systemic lupus erythematosus (SLE) and their relation to other cytokine secreting PBMC, activation markers on lymphocytes/monocytes, clinical manifestations and anti- dsDNA antibodies.A second objectivewas to further investigatethe influence of immunoadsorption(IA) therapy on these parameters.The number of GM-CSF, interleukin-1b (IL-1b), IL-6, interferon-g (INF-g) or tumour necrosis factor-a (TNF-a) secreting PBMC was assessed by ELISPOT assay in 10 patients with active SLE. Further, the expression of activation markers on lymphocytes and monocytes was determined by flow cytometry. Three courses of IA were performed in the patients. Seventeen healthy, age- and sex-matched volunteers served as controls. GM-CSF secreting PBMC were significantly increased whereas INF-g secreting cells were decreased in SLE patients. The expression of CD71 (transferrin receptor) on CD4 + T-cells and of the costimulatorymolecule CD86 on B-lymphocyteswas significantly increased in SLE patients. GM-CSF secreting PBMC and CD4 + /CD71 + T-cells correlated with anti-dsDNA antibody titres and decreased towards levels of controls during IA. Disease activity and anti-dsDNA autoantibody titres were significantly reduced after the treatment. Our results demonstrate significant alterations of cellular and humoral immunity in SLE patients. The impaired immunity can be modulated by IA. Thus IA may prove an immunomodulatory therapeutic option in addition to the mere depletion of anti-dsDNA autoantibodies.

Key Words: ELISPOT • GM-CSF • immunoadsorption • systemic lupus erythematosus

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