Background Apoptotic defects have been proposed to explain the pathogenesis of systemic lupus erythematosus (SLE). Fas/APO-1 and FasL, members of the tumor necrosis factor (TNF) families, are involved in apoptosis. They are expressed in membrane-associated as well as soluble forms (sFas/APO-1 and sFasL).
Objectives The aim of this study is to determine serum levels of sFas/APO-1 and sFasL in patients with SLE.
Methods The study included 48 pts (90% females, age 30,0 [27,0–44,5] years (median [interquartile range 25%>75%]) with SLE (ACR criteria, 1997) and 10 controls (100% females without any rheumatic and infectious diseases, age 39,5 [31,0–45,0] years, p>0,05). SLE-related factors, including disease duration, clinical features, SLE Disease Activity Index (SLEDAI 2K) and Systemic Lupus International Collaborating Clinics (SLICC) damage index were evaluated in parallel with relevant laboratory findings (blood and urine tests, CRP, immunoglobulins G, A and M, complement C3 and C4 fragments and others), autoantibodies (ANA, antiDNA, ENA-SSA, -SSB, -Sm, -RNP-70, aPL). Serum levels of sFas/APO-1 (pg/ml) and sFasL (ng/ml) were measured by ELISA (Bender MedSystem GmbH, Austria). Statistical analyses were performed with STATISTICA program, version 8.0.
Results Mean SLE duration was 5,0 [1,0–12,0] years, SLEDAI 2K score - 9 [4–15], SLICC damage index score - 0 [0–1]. SLE pts had lower levels of sFas/APO-1 vs control (669,65 [487,90–791,40] vs 1456,90 [426,50–2060,80] pg/ml, p<0,01) and higher levels of sFasL vs control (0,10 [0,01–0,03] vs 0,07 [0,05–0,10] ng/ml, p<0,05). In SLE pts serum sFas/APO-1 level correlated with platelets absolute count (r=-0,292, p<0,05), creatinine (r=0,538, p<0,0001), urea (r=0,431, p<0,01), uric acid (r=0,698, p<0,000000), proteinuria (r=0,311, p<0,05), cylindruria levels (r=0,365, p<0,05), glomerular filtration rate (r=-0,341, p<0,05) and systolic blood pressure (r=0,327, p<0,05), SLEDAI 2K (r=0,342, p<0,05), antiSSA (r=-0,467, p<0,001), antiSSB (r=-0,338, p<0,05), ACL IgG (r=0,434, p<0,01), CRP concentrations (r=0,446, p<0,01) and ESR (r=0,428, p<0,01). We divided SLE pts into two groups: Group 1 included pts with lupus nephritis (n=24 (50%)), Group 2 – SLE pts without nephritis (n=24 (50%)). Pts from Group 1 had higher, but not statistically significantly, levels of sFas/APO-1 as compared to Group 2 levels (706,15 [601,35–974,05] vs 591,90 [464,25–754,85] pg/ml, p>0,05).
Conclusions The increased level of sFasL (a marker of apoptosis) and reduced level of sFas/APO-1 (apoptosis inhibitor that blocks binding of sFas/APO-1 to sFasL) in the study group is indicative of up-regulated apoptosis in SLE patients. Established correlation of sFas/APO-1 concentration with indicators of kidney damage and SLEDAI 2K score allows us to consider sFas/APO-1 as a marker of lupus nephritis and high SLE activity.
Disclosure of Interest None declared