Association between IL-37 and Systemic Lupus Erythematosus Risk

Abstract

Interleukin-37 (IL-37) is an anti-inflammatory cytokine. In our former study, we found increased plasma IL-37 levels in systemic lupus erythematosus (SLE) patients. However, relationship between IL-37 levels and clinical laboratory characteristics of SLE patients has not been elucidated. In addition, association of <i>IL37</i> gene polymorphism with SLE risk needs to be discussed. A group of 580 individuals (220 SLE patients and 360 healthy controls) in a Southern Chinese Han population were recruited. Plasma IL-37 levels were evaluated using enzyme-linked immunosorbent assay (ELISA). Four single-nucleotide polymorphisms (rs3811047, rs2723186, rs2723176 and rs4364030) of <i>IL37</i> gene were genotyped. Relationship of IL-37 expression, <i>IL37</i> gene polymorphisms and clinical characteristics was discussed. We found that plasma levels of IL-37 were negatively associated with SLE disease activity index (SLEDAI) (r_s = -0.352, <i>P</i> = .001), and were higher in less active patients compared with active patients (<i>P</i> = .003). Decreased levels of IL-37 were found in SLE patients with discoid rash when compared to patients who did not have this symptom (<i>P</i> < .001). Plasma IL-37 levels were significantly lower in patients with hypocomplementemia comparing to those without this feature (<i>P</i> = .009). Levels of IL-37 in SLE with positive proteinuria were lower than patients with negative proteinuria (<i>P</i> = .046). Furthermore, allele distribution of rs2723186, rs4364030 between SLE cases and healthy individuals was significantly different (<i>P</i> = .001, <i>P</i> = .010, respectively). Genotype of rs4364030 was different between SLE cases and controls (<i>P</i> = .015). Haplotype analysis revealed that the frequency of haplotype CG (rs2723176 (C) +rs2723186 (G)) was higher in SLE, as compared with healthy individuals (<i>P</i> = .002). In conclusion, the plasma levels of IL-37 were related to SLE severity, and <i>IL37</i> gene polymorphisms (rs2723186, rs2723176 and rs4364030) may associate with SLE susceptibility.