Interferon-λ3/4 genetic variants and interferon-λ3 serum levels are biomarkers of lupus nephritis and disease activity in Taiwanese.
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, PFDR = 0.0021, OR 1.75, 95% CI 1.24-2.47; rs12979860C, PFDR = 0.0034, OR 1.65, 95% CI 1.18-2.30; rs4803217C, PFDR = 0.0021, OR 1.76, 95% CI 1.25-2.48; and ss469415590TT, PFDR = 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, PFDR = 0.00177, OR 1.68, 95% CI 1.24-2.28; rs12979860T, PFDR = 0.00299, OR 1.58, 95% CI 1.18-2.32; rs4803217A, PFDR = 0.00176, OR 1.65, 95% CI 1.22-2.23; and ss469415590ΔG, PFDR = 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.
['Chen|Ji-Yih|JY|', 'Wang|Chin-Man|CM|', 'Chen|Tai-Di|TD|', 'Jan Wu|Yeong-Jian|YJ|', 'Lin|Jing-Chi|JC|', 'Lu|Ling Ying|LY|', 'Wu|Jianming|J|']
D000328:Adult D044466:Asians D015415:Biomarkers D005260:Female D005787:Gene Frequency D020022:Genetic Predisposition to Disease D005838:Genotype D006239:Haplotypes D006801:Humans D007372:Interferons D007378:Interleukins D008180:Lupus Erythematosus, Systemic D008181:Lupus Nephritis D008297:Male D008875:Middle Aged D020641:Polymorphism, Single Nucleotide D013624:Taiwan D055815:Young Adult
Lupus nephritis Systemic lupus erythematosus Interferon λ