Fcgamma receptor polymorphisms determine the magnitude of in vitro phagocytosis of Streptococcus pneumoniae mediated by pneumococcal conjugate sera

Abstract

Fcgamma receptors show two genetically determined polymorphisms: the biallelic FcgammaRIIa-R131 and -H131 polymorphism and the NA1/NA2 FcgammaIIIb polymorphism. Using 10 pre- and postconjugate vaccination sera from adults, we analyzed in vitro phagocytic capacities of three different combinations of polymorphonuclear leukocyte FcgammaR allotypes: those homozygous for the H131 and NA1 allotype, those homozygous for the R131 and NA2 allotype, and those heterozygous for both receptors. For pre- and postvaccination sera, mean phagocytosis levels for the homozygous H131/NA1 allotype were 4 -fold higher than for the homozygous R131/NA2 allotype. There was a strong and significant correlation between IgG2 ELISA antibody titers and phagocytosis levels for the homozygous H131/NA1 Fcgamma receptor allotype and the heterozygous allotype but not for the homozygous R131/NA2 allotype. There was no relation between IgG1 ELISA titer and phagocytosis level. Apparently the IgG2 antibodies induced are functionally the most important. This may explain the large effect of Fcgamma receptor polymorphisms on in vitro phagocytosis of pneumococci mediated by conjugate antisera.