Immunogenicity of and immune response to the human platelet antigen Zwa is strongly associated with HLA-B8 and DR3.

In a prospective study the immunogenicity of the Zwa antigen during gestation was investigated. Twenty-six out of 1,211 pregnant women were Zwa negative (2.15%). In 2 out of 23 Zwa negative mothers who delivered Zwa positive children, an antibody to Zwa was detected. To determine the relationship between the immune response of pregnant women towards Zwa and the MHC, the phenotype frequencies of HLA-A, B, C, DR, and complement BF, C2, C4A, C4B allotypes of "non-responders" without detectable Zwa antibodies (N = 20) were compared with a group of "responders", i.e. Zwa negative mothers giving birth to Zwa positive children with typical neonatal alloimmune thrombocytopenia (NAIT; N = 39) and with a normal control population. When compared to the normal control group, "non-responders" showed a significant increase of the DRw6 frequency, whereas in the "responders" group HLA-A1, B8, DR3, and C4A*QO were significantly elevated. If "non-responders" and "responders" were directly compared, only B8 and DR3 remained significantly different. The strongest association with a hypothetical immune response gene appeared to exist with DR3.