Feto-maternal HLA compatibility does not have a major influence on human pregnancy except for lymphocytotoxin production.

Several studies have supported the hypothesis that the maternal immune response to incompatible paternal HLA antigens present on the conceptus may influence pregnancy outcome. In order to relate feto-maternal histocompatibility directly to pregnancy course and characteristics, complete HLA-A, B and DR types were obtained from 132 healthy family groups consisting of mothers, fathers and neonates. The distribution of feto-maternal HLA compatibility was heavily skewed towards incompatibility, with 90% of fetuses being mismatched at 2 or 3 loci. There was no segregation distortion of paternal haplotypes, however, and the number of feto-maternal mismatches was close to that expected theoretically. More than 2% of the neonates were perfectly HLA-A, B and DR compatible with their mothers. The degree of feto-maternal HLA disparity showed no significant correlation with sex of neonate, birthweight, placental weight, maternal plasma alpha-fetoprotein or parity of the mother. Feto-maternal HLA disparity did, however, correlate significantly with maternal lymphocytotoxin production, even after allowance was made for parity (P less than 0.01). We conclude that feto-maternal HLA compatibility per se does not have a major influence on pregnancy outcome, and in particular is unlikely to predispose to spontaneous abortion; so an absence of antigen sharing between spouses experiencing recurrent spontaneous abortions should not be regarded in itself as a contraindication to offering immunotherapy to such couples.