Parental HLA compatibility, fetal wastage and neural tube defects: evidence for a T/t-like locus in humans.
To test the hypothesis that a locus in or near the human major histocompatibility complex (HLA) contributes to both involuntary fetal loss and neural tube defects (NTD), we evaluated sharing of antigens of the HLA-A, HLA-B, or HLA-DR loci of couples who had three or more first-trimester spontaneous abortions or who had a child with an NTD (myelomeningocele or anencephaly). HLA-A antigen sharing was increased in couples with three or more spontaneous abortions and in couples who had an anencephalic fetus, when compared with couples who had three or more pregnancies and no fetal loss. Increased sharing of antigens at the HLA-A and B loci was not seen in the entire group of couples with children with myelomeningocele, but was found in the subgroup of 36 couples whose child had a lumbar myelomeningocele. An increase in HLA-DR sharing was not seen in any group or subgroup when compared with the control couples. Among the aborting couples, increased sharing was not restricted to the couples who had no term pregnancies, but was also found in the couples whose fetal losses occurred after one or more normal term pregnancies. These results are consistent with the hypothesis that a locus on the HLA-A side of the HLA-DR locus contributes to some fetal loss and susceptibility to NTD. This model is proposed as an alternative to the hypothesis that the maternal immune response to paternal major histocompatibility complex (MHC) antigens is the basis for increased HLA sharing in couples with fetal wastage.
D000022:Abortion, Spontaneous / Q000235:genetics / Q000276:immunology*; D002874:Chromosome Mapping; D005260:Female; D006680:HLA Antigens / Q000235:genetics*; D015234:HLA-A Antigens; D015235:HLA-B Antigens; D006684:HLA-DR Antigens; D000949:Histocompatibility Antigens Class II / Q000235:genetics; D006801:Humans; D007231:Infant, Newborn; D008285:Major Histocompatibility Complex; D008297:Male; D009436:Neural Tube Defects / Q000235:genetics / Q000276:immunology*; D011247:Pregnancy; D011261:Pregnancy Trimester, First
D006680:HLA Antigens; D015234:HLA-A Antigens; D015235:HLA-B Antigens; D006684:HLA-DR Antigens; D000949:Histocompatibility Antigens Class II