title: Low copy number of the Fc-γ receptor 3B gene FCGR3B is a risk factor for primary Sjogren's syndrome.
abstract: 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).
  
  
  CONCLUSIONS
  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.affiliation: Department of Rheumatology, Basil Hetzel Institute, The Queen Elizabeth Hospital, Adelaide, Australia.
authors.forename: Johannes C
authors.initials: JC
authors.lastname: Nossent
authors.forename: Maureen
authors.initials: M
authors.lastname: Rischmueller
authors.forename: Sue
authors.initials: S
authors.lastname: Lester
mesh_terms: D001323:Autoantibodies / Q000097:blood; D016022:Case-Control Studies; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D005260:Female; D058851:GPI-Linked Proteins / Q000235:genetics; D018628:Gene Dosage / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D008297:Male; D008875:Middle Aged; D017452:Receptors, IgG / Q000235:genetics*; D012217:Rheumatoid Factor / Q000097:blood; D012234:Rho Factor / Q000276:immunology; D012307:Risk Factors; D012859:Sjogren's Syndrome / Q000097:blood / Q000235:genetics*
chemical_list: D001323:Autoantibodies; C428200:FCGR3B protein, human; D058851:GPI-Linked Proteins; D007074:Immunoglobulin G; D017452:Receptors, IgG; D012234:Rho Factor; D012217:Rheumatoid Factor