Pregnancy Outcome in Human Couples with Idiopathic Recurrent Abortions: The Role(s) of Female Serum, Mixed Lymphocyte Culture Blocking Factors, Potentiating Factors, and Local Uterine Immunity Before and After Paternal Leukocyte Immunization
Two hundred-fifty couples with 4.6 ± 2.2 recurrent spontaneous abortions were fully worked up to ensure the absence of medical, genetic, infectious, structural, or a combination of these etiologies known to be associated with recurrent abortion. In addition, all were evaluated immunogenetically. In 67 couples reported here, the female was immunized with paternal leukocytes on two occasions and post-immunization immune response parameters were evaluated. Pregnancy outcome post-immunization can be predicted by analyzing the normal female serum and heat inactivated female serum mixed lymphocyte culture (MLR) blocking factors and potentiating factors with specificity for the male spouse. Women who abort an additional time post-immunization develop leukocytotoxic antibodies with paternal specificity and do not develop MLR blocking factors with specificity for B lymphocytes. Women who deliver a live born child post-immunization develop leukocytotoxic antibodies with less frequency and all develop maternal/anti-paternal specific MLR blocking factors that are not heat inactivatable and are nearly 100% effective in blocking female stimulator/male responder mixed lymphocyte culture reactivity. A subset of women immunized with paternal leukocytes established pregnancies and delivered severely growth retarded infants. In these patients, lymphocytes in the decidua mantling the conceptus were isolated and were found to be cytotoxic and hyperresponsive in MLR to paternal as well as to third party alloantigens.
KeywordsRecurrent Spontaneous Abortion Mixed Lymphocyte Culture Recurrent Abortion Repeat Abortion Fetoplacental Unit
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- 2.Beer A.E., Quebbeman J.F., Semprini A.E., Smouse P.E. and Haines R.F.: Recurrent Abortion: Analysis of the Roles of Parental Sharing of Histocompatibility Antigens and Maternal Immunological Responses to Paternal Antigens. Reproductive Immunology, Isojima S. and Billington W.D. (eds), Elsevier Science Publishers, Amsterdam, 1983.Google Scholar
- 4.Chaouat G: The Riddle of the Fetal Allograft. Ann. Immunol (Inst. Pasteur) 135 D: 301–351, 1984.Google Scholar
- 8.Beer A.E., Quebbeman J.F. and Semprini A.E.: Immunopathological Factors Contributing to Recurrent Spontaneous Abortion In Humans. Edmonds D.K. and Bennett M.J. (eds), Blackwell Scientific Publication, London, 1985, in press.Google Scholar
- 10.Bennett D.: The T Locus of the Mouse Cell. 6: 441–454, 1975.Google Scholar
- 11.Thomas M.L., Harger J.H., Wagener D.K., Rabin B.S., and Gill T.J. III: Sharing and Spontaneous Abortion in Humans. Am. J. Obstet. Gynec, 1985, in press.Google Scholar
- 12.Palm J.: Association of Maternal Genotype and Excess Heterozygosity for Ag-B Histocompatibility Antigens Among Male Rats. Trans. Proc. 1(1): 82–84, 1969.Google Scholar
- 13.Palm J.: Maternal-fetal Interactions and Histocompatibility Antigen Polymorphisms. Trans. Proc. 2: 162–173, 1970.Google Scholar
- 14.Hings I.M. and Billingham R.E.: Splenectomy and Sensitization of Fischer Female Rats Favors Histoincompatibility of R2 Back-cross Progeny. Transplan. Proc. 13: 1253–1255, 1981.Google Scholar
- 15.Michie D. and Anderson N.F.: A Strong Selective Effect Associated With a Histocompatibility Gene in the Rat. Ann. N.Y. Acad. Sci. 129: 88–93.Google Scholar
- 19.Johnson P.M., Barner R.M.R., Risk J.M., Mollay C.M. and Woodrow J.C.: Immunogenetic Studies of Recurrent Spontaneous Abortions in Humans. Expl. Clin. Immunogenet. 2: 77–83, 1985.Google Scholar
- 20.Beer A.E., Semprini A.E., Xiaoyu Z. and Quebbeman J.F.: Pregnancy Outcome in Human Couples With Recurrent Spontaneous Abortions: 1) HLA Antigen Profiles; 2) HLA Antigen Sharing; 3) Female Serum MLR Blocking Factors; and, 4) Paternal Leukocyte Immunization. Exp. Clin. Immunogenet., 1985a, in press.Google Scholar
- 22.Alper C.A., Awdeh Z.L., Roum D.D., Yunis E.J.: Possible Human Analogs of the Murine T/t Complex: Expl. Clin. Immunogenet. 2: 125–136, 1985.Google Scholar