Interferon-λ3/4 genetic variants and interferon-λ3 serum levels are biomarkers of lupus nephritis and disease activity in Taiwanese

• Published in: Arthritis research & therapy Vol. 20; no. 1; pp. 193 - 11
• Main Authors: Chen, Ji-Yih, Wang, Chin-Man, Chen, Tai-Di, Jan Wu, Yeong-Jian, Lin, Jing-Chi, Lu, Ling Ying, Wu, Jianming
• Format: Journal Article
• Language: English
• Published: England BioMed Central 29.08.2018; BMC
• Subjects: Adult; Arthritis; Asian People - genetics; Biomarkers; Biomarkers - blood; Cytokines; Deoxyribonucleic acid; Disease; DNA; Female; Gene Frequency; Genetic Predisposition to Disease - ethnology; Genetic Predisposition to Disease - genetics; Genomes; Genotype; Haplotypes; Hepatitis; Humans; Interferon; Interferon λ; Interferons; Interleukins - blood; Interleukins - genetics; Lupus; Lupus Erythematosus, Systemic - blood; Lupus Erythematosus, Systemic - ethnology; Lupus Erythematosus, Systemic - genetics; Lupus nephritis; Lupus Nephritis - blood; Lupus Nephritis - ethnology; Lupus Nephritis - genetics; Male; Middle Aged; Pathogenesis; Polymorphism, Single Nucleotide; Rheumatology; Signal transduction; Systematic review; Systemic lupus erythematosus; Taiwan; Viral infections; Young Adult; Taiwan; Interferon λ; Systemic lupus erythematosus; Lupus nephritis
• ISSN: 1478-6362; 1478-6354; 1478-6362
• 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.