Department of Medicine, Division of Allergy, Immunology and Rheumatology, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, No. 5, Fu-Shin St. Kwei-Shan, Tao-Yuan, Taiwan.
Department of Rehabilitation, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, No. 5, Fu-Shin St. Kwei-Shan, Tao-Yuan, Taiwan.
Arthritis Res Ther. 2018 Aug 29;20(1):193. doi: 10.1186/s13075-018-1683-z.
Type III interferons (IFNs) or IFN-λs are the newly discovered cytokines that primarily target the cells of epithelial and myeloid lineages, which are major components of kidneys. The current study aimed to investigate whether IFN-λs are involved in the pathogenesis of systemic lupus erythematosus (SLE) and lupus nephritis.
TaqMan allele discrimination assays were used to determine IFNL3/4 SNP genotypes of 1620 healthy controls and 1013 SLE patients (two independent cohorts consisting of 831 and 182 subjects, respectively) from Taiwan. The distributions of IFNL3/4 SNP genotypes and allele frequencies were compared between SLE patients and healthy controls and among SLE patients stratified by clinical phenotypes. ELISA was used to determine the serum IFN-λ3 concentrations of SLE patients.
All major IFN3/4 SNP alleles were significantly associated with the risk for lupus nephritis (rs8099917T, P = 0.0021, OR 1.75, 95% CI 1.24-2.47; rs12979860C, P = 0.0034, OR 1.65, 95% CI 1.18-2.30; rs4803217C, P = 0.0021, OR 1.76, 95% CI 1.25-2.48; and ss469415590TT, P = 0.0021, OR 1.73, 95% CI 1.23-2.42) among SLE patients. Similarly, the major IFNL3/4 SNP haplotype rs8099917T-ss469415590TT-rs12979860C-rs4803217C (or T-TT-C-C) was a significant risk factor for lupus nephritis (P = 0.0015, OR 1.68, 95% CI 1.22-2.32). Additionally, all minor IFN3/4 SNP alleles were significantly associated with SLE susceptibility in nephritis-negative SLE patients as compared to normal healthy controls (rs8099917G, P = 0.00177, OR 1.68, 95% CI 1.24-2.28; rs12979860T, P = 0.00299, OR 1.58, 95% CI 1.18-2.32; rs4803217A, P = 0.00176, OR 1.65, 95% CI 1.22-2.23; and ss469415590ΔG, P = 0.00176, OR 1.70, 95% CI 1.26-2.29). Furthermore, the elevated serum levels of IFN-λ3 were significantly correlated with the complement depression and the high SLE disease activities in SLE patients.
IFN-λ3/4 genetic variants play a unique role in the development of lupus nephritis and SLE.
III 型干扰素（IFN）或 IFN-λ 是新发现的细胞因子，主要针对上皮和髓系细胞，这是肾脏的主要成分。本研究旨在探讨 IFN-λ 是否参与系统性红斑狼疮（SLE）和狼疮性肾炎的发病机制。
采用 TaqMan 等位基因区分法检测来自台湾的 1620 名健康对照者和 1013 名 SLE 患者（两个独立队列，分别包含 831 名和 182 名受试者）的 IFNL3/4 SNP 基因型。比较 SLE 患者与健康对照者以及按临床表型分层的 SLE 患者的 IFNL3/4 SNP 基因型和等位基因频率分布。采用 ELISA 法测定 SLE 患者血清 IFN-λ3 浓度。
所有主要 IFN3/4 SNP 等位基因均与狼疮肾炎的发病风险显著相关（rs8099917T，P=0.0021，OR 1.75，95%CI 1.24-2.47；rs12979860C，P=0.0034，OR 1.65，95%CI 1.18-2.30；rs4803217C，P=0.0021，OR 1.76，95%CI 1.25-2.48；和 ss469415590TT，P=0.0021，OR 1.73，95%CI 1.23-2.42）。同样，IFNL3/4 SNP 主要单倍型 rs8099917T-ss469415590TT-rs12979860C-rs4803217C（或 T-TT-C-C）也是狼疮肾炎的显著危险因素（P=0.0015，OR 1.68，95%CI 1.22-2.32）。此外，与正常健康对照者相比，所有次要 IFN3/4 SNP 等位基因均与肾炎阴性 SLE 患者的 SLE 易感性显著相关（rs8099917G，P=0.00177，OR 1.68，95%CI 1.24-2.28；rs12979860T，P=0.00299，OR 1.58，95%CI 1.18-2.32；rs4803217A，P=0.00176，OR 1.65，95%CI 1.22-2.23；和 ss469415590ΔG，P=0.00176，OR 1.70，95%CI 1.26-2.29）。此外，IFN-λ3 血清水平升高与 SLE 患者的补体抑制和高 SLE 疾病活动度显著相关。
IFN-λ3/4 遗传变异在狼疮肾炎和 SLE 的发生发展中发挥独特作用。
