Copy number variations of interleukin-17F, interleukin-21, and interleukin-22 are associated with systemic lupus erythematosus.

Objective Systemic lupus erythematosus (SLE) represents the classic prototype of systemic autoimmune disease. The identification of the Th17 cell subset has provided new understanding regarding the underlying mechanisms of autoimmunity. Copy number variations (CNVS) have been discovered to have phenotypic consequences and are associated with various types of diseases. We undertook this study to explore a possible association between CNVS of Th17 cell–related genes and the risk of SLE. Methods We extracted genomic DNA and RNA from 938 SLE patients and 1,017 healthy controls. We examined CNVS of Th17 cell–related genes, including retinoic acid receptor–related orphan nuclear receptor γt, STAT-3, interleukin-6 (IL-6), transforming growth factor β, tumor necrosis factor α, IL-17A, IL-17F, IL-21, IL-22, IL-23A, CCL20, and CCR6, and levels of messenger RNA (mRNA) for IL-17F, IL-21, and IL-22. Results Genotype and allele frequencies for copy number amplifications of IL-17F, IL-21, and IL-22 were found to be significantly higher in SLE patients than in healthy controls. CNVS of IL-17F, IL-21, and IL-22 had no synergistic contribution to SLE. The mRNA expression of IL-17F, IL-21, and IL-22 in the samples with >2 copies of DNA was significantly higher than that in those with 2 copies of DNA. Conclusion Our findings indicate that CNVS of IL-17F, IL-21, and IL-22 are associated with the risk of SLE.