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

Ji Yih Chen, Chin Man Wang, Tai Di Chen, Yeong Jian Jan Wu, Jing Chi Lin, Ling Ying Lu, Jianming Wu

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11 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article number193
JournalArthritis Research and Therapy
Volume20
Issue number1
DOIs
StatePublished - Aug 29 2018

Bibliographical note

Funding Information:
This study was supported by funding from the Chang Gung Memorial Hospital (CMRPG3B1823 and CMRPG3E05313) and the Ministry of Science and Technology (103-2314-B-182-067-MY3). JWu’s work was supported by a NIH grant (AI125729).

Keywords

  • Interferon λ
  • Lupus nephritis
  • Systemic lupus erythematosus

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