OBJECTIVE: Immune complexes play an important role in the pathogenesis of primary Sjögren's syndrome (pSS). Crosslinking of the neutrophil-specific Fc-γ receptor 3b (FCGR3B) facilitates immune complex clearance, and copy number variation (CNV) of the FCGR3B gene is known to reduce the uptake, and potentially clearance, of circulating immune complexes. Our objective was to determine whether FCGR3B CNV is a risk factor for pSS. METHODS: This was a cross-sectional study of patients with established pSS (n = 174) and population-matched controls (n = 162). FCGR3B CNV was determined by a quantitative real-time polymerase chain reaction assay, using genomic DNA as template and Taqman chemistry. Reactions were performed as a duplex, with RNAse P as the reference gene. Clinical and serological data were analyzed for their association with FCGR3B copy number (CN). RESULTS: Low FCGR3B CN (< 2 copies) was a risk factor for pSS in this cohort (p = 0.016), and combined results from this and a previous study yielded an overall OR of 2.3 (95% CI 1.3, 3.9, p = 0.003). Among patients with pSS in our cohort, low FCGR3B CN was not associated with anti-Ro ± La autoantibodies, but was associated with lower rheumatoid factor titers (p = 0.001) and serum IgG levels (p = 0.031). CONCLUSION: We confirmed that, similarly to other systemic autoimmune diseases, FCGR3B CN is a genetic susceptibility factor for pSS. As in rheumatoid arthritis, the mechanism does not appear to be related to seropositivity for characteristic autoantibodies.
OBJECTIVE: Immune complexes play an important role in the pathogenesis of primary Sjögren's syndrome (pSS). Crosslinking of the neutrophil-specific Fc-γ receptor 3b (FCGR3B) facilitates immune complex clearance, and copy number variation (CNV) of the FCGR3B gene is known to reduce the uptake, and potentially clearance, of circulating immune complexes. Our objective was to determine whether FCGR3B CNV is a risk factor for pSS. METHODS: This was a cross-sectional study of patients with established pSS (n = 174) and population-matched controls (n = 162). FCGR3B CNV was determined by a quantitative real-time polymerase chain reaction assay, using genomic DNA as template and Taqman chemistry. Reactions were performed as a duplex, with RNAse P as the reference gene. Clinical and serological data were analyzed for their association with FCGR3B copy number (CN). RESULTS: Low FCGR3B CN (< 2 copies) was a risk factor for pSS in this cohort (p = 0.016), and combined results from this and a previous study yielded an overall OR of 2.3 (95% CI 1.3, 3.9, p = 0.003). Among patients with pSS in our cohort, low FCGR3B CN was not associated with anti-Ro ± La autoantibodies, but was associated with lower rheumatoid factor titers (p = 0.001) and serum IgG levels (p = 0.031). CONCLUSION: We confirmed that, similarly to other systemic autoimmune diseases, FCGR3B CN is a genetic susceptibility factor for pSS. As in rheumatoid arthritis, the mechanism does not appear to be related to seropositivity for characteristic autoantibodies.
Authors: Lude Franke; Hanane el Bannoudi; Diahann T S L Jansen; Klaas Kok; Gosia Trynka; Dorothee Diogo; Morris Swertz; Karin Fransen; Rachel Knevel; Javier Gutierrez-Achury; Lisbeth Ärlestig; Jeffrey D Greenberg; Joel Kremer; Dimitrios A Pappas; Alexandros Kanterakis; Rinse K Weersma; Annette H M van der Helm-van Mil; Viktor Guryev; Solbritt Rantapää-Dahlqvist; Peter K Gregersen; Robert M Plenge; Cisca Wijmenga; Tom W-J Huizinga; Andreea Ioan-Facsinay; Rene E M Toes; Alexandra Zhernakova Journal: Eur J Hum Genet Date: 2015-05-13 Impact factor: 4.246
Authors: Robert Makowsky; Howard W Wiener; Travis S Ptacek; Miriam Silva; Aditi Shendre; Jeffrey C Edberg; Michael A Portman; Sadeep Shrestha Journal: Pharmacogenet Genomics Date: 2013-09 Impact factor: 2.089
Authors: Young Ho Lee; Sang-Cheol Bae; Young Ho Seo; Jae-Hoon Kim; Sung Jae Choi; Jong Dae Ji; Gwan Gyu Song Journal: Inflamm Res Date: 2015-09-25 Impact factor: 4.575