Interleukin-35 as a New Biomarker of Renal Involvement in Lupus Nephritis Patients

Abstract

Systemic lupus erythematosus (SLE) is an autoimmune connective tissue disease with a wide range of clinical presentations. Lupus nephritis (LN) is the most serious manifestation of SLE. , a member of the interleukin-12 family, has been identified as a novel anti-inflammatory cytokine. In the past ten years, the role of IL-35 in inflammatory and autoimmune diseases has been studied extensively. Serum IL-35 levels, however, have not been studied in LN patients. The aim of the study was to determine serum IL-35 levels in SLE patients with and without nephritis, and their clinical values. The study was carried out on 120 SLE patients, which comprised 80 LN patients and 40 SLE patients without nephritis. SLE disease activity was measured according to Systemic Lupus Erythematosus Dis ease Activity Index-2 k (SLEDAI-2 k). Statistical evaluation was based on Mann-Whitney U-test, t-test, chi-square test, Spearman rank correlation test and Pearson's correlation test. The result showed that active SLE patients (n = 65) have lower serum IL-35 levels, compared to inactive SLE patients (n = 55, P < 0.001). Furthermore, serum IL-35 levels were significantly lower in LN patients (n = 80) than SLE patients without nephritis (n = 40, P = 0.013). Serum IL-35 levels had significant correlations with SLEDAI-2k (r = -0.626, P < 0.001) in SLE patients and estimated glomerular filtration rate (eGFR) (r = 0.348, P = 0.002) in LN patients. These results indicate that IL-35 is a potential biomarker of renal involvement in LN patients.

Association between Interleukin 35 Gene Single Nucleotide Polymorphisms and Systemic Lupus Erythematosus in a Chinese Han Population

“…In the present study, the prevalence of renal disorder in SLE patients was 37.6% with median disease duration of 4.06 years. Previous study has suggested that serum IL-35 could be served as a potential biomarker of renal involvement in SLE patients; the serum levels of IL-35 were significantly lower in nephritis patients with higher levels of serum creatinine, blood urea nitrogen and blood uric acid [51]. Our result adds novel evidence in elucidating the genetic underpinnings driving nephritis among SLE patients.…”

IL‐35 ameliorates collagen‐induced arthritis by promoting TNF‐α‐induced apoptosis of synovial fibroblasts and stimulating M2 macrophages polarization

“…Interleukin‐35 (IL‐35), as a new member of the IL‐12 family , plays a key role in certain autoimmune diseases, including diabetes , antiphospholipid syndrome , systemic lupus erythematosus , and immune thrombocytopenia . IL‐35‐producing B cells were identified as pivotal players in the negative regulation of immunity as well, including the inhibition of macrophages and inflammatory T cells .…”

Research Progress on Regulatory B Cells in Systemic Lupus Erythematosus

“…However, IL-35 [32] and TGF- β [31, 33] also play key roles in the pathogenesis of SLE. Study [34] found serum IL-35 levels were lower in active SLE compared to inactive disease and inversely correlated with SLEDAI-2K [34]. Furthermore, serum IL-35 levels were lower in patients with LN compared to SLE patients without LN [34].…”

“…Study [34] found serum IL-35 levels were lower in active SLE compared to inactive disease and inversely correlated with SLEDAI-2K [34]. Furthermore, serum IL-35 levels were lower in patients with LN compared to SLE patients without LN [34]. Serum IL-35 levels were found decreased in patients with SLE [35] and negatively correlated with the disease activity index.…”