HLA-C and -Bw typing of couples with unexplained recurrent miscarriages

There is now evidence that the classical HLA class I molecule HLA-C is expressed on extravillous trophoblasts together with non-classical HLA-G molecules. Since clones of NK-cells are inhibited differently by supertypic epitopes associated with HLA-C and -B alleles we found it of interest to study HLA-C and -Bw polymorphism in 35 couples with recurrent miscarriage and 30 control couples with normal fecundity. All HLA assignments were undertaken by DNA techniques. The distribution of HLA-C alleles or the HLA-C associated supertypic epitopes recognized by NK1 or NK2 clones was not significantly different between patients and controls. The distribution of couples according to the number of NK1 and NK2 epitopes in the couple was similar in patients and controls. With respect to the HLA-Bw epitopes recognized by NKB1 clones, in 46% of the couples with recurrent miscarriage none of the spouses carried the HLA-Bw4 epitope compared with only 17% of the control couples (P < 0.02). It is concluded that the HLA-Bw4 epitope is carried more frequently by couples with normal fecundity than couples with recurrent miscarriage. The fetuses of couples with recurrent miscarriage are thus expected to lack expression of HLA-Bw4 epitopes on the trophoblast more often than fetuses of normal couples which might be of importance for the inhibition of NK-cell mediated antitrophoblast cytotoxicity.