TY - JOUR
T1 - Interferon-λ3/4 genetic variants and interferon-λ3 serum levels are biomarkers of lupus nephritis and disease activity in Taiwanese
AU - Chen, Ji Yih
AU - Wang, Chin Man
AU - Chen, Tai Di
AU - Jan Wu, Yeong Jian
AU - Lin, Jing Chi
AU - Lu, Ling Ying
AU - Wu, Jianming
N1 - Publisher Copyright:
© 2018 The Author(s).
PY - 2018/8/29
Y1 - 2018/8/29
N2 - 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 FDR = 0.0021, OR 1.75, 95% CI 1.24-2.47; rs12979860C, P FDR = 0.0034, OR 1.65, 95% CI 1.18-2.30; rs4803217C, P FDR = 0.0021, OR 1.76, 95% CI 1.25-2.48; and ss469415590TT, P FDR = 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 FDR = 0.00177, OR 1.68, 95% CI 1.24-2.28; rs12979860T, P FDR = 0.00299, OR 1.58, 95% CI 1.18-2.32; rs4803217A, P FDR = 0.00176, OR 1.65, 95% CI 1.22-2.23; and ss469415590ΔG, P FDR = 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.
AB - 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 FDR = 0.0021, OR 1.75, 95% CI 1.24-2.47; rs12979860C, P FDR = 0.0034, OR 1.65, 95% CI 1.18-2.30; rs4803217C, P FDR = 0.0021, OR 1.76, 95% CI 1.25-2.48; and ss469415590TT, P FDR = 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 FDR = 0.00177, OR 1.68, 95% CI 1.24-2.28; rs12979860T, P FDR = 0.00299, OR 1.58, 95% CI 1.18-2.32; rs4803217A, P FDR = 0.00176, OR 1.65, 95% CI 1.22-2.23; and ss469415590ΔG, P FDR = 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.
KW - Interferon λ
KW - Lupus nephritis
KW - Systemic lupus erythematosus
UR - http://www.scopus.com/inward/record.url?scp=85052600332&partnerID=8YFLogxK
U2 - 10.1186/s13075-018-1683-z
DO - 10.1186/s13075-018-1683-z
M3 - 文章
C2 - 30157968
AN - SCOPUS:85052600332
SN - 1478-6354
VL - 20
JO - Arthritis Research and Therapy
JF - Arthritis Research and Therapy
IS - 1
M1 - 193
ER -