干扰素-λ3/4 基因变异和干扰素-λ3 血清水平是台湾狼疮肾炎和疾病活动的生物标志物。
Interferon-λ3/4 genetic variants and interferon-λ3 serum levels are biomarkers of lupus nephritis and disease activity in Taiwanese.
机构信息
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.
出版信息
Arthritis Res Ther. 2018 Aug 29;20(1):193. doi: 10.1186/s13075-018-1683-z.
BACKGROUND
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.
METHODS
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.
RESULTS
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.
CONCLUSIONS
IFN-λ3/4 genetic variants play a unique role in the development of lupus nephritis and SLE.
背景
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。
方法
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。
结果
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。
结论
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。
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