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

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.

Reduced expressions of Fas and Bcl-2 proteins in CD14+ monocytes and normal CD14 soluble levels in juvenile systemic lupus erythematosus

“…4,5 In previous studies from our group we have shown increased expressions of these molecules in both CD4þ and CD8þ T subtypes, and in B lymphocytes, suggesting an apoptosis-inducing imbalance. 4,5 On monocytes the reduced expressions of Fas and Bcl-2 proteins demonstrated herein may suggest an apoptosis-inhibiting imbalance of these cells, although previous studies have observed that monocytes from adult SLE patients present accelerated apoptosis and decreased survival.…”

“…4,5 In previous studies from our group we have shown increased expressions of these molecules in both CD4þ and CD8þ T subtypes, and in B lymphocytes, suggesting an apoptosis-inducing imbalance. 4,5 On monocytes the reduced expressions of Fas and Bcl-2 proteins demonstrated herein may suggest an apoptosis-inhibiting imbalance of these cells, although previous studies have observed that monocytes from adult SLE patients present accelerated apoptosis and decreased survival. 8,18,19 Considering that all previous studies related to functional monocyte apoptosis were performed in adult SLE patients, we speculate whether the accelerated apoptosis of phagocytic cells observed in these patients may be related to an altered expression of proapoptotic and antiapoptotic molecules.…”

Interaction between glutathione and apoptosis in systemic lupus erythematosus

“…The study from SLE patients showed an increase expression of Fas/Fas ligand and caspase-3 activity in T cells with a consequent increase in T lymphocyte apoptosis [50,108]. Further study showed up-regulation of apoptosis-related protein Bcl-2 and Fas in T and B lymphocytes of patients with juvenile-onset SLE [109]. It proposed that sFas may be a common feature in diseases involving Fas-mediated organ damage and that it might modulate both autoimmune response and FasL-mediated tissue damage in SLE.…”

The Role of Apoptosis Proteins and Complement Components in the Etiopathogenesis of Systemic Lupus Erythematosus

“…Falcini et al41 observed an increased expression of Bcl-2 protein in T lymphocytes. Additionally, Liphaus et al showed an increased expression of Fas protein in CD3+, CD4+, CD8+ and CD19+ cells in juvenile-onset SLE patients when compared to healthy controls and to patients with juvenile rheumatoid arthritis or juvenile dermatomyositis 42. Bcl-2 expression was also higher in T lymphocytes from juvenile-SLE patients, but not in B cells, when compared to healthy individuals 42.…”

“…Additionally, Liphaus et al showed an increased expression of Fas protein in CD3+, CD4+, CD8+ and CD19+ cells in juvenile-onset SLE patients when compared to healthy controls and to patients with juvenile rheumatoid arthritis or juvenile dermatomyositis 42. Bcl-2 expression was also higher in T lymphocytes from juvenile-SLE patients, but not in B cells, when compared to healthy individuals 42. In addition, there was a positive correlation between Fas and Bcl-2 expression in B cells and disease activity; different profiles of these proteins were demonstrated in patients with active and inactive disease 43…”