Neutrophil FcgammaRIIIb allelic polymorphism in anti-neutrophil cytoplasmic antibody (ANCA)-positive systemic vasculitis.
Neutrophils constitutively express FcgammaRIIa and FcgammaRIIIb receptors. Both receptors exhibit allelic variants which have different quantitative functional capacities: the biallelic FcgammaRIIa-R131 and -H131 alleles, and the neutrophil antigen (NA) NA1/NA2 alleles. ANCA activation of neutrophils requires ligation of FcgammaRIIa receptor, but recent data have shown that ANCA can also bind FcgammaRIIIb receptor. The aim of this study was to determine whether the FcgammaRIIIb polymorphism was a risk factor for the development of ANCA-associated systemic vasculitis, or the associated nephritis. FcgammaRIIIb receptor genotyping was determined by allele-specific polymerase chain reaction. Genomic DNA was extracted from 101 Caucasian patients with ANCA+ vasculitis (of whom 84 had renal disease) and 100 ethnically matched controls. Of the patients with ANCA+ systemic vasculitis, 71 had ANCA with specificity for proteinase 3 and 30 with specificity for myeloperoxidase (MPO). Overall no significant difference in genotype distribution or allele frequencies was found between patients and controls, or between patients with renal disease and controls. However, there was a trend for an increase in homozygosity for the NA1 allele in patients with a vasculitis and this was significant in patients who had anti-MPO antibodies. The FcgammaRIIIb receptor polymorphism is not a major factor predisposing to the development of ANCA+ systemic vasculitis or the associated nephritis. The over-representation of the FcgammaRIIIb homozygous NA1 allele in patients with anti-MPO antibodies may have implications for disease susceptibility.
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Department of Nephrology, Queen Elizabeth Hospital, and Department of Immunology, The Medical School, Birmingham University, Birmingham, UK. W.Y.TSE.1@bham.ac.uk
Abadeh
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D000483:Alleles; D019268:Antibodies, Antineutrophil Cytoplasmic / Q000276:immunology*; D001323:Autoantibodies / Q000276:immunology; D006801:Humans; D009504:Neutrophils / Q000276:immunology; D011110:Polymorphism, Genetic; D017452:Receptors, IgG / Q000235:genetics*; D014657:Vasculitis / Q000235:genetics* / Q000276:immunology*
D019268:Antibodies, Antineutrophil Cytoplasmic; D001323:Autoantibodies; D017452:Receptors, IgG