Habitual Abortion: Parental Sharing of HLA Antigens, Absence of Maternal Blocking Antibody, and Suppression of Maternal Lymphocytes

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Abstract
The immunologic responsiveness of eight women who habitually abort has been investigated. All shared an HLA‐A or B antigen with their husbands. Sharing of an HLA‐DR antigen was found in seven couples, one of which also had a second DR antigen in common. The probability for this high frequency of HLA‐DR sharing is negligible (p = 0.0004), as calculated from the antigen frequencies among Europeans. Cells from the woman with two shared DR antigens displayed a minor response to her husband's cells but reacted strongly to control cells, whereas the other women's cells reacted normally to cells from both their husbands and controls in one‐way mixed lymphocyte culture (MLC). Only minor cytotoxicity was displayed by women's cells in a direct cell‐mediated lympholysis (CML) assay, but they mounted normal cytotoxic responses against both husbands' cells and control cells in an amplified CML assay. The sera from six of the habitually aborting women displayed no blocking activity in one‐way MLC, and seven of them had no cytotoxic antibodies. Cells from all habitual aborters were suppressed in two‐way MLC by cells from husbands and most controls. We hypothesize that increases in HLA compatibility between mother and fetus and in maternal susceptibility to suppressive influences are in some way linked to a deficiency in the development of anti‐fetal antibody during pregnancy. As a consequence, the fetus may be deprived of the protection by maternal blocking antibody, which may allow maternal cytotoxic reactions to cause abortion.