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Lupus nephritis (LN) is a common complication of systemic lupus erythematosus (SLE) diagnosed via histopathology of renal biopsy. Investigating surrogate markers to predict renal involvement in LN is a safe non-invasive method to be studied. One of those markers is Interleukin 35 (IL-35) which has an immunosuppressive and anti-inflammatory role in many autoimmune diseases. However, its role in LN still needs to be elucidated. This study aimed to evaluate serum levels of IL-35 in SLE patients with and without LN as a biomarker of renal involvement.
A cross-sectional comparative study in which we included 60 SLE patients fulfilling the new European Alliance of Associations for Rheumatology/American College of Rheumatology EULAR /ACR classification criteria of SLE, 30 with of them with LN [with any of the following: proteinuria (≥ 0.5 g/24 h or protein/creatinine ratio (PCR)≥300 mg/g), cellular casts, microscopic haematuria or evidence of LN in renal biopsy] and the rest (30 patients) without LN. Thirty matched healthy controls were included as well. We excluded patients with: SLE with end stage renal disease, other rheumatic or autoimmune diseases, renal diseases other than LN, diabetes, treatment with a monoclonal antibody or biologic agents, and Pregnant women. IL-35 level was measured using enzyme-linked immunosorbent assay (ELISA). SLE disease activity was assessed for patients by the systemic Lupus erythematosus Disease activity index 2000 (SLEDAI).
IL-35 level was not significantly higher in LN group compared with non-LN group (43.33% sensitivity and 53.33% specificity for prediction of LN in SLE patients). However, it was higher in SLE patients than controls. Regarding lupus activity, no significant association between IL-35 and SLEDAI score in LN and non-LN groups was found. In LN group, a negative correlation was observed between IL-35 and urine RBCs (r = - 0.491). Class 3(A) & class 4(A/C) LN had significantly higher IL-35 than other classes. Proliferative LN had higher (but non statistically significant) IL-35 compared to those with non-proliferative LN. Patients with antiphospholipid syndrome (APS) had significantly higher IL-35 compared to those without APS. Patients with positive Anti-ds-DNA also had higher IL-35 compared to those with negative Anti-ds-DNA.
Conclusions
Although there is a difference in serum IL-35 levels between SLE patients with and without LN, it is a poor predictor of renal involvement in SLE. higher levels of the IL-35 were associated with specific histopathological patterns of lupus nephritis.