HLA antigens and maternal antibodies in allo-immune neonatal thrombocytopenia.

Abstract

Forty mothers who had given birth to children with a clinically probable diagnosis of allo‐immune neonatal thrombocytopenia were typed for ABO, HLA—ABC and Zwa antigens and their sera were investigated with the platelet complement fixation microtest (CFT), the lymphocytotoxic test (LCT), and the platelet suspension immunofluorescence test (PSIFT). Seventeen (43%) of the 40 mothers were Zwa‐negative, which is significantly (p > 10‐10) much more frequent than in controls (2.5%). Anti‐Zwa antibodies could be demonstrated by PSIFT in most of the Zwa‐negative mothers investigated, but in no cases by CFT. The only serum positive by this technique also contained HLA‐antibodies demonstrable by LCT. Lymphocytotoxic antibodies were found in 33% of the cases and this is not different from the frequency observed in normal pregnancies. In ten cases, antibodies of unknown specificity were only detectable by PSIFT. Nine of these mothers were Zwa‐positive and these antibodies may be directed towards platelet specific antigens different from Zwa.Of the Zwa‐negative mothers, 65% were HLA—B8 positive which is significantly (corrected p = 0.02) different from the frequency (25%) of this antigen in controls. This observation definitely confirms a preliminary observation in a small material. In the 23 Zwa‐positive mothers, a borderline increased frequency (43%) of HLA—B8 was found.ABO compatibility between mother and child was not found more often than expected.It is concluded in this study that anti‐Zwa antibodies may account for about half of all cases of AINT, and that PSIFT is a useful method to detect both these antibodies and perhaps other platelet specific antibodies causing AINT. The increased frequency of HLA—B8 in the mothers may reflect the operation of an HLA—B8 linked immune response determinant in the mothers, but may also be explained by the action of an HLA controlled complement variant facilitating destruction of antibody‐coated platelet in the infant.Studies to investigate these possibilities are in progress.