Molecular basis of human neutrophil antigen 2 ( HNA ‐2) expression

Abstract

HNA ‐2 is a neutrophil‐specific antigen located on GPI ‐anchored glycoprotein CD 177. HNA ‐2 is absent from the neutrophil surface of 3–5% of normal individuals, known as HNA ‐2 null individuals. The exposure of HNA ‐2 null individuals to HNA ‐2‐positive neutrophils during pregnancy, transfusion or transplantation induces immunization against HNA ‐2 and production of isoantibodies. These isoantibodies are involved in the mechanism of neonatal alloimmune neutropenia ( NAIN ), transfusion‐related acute lung injury ( TRALI ) and graft rejection. The presence of CD 177 on a neutrophil surface of HNA ‐2‐positive individuals follows a bimodal expression that categorizes the circulating neutrophils into HNA ‐2‐positive and HNA ‐2‐negative subsets. The lack of HNA ‐2 (in HNA ‐2 null individuals) is associated with the presence of a missense mutation, CD 177*c.787A>T in exon 7 (Lysine 263 Stop) of the CD 177 gene. This mutation alone or in combination with CD 177*c.997delG has been introduced as the main reason for the absence of CD 177 in HNA ‐2 null individuals. A pseudogene ( CD 177 P1 ) is located downstream of the CD 177 gene. The conversion of exon 7 of CD 177P1 into CD 177 is responsible for the generation of the CD 177*c.787A>T missense mutation. Genotyping has identified HNA ‐2 null individuals that are heterozygous for the CD 177*c.787A>T mutation without CD 177*c.997delG, indicating the presence of a complementary mechanism regulating CD 177 expression. In HNA ‐2 null individuals and those with atypical CD 177 expression, a CD 177*c.1291G>A polymorphism in combination with CD 177*c.787A>T has been recently described. Altogether, these data indicate a complex compound mechanism for the regulation of CD 177 expression on the neutrophil surface. This manuscript will summarize recent findings on CD 177 expression and highlights the CD 177 functions on neutrophil surface.