The expression of NA antigens in people with unusual Fc gamma receptor IIIgenotypes

BACKGROUND: The Fc gamma receptor IIIb (Fc gamma RIIIB) genes that encode n eutrophil-specific antigens NAI and NA2 differ at 5 nucleotides (nts); in 4 , the result is an amino acid (AA) difference between the two alleles. The role of each of these differences in antigen expression is not known. Perso ns with Fc gamma RIIIB genes that differ from NA1-Fc gamma RIIIB and NA2-Fc gamma RIIIB by 1 nt have been described. This study compared NAI and NA2 e xpression on granulocytes in persons with variant Fc gamma RIIIB genes and in healthy blood donors. STUDY DESIGN AND METHODS: Reactions of NA1- and NA2-specific MoAbs and allo antibodies with granulocytes were assessed by flow cytometry in 74 healthy blood donors and 6 persons with known variant Fc gamma RIIIB genes. The gra nulocytes were tested with 1 NAI-specific MoAb, 1 NAP-specific MoAb, 4 NA1- specific alloantibodies, and 4 NAP-specific alloantibodies. RESULTS: Analysis of granulocytes from persons with variant NA genotypes fo und that single-base substitutions in Fc gamma RIIIB at 141 and at 349 are important in NAI expression and those at 227 and 277 are important in NA2 e xpression. Among blood donors, neither age, sex, nor race affected the expr ession of NA1 or NA2. The NAP-specific MoAb reacted more intensely with gra nulocytes from NAP-double-dose cells than with those from NA-single-dose ce lls, but this was not true for the NAP-specific alloantibodies. There was n o difference in the reactions of the NA1-specific MoAbs and alloantibodies with donor samples of known NA1-double-dose or NA-single-dose cells. The in tensity of reactions of both the NA1- and NAP-specific MoAbs and alloantibo dies were strongly correlated on double-dose cells but not on single-dose c ells. In fact, granulocytes from 74 healthy blood donors, phenotyped as NA- single-dose with the MoAbs, were phenotyped as NAP-double-dose with the all oantibodies. Variations in Fc gamma RIIIB are common in blacks, but 5 of th e 6 donors were white. These results suggest that Fc gamma RIIIB variations may be common in both whites and blacks. CONCLUSIONS: NA2 expression is affected by polymorphisms in Fc gamma RIIIB2 27 and Fc gamma RIIIB 277, both of which are involved in an Fc gamma RIIIb N-glycosylation site. Polymorphisms in Fc gamma RIIIB at 141 and 349 appear more important to NAI expression.