Increased Fas and Bcl-2 Expression on Peripheral Blood T and B Lymphocytes from Juvenile-Onset Systemic Lupus Erythematosus, but not from Juvenile Rheumatoid Arthritis and Juvenile Dermatomyositis

Bernadete L Liphaus,Solange Carrasco,Maria H B Kiss,Claudia Goldenstein-Schainberg

doi:10.1080/17402520600877786

Abstract

Defective regulation of apoptosis may play a role in the development of autoimmune diseases. Fas and Bcl-2 proteins are involved in the control of apoptosis. The aims of this study were to determine the expression of Fas antigen and Bcl-2 protein on peripheral blood T and B lymphocytes from patients with juvenile-onset systemic lupus erythematosus (JSLE), juvenile rheumatoid arthritis (JRA) and juvenile dermatomyositis (JDM). Thirty-eight patients with JSLE, 19 patients with JRA, 10 patients with JDM and 25 healthy controls entered the study. Freshly isolated peripheral blood mononuclear cells (PBMC) were stained for lymphocyte markers CD3, CD4, CD8, CD19 and for Fas and Bcl-2 molecules. Expressions were measured by three-color flow cytometry. Statistical analysis was performed using Kruskal–Wallis test. Percentages of freshly isolated T lymphocytes positively stained for Fas protein from JSLE patients were significantly increased compared to healthy controls, patients with JRA and patients with JDM. Percentages of B lymphocytes positive for Fas from JSLE patients were higher than healthy controls and JRA patients. In addition, Fas expression on T cells from patients with JRA was increased compared to JDM patients. Otherwise, Fas expression on T and B cells from JRA and JDM patients were similar to healthy controls. MFI of Bcl-2 positive T lymphocytes from JSLE patients were significantly increased compared to healthy controls and JRA patients. MFI of Bcl-2 protein on B lymphocytes from JSLE patients was similar to healthy controls and patients with JRA and JDM. Bcl-2 expression did not differ between JRA and JDM patients and healthy controls. In conclusion, increased expression of Fas and Bcl-2 proteins observed in circulating T and B lymphocytes from patients with JSLE, but not from patients with JRA and JDM, suggests that abnormalities of apoptosis may be related to the pathogenesis of JSLE and probably are not a result of chronic inflammation.

Highlights

IntroductionJuvenile systemic lupus erythematosus (JSLE), juvenile rheumatoid arthritis (JRA) and juvenile dermatomyositis (JDM) are autoimmune diseases with high morbidity and mortality in childhood (Behrens et al 1997; Andrade et al 2000; Szodoray et al 2003)
Fas expression on lymphocytes from Juvenile systemic lupus erythematosus (JSLE) patients were increased compared to juvenile rheumatoid arthritis (JRA) patients on CD3 þ, CD8 þ T cells and on CD19 þ B and compared to juvenile dermatomyositis (JDM) patients on CD3 þ, CD4 þ and CD8 þ T cells (Table I)
mean fluorescence intensity (MFI) of Bcl-2 was increased on lymphocytes from JSLE patients compared to JRA patients on CD3 þ, CD4 þ and CD8 þ T cells, but there was no difference compared to JDM patients (Table II)

Summary

Introduction

Juvenile systemic lupus erythematosus (JSLE), juvenile rheumatoid arthritis (JRA) and juvenile dermatomyositis (JDM) are autoimmune diseases with high morbidity and mortality in childhood (Behrens et al 1997; Andrade et al 2000; Szodoray et al 2003) These autoimmune diseases present dysfunction of T and B cells causing tissue infiltration of mononuclear cells and macrophages, tissue damage and production of autoantibodies (Behrens et al 1997; Andrade et al 2000; Szodoray et al 2003). These autoantigens can be presented to auto-reactive lymphocytes and drive to an autoimmune disease (Casciola-Rosen et al 1994; Emlen et al 1994; Wyllie 1997; Andrade et al 2000; Smolewska et al 2003).

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