Associations between blood IL-33 levels and IL-33 gene polymorphisms with susceptibility to systemic lupus erythematosus: A meta-analysis

Objectives This study investigated the relationship between circulating interleukin-33 (IL-33) levels and systemic lupus erythematosus (SLE) along with polymorphisms in the IL-33 gene and SLE susceptibility. Method The MEDLINE, EMBASE, and Cochrane Library databases (to May 2023) were searched for relevant publications. Using a meta-analysis we investigated serum/plasma IL-33 levels in patients with SLE and controls, and the relationship between IL-33 rs1929992, rs1891385, rs7044343, rs1095498, and rs10975579 polymorphisms and the risk of developing SLE. Results Nine studies focusing on 1,935 patients with SLE were included. IL-33 levels were significantly higher in the SLE group than in the control group (SMD = 2.140, 95% CI = 1.068–3.212, p < .001). Asian, European, and Arab groups have shown increased IL-33 levels in SLE populations, according to ethnic stratification. Regardless of the sample size, variable adjustment, data format, or publication year, the subgroup analysis showed significantly higher IL-33 levels in the SLE group. This meta-analysis supported the significance of the link between SLE and the IL-33 rs1891385 C allele (OR, 1.525; 95% CI, 11.310–1.777; p = .010). A similar association was found between the IL-33 rs1891385 C/A polymorphism and SLE, using homozygote comparisons and dominant and recessive models. However, this meta-analysis found no association between the IL-33 polymorphisms rs1929992, rs7044343, rs1095498, and rs10975579 and susceptibility to SLE. Conclusions This meta-analysis identified significantly higher levels of circulating IL-33 in patients with SLE as well as an association between IL-33 rs1891385 and SLE.