title: Fcgamma receptor polymorphisms in Wegener's granulomatosis: risk factors for disease relapse.
abstract: OBJECTIVE
  Several studies have recently identified polymorphisms of receptors for the Fc fragment of IgG (FcgammaR) as genetic factors influencing susceptibility to multiple autoimmune and infectious diseases. This genetic predisposition could also influence the expression of Wegener's granulomatosis (WG), a systemic autoimmune disease with chronic nasal carriage of Staphylococcus aureus as an important risk factor for disease relapses. Therefore, we analyzed 3 functional FcgammaR polymorphisms from 91 patients with WG and 154 controls for a possible relationship with disease expression and occurrence of relapses.
  
  
  METHODS
  FcgammaR phenotypes were determined using amplification of FcgammaR-genomic regions in allotype-specific polymerase chain reactions. Of particular interest in the analysis were 2 allotypic forms of FcgammaRIIa (R131 or H131) and 2 allotypic forms of FcgammaRIIIa (V158 or F158), all of which are functionally different.
  
  
  RESULTS
  Analysis of FcgammaR phenotypes demonstrated that patients with WG were more prone to disease relapse in the first 5 years after diagnosis if they were homozygous for both the R131 form of FcgammaRIIa and the F158 form of FcgammaRIIIa (relative risk 3.3, 95% confidence interval 1.6-6.8). These polymorphisms are both associated with decreased FcR-mediated clearance, which may be relevant to the chronic nasal carriage of S aureus.
  
  
  CONCLUSIONS
  Both the R/H131 polymorphism of FcgammaRIIa and the V/F158 polymorphism of FcgammaRIIIa represent heritable risk factors for the development of disease relapses in WG.
authors.affiliation: University Hospital, Groningen, The Netherlands.
authors.forename: H M
authors.initials: HM
authors.lastname: Dijstelbloem
authors.forename: R H
authors.initials: RH
authors.lastname: Scheepers
authors.forename: W W
authors.initials: WW
authors.lastname: Oost
authors.forename: C A
authors.initials: CA
authors.lastname: Stegeman
authors.forename: W L
authors.initials: WL
authors.lastname: van der Pol
authors.forename: W J
authors.initials: WJ
authors.lastname: Sluiter
authors.forename: C G
authors.initials: CG
authors.lastname: Kallenberg
authors.forename: J G
authors.initials: JG
authors.lastname: van de Winkel
authors.forename: J W
authors.initials: JW
authors.lastname: Tervaert
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D005838:Genotype; D014890:Granulomatosis with Polyangiitis / Q000175:diagnosis / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011110:Polymorphism, Genetic; D017452:Receptors, IgG / Q000235:genetics*; D012008:Recurrence; D012307:Risk Factors
chemical_list: D017452:Receptors, IgG