The Influence of Genetic Variation in Fcγ RIIIb (NA1/NA2) on Neutrophil Specific Granule Release

Academic Article

Abstract

  • Two classes of receptors for the Fcγ region of IgG, Fcγ RIIa and Fcγ RIIIb, both of which exist in two allelic forms, are expressed on human neutrophils. These receptors play an important role in the development of inflammatory responses and are important mediators of neutrophil activation in ANCA associated vasculitis. Fcγ RIIIb has two allelic forms, the NA1 and the NA2 allele. Neutrophil Fcγ R phagocytosis has been previously reported to be greater in Fcγ RIIIb-NA1/1 donors compared to Fcγ RIIIb-NA2/2 donors, however, no data are available on the influence of these alleles on Fcγ RIIIb induced neutrophil degranulation responses. In this study, we evaluated the magnitude of release of specific granules form neutrophils induced by Fcγ RIIIb crosslinking (XL) comparing Fcγ RIIIb-NA1/1 donors and Fcγ R-NA2/2 donors. Using a whole blood assay system, we quantified release of specific granule release by determining the surface expression of CD66b by flow cytometry. Fcγ RIIIb XL on neutrophils from Fcγ RIIIb-NA1/1 donors resulted in greater degranulation relative to NA2/2 donors (%increase in CD66b expression: 145.0±1.6% vs. 123.0±2.6% for NA1/1 vs. NA2/2 donors, p=0.005, 4 pairs). Degranulation induced by Fcγ RIIa XL was the same in these donors. These observations demonstrate that the Fcγ RIIIb-NA1 allele possesses greater functional activity relative to the Fcγ RIIIb-NA2 allele, suggesting that the greater functional activity of the Fcγ RIIIb-NA1 allele may be a factor in the development of clinical activity in ANCA-associated vasculitis.
  • Author List

  • Tanaka S; Edberg JC; Kimberly RP; Kondo H
  • Start Page

  • 70
  • End Page

  • 77
  • Volume

  • 31
  • Issue

  • 2