Journal article

Publication year: 2020

Pages: 815-821

Journal: Transfusion

Volume number: 60

Issue number: 4

ISSN: 0041-1132

eISSN: 1537-2995

Open access status: Hybrid

DOI Link: https://doi.org/10.1111/trf.15707

Publisher: Wiley

Abstract: 

BACKGROUND Neutrophil specific Fc gamma receptor IIIb (CD16b) is a low-affinity IgG receptor. Its polymorphic variants are associated with human neutrophil antigens (HNA). HNA-1a and HNA-1b differ in four amino acids. Immunization can lead to the production of alloantibodies. The exact contribution of four amino acid exchanges for the formation of HNA-1a, -1b epitopes is currently unknown.

STUDY DESIGN AND METHODS Permutation of each polymorphic amino acid from wild-type CD16b cDNA constructs was performed and expressed on HEK293 cells. All 16 receptor variants were produced and tested against 19 well-characterized HNA antisera in an antigen capture assay.

RESULTS Analyzing the reaction pattern revealed that anti-HNA-1a antibodies can bind whenever asparagine (N) is present in position 65, regardless of the three other positions (CD16b *N**). Anti-HNA-1b antibodies can bind when serine (S) is present in position 36 (CD16b S***), when N is present in position 82 (CD16b **N*), or both (CD16b S*N*). CD16b variants with N65 and S36 and/or N82 (such as CD16b SNN*) bind both, anti-HNA-1a and anti-HNA-1b alloantibodies. If these specific amino acids are missing (as in CD16b RSD*), no antibodies will bind.

CONCLUSION Whereas the primary structure of HNA-1a and HNA-1b usually differs in four amino acids, epitope composition is not "antithetical". N65 alone determines the presence of HNA-1a, and S36 and/or N82 determine the presence of HNA-1b. Amino acid 106 does not participate in epitope formation. Our findings are of specific relevance when a HNA-1 phenotype is predicted from a genotype.

Harvard Citation style: Sachs, U., Radke, C., Bein, G., Grabowski, C., Simtong, P., Bux, J., et al. (2020) Primary structure of human neutrophil antigens 1a and 1b, Transfusion, 60(4), pp. 815-821. https://doi.org/10.1111/trf.15707

APA Citation style: Sachs, U., Radke, C., Bein, G., Grabowski, C., Simtong, P., Bux, J., Bayat, B., & Reil, A. (2020). Primary structure of human neutrophil antigens 1a and 1b. Transfusion. 60(4), 815-821. https://doi.org/10.1111/trf.15707