ABSTRACT
Introduction: Systemic lupus erythematosus [SLE] is an autoantigen driven T cell dependent autoimmune disease. Lupus nephritis is one of the most serious complications in SLE, occurring in up to 60% of the patients. SLE patients show increased apoptosis of peripheral blood mononuclear cells [PBMCs], especially T lymphocytes and decreased resistance of activated T cells to apoptosis. Fas, also known as APO-1 or CD95, is a cell surface protein that triggers apoptotic cell death with characteristic cytoplasmic and nuclear condensation and DNA fragmentation. The aim of this work was to evaluate Fas expression [as an apoptotic marker] on peripheral blood T lymphocytes in SLE patients in relation to disease activity and lupus nephritis
Subjects and methods: Thirty-five SLE patients and 15 normal controls were studied. Disease activity was assessed by SLAM score and patients were divided according to: a] disease activity [mildly active group with SLAM score <6, moderately active group from 6-12 and severely active group >12], b] the clinical presentation including the presence or absence of either lung, cardiac, neurological affection or nephritis as well as regard, c] WHO classes of lupus nephritis. Laboratory investigations included CBC, ESR, serum creatinine, urine examination, 24 hours urinary proteins, ANA and Anti-dsDNA, flowcytometric analysis of percentage of Fas expression [CD95+] on peripheral blood T lymphocytes [CD3+] and percutaneous renal biopsy in indicated patients with evidence of nephritis
Results: Percentage of CD3+CD95+ cells from SLE patients was statistically significantly increased compared to healthy controls [p<0.05]. Comparative study among the patients according to SLAM score was statistically significant [p<0.05] using ANOVA test with the highest percentage of apoptotic T lymphocytes in severely active group. When comparing each group with the control one, results showed statistically significant more apoptotic T cells in severely active SLE patients compared with controls. However, although the apoptotic T cells were increased in moderately active SLE patients, the data did not reach statistical significance in comparison with healthy controls nor with the mildly active group [p > 0.05]. Apart from nephritis [p<0.05], Fas expression was not associated with the clinical presentation of the patients, as regard the presence or absence of lung, cardiac or neurological affection [p>0.05]. The percentage of Fas expression was higher in class IIb than either class III or IV as well as patients without nephritis and those with nephritis without indication for renal biopsy [27.32+/-13.62 vs. 19.8, 19.14+/-5.12, 14.8+/-3.57 and 17.2+/-6.8]. However, on comparing only the patients who did renal biopsy, the renal parameters as well as the percentage of CD3+CD95+ cells was statistically non significant [P > 0.05]. Correlation between the percentage of CD3+CD95+ cells and different parameters revealed highly significant positive correlation as regard ESR, current steroid treatment dose and SLAM scoring, [p<0.001], statistically significant positive correlation as regard platelets, nephritis, arthritis, fever, lymphadenopathy and chronicity index in renal biopsy [p < 0.05], and tendency toward urinary albuminuria and casts. [p= 0.061 and 0.056 respectively]
In conclusion: The increased CD3+ CD95+ cells from patients with SLE and its correlation with disease activity suggests that abnormalities of apoptosis may be related to the pathogenesis of the disease [especially with high grades of activity] and its serious complication, nephritis. In patients with nephritis, the lower Fas expression [CD95+] on peripheral blood T lymphocytes [CD3+] in patients with class IV nephritis than those with class IIb nephritis could be possibly explained by the effect of treatment or by the natural process of the proliferative disease itself. However, further studies including large number of SLE patients, evaluating apoptosis both systemically and locally in tissue biopsies and studying various apoptotic pathways are needed to understand its role in the pathogenesis of the disease and its value as a therapeutic target