Regional variations in serum IL-35 levels and association with systemic lupus erythematosus: a systematic review and meta-analysis

Interleukin (IL)-35 is an anti-inflammatory cytokine that regulates autoimmune diseases, including systemic lupus erythematosus (SLE). However, the association between the cytokine and disease may vary by geographical region. This study performed a meta-analysis to quantitatively assess the correlation between the serum IL-35 levels in SLE patients and sub-group analyses were conducted. Four main electronic databases—Scopus, Embase, Science Direct, PubMed—were searched for relevant studies. After a database search, Endnote software was used to find and remove duplicate studies. Random-effects models were used to estimate standard mean differences in serum/plasma IL-35 levels by Hedges’ g with 95% confidence intervals (CIs). Publication bias was assessed with funnel plots, and risk of bias was assessed according to the Newcastle-Ottawa Scale (NOS). Sixteen studies met the eligibility criteria and were included in a qualitative review; data from 15 studies were included in the meta-analysis. Total IL-35 levels (pg/mL) did not differ among patients with active SLE and healthy controls (Hedges’s g: 0.22, 95% CI − 0.51, 0.95, p = 0.55). Sub-group analysis revealed that IL-35 levels in patients with active SLE were lower than in healthy controls in Chinese studies (Hedges’s g: − 3.11, 95% CI − 5.72, − 0.51), but not in non-Chinese studies (Hedges’s g: 1.63, 95% CI − 0.31, 3.57). This regional difference was statistically significant (p < 0.01). The analysis comparing patients with inactive SLE and healthy controls showed a similar trend. This study suggests that serum IL-35 levels are lower in patients with SLE in studies from China, but not other regions. However, standardized protocols with large sample sizes are needed to confirm these findings.