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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. Electronic supplementary material The online version of this article (10.1186/s13075-018-1683-z) contains supplementary material, which is available to authorized users.

Background HCMV phosphoprotein 65 (HCMVpp65) is a putative immunogen that acts as an accelerator, inducing autoantibody and exacerbating autoimmune response in susceptible animals. The immunity to pp65336-439 instigates autoimmunity, suggesting that pp65336-439 contains crucial B cell epitope(s) for the development of nephritis. This study narrowed down the target epitope to pp65422-439 for immunization of BALB/c mice and mapping of B cell epitope. Methods The target epitope pp65422-439 reactivity and B cell epitope mapping was examined in serum from pp65422-439-immunized mice and patients with systemic lupus erythematosus (SLE). Kidney tissue from immunized mice was examined for signs of immune complex nephritis. Results Anti-pp65422-439 antibody in serum either from patients with SLE or from pp65422-439-immunized mice exhibited cross-reactivity to several nuclear components such as double-stranded DNA (dsDNA). Moreover, the pp65422-439-immunized mice developed initial signs of glomerulonephritis such as deposition of immunoglobulin G/M (IgG/IgM) and third complement component (C3). With B cell epitope mapping by pp65422-439-derived decapeptides, one dominant epitope, pp65428-437, was identified in serum from pp65422-439-immunized mice and patients with SLE with anti-pp65422-439 antibody. Epitope spreading from pp65428-437 to pp65430-439 was found in pp65422-439-immunized mice in which we generated monoclonal antibodies to pp65425-434 and pp65430-439. However, dsDNA positive reactivity was exclusively observed in Crithidia luciliae stains with pp65430-439-reactive monoclonal antibody. Additionally, we observed the amelioration of autoimmunity following the elevation of IgM targeting pp65428-437. Conclusions Our data suggest that pp65428-437 may be an autoimmune or lupus-prone B cell epitope and may catalyze further epitope spreading for inducing autoantibodies in lupus-susceptible individuals. Electronic supplementary material The online version of this article (doi:10.1186/s13075-017-1268-2) contains supplementary material, which is available to authorized users.