New Horizons in the Evaluation and Treatment of Recurrent Pregnancy Loss

  • Alan E. Beer
  • Joanne Y. H. Kwak
  • Alice Gilman-Sachs
  • Kenneth D. Beaman
Part of the Serono Symposia, USA book series (SERONOSYMP)

Abstract

During the past 15 years we have evaluated couples with unexplained recurrent spontaneous abortion (RSA), couples with normal pregnancies, and women who electively terminate their pregnancies early in gestation and have found major differences in the alloimmune and autoimmune status in women with unexplained RSA (1–3). In studies of over 1500 couples in this latter category we have shown (i) a higher incidence of HLA-DR and HLA-DQ antigen sharing compared to fertile controls (4); (ii) a higher incidence of HLA-DR and -DQ homozygosity in the male partners (5); (iii) a markedly decreased level of maternal alloantibody to paternal T and B lymphocytes compared to fertile control couples (2, 6); (iv) a strikingly higher incidence of antiphospholipid antibodies to phosphatidylserine (PS), phosphatidylinositol (PI), phosphatidylglycerol (PG), and cardiolipin (CL) that increases in incidence and titer with each subsequent pregnancy loss in three distinct populations of women studied (United States, Kuwait, and Colombia) (3, 7); and (v) an 89% incidence of subsequent pregnancy loss following lymphocyte immune therapy in autoimmune women untreated for the autoimmune abnormalities (2).

Keywords

Arthritis Aspirin Heparin Hunt Prednisone 

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References

  1. 1.
    Beer AE, Quebbeman JF, Ayers JWT, Haines RF. Major histocompatibility complex antigens, maternal and paternal immune responses, and chronic habitual abortions in human. Am J Obstet Gynecol 1981;141:987–99.PubMedGoogle Scholar
  2. 2.
    Kwak JYH, Gilman-Sachs A, Beaman KD, Beer AE. Reproductive outcome in women with recurrent spontaneous abortions of alloimmune and autoimmune etiologies;pre vs post conception treatment. Am J Obstet Gynecol 1992;166:1975–87.Google Scholar
  3. 3.
    Kwak JYH, Gilman-Sachs A, Beaman KD, Beer AE. Autoantibodies in women with primary recurrent spontaneous abortion of unknown etiology. J Reprod Immunol 1992;22:15–31.PubMedCrossRefGoogle Scholar
  4. 4.
    Beer AE, Zhu X, Semprini AE, Quebbeman JF. 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. In:Talwar GP, ed. Immunological approaches to contraception and promotion of fertility. Plenum, 1986:393–406.Google Scholar
  5. 5.
    Kwak-Kim JYH, Beaman KD, Gilman-Sachs A, Kerns K, Ober C, Beer AE. HLA immunogenetic evaluation of couples with primary and secondary recurrent spontaneous abortions. Soc Gynecologic Investigation, 37th annu meet. St. Louis, Missouri, 1990:340.Google Scholar
  6. 6.
    Lubinski J, Vrodoljak VJ, Beaman KD, Kwak JYH, Beer AE, Gilman-Sachs A. Characteristics of antibodies induced by paternal lymphocyte immunization in couples with recurrent spontaneous abortion. J Reprod Immunol 1993.Google Scholar
  7. 7.
    Bahar AM, Kwak JYH, Beer AE, et al. Antibodies to phospholipids and nuclear antigens in non-pregnant women with unexplained spontaneous recurrent abortions. J Reprod Immunol 1993.Google Scholar
  8. 8.
    Session A, Horwitz A. Myoblast aminophospholipid asymmetry differs from that of fibroblasts. FEBS Lett 1981;134:75–8.CrossRefGoogle Scholar
  9. 9.
    Session A, Horowitz A. Differentiation related differences in the plasma membrane phospholipid asymmetry of myogenic and fibrogenic cells. Biochim Biophys Acta 1983;728:103–11.CrossRefGoogle Scholar
  10. 10.
    Ehrlich HA, Bugawan TL. Principles and applications for DNA amplification. In:Erlich HA, ed. PCR technology. New York:Stockton Press, 1989:193–208.Google Scholar
  11. 11.
    Beer AE, Kwak JYH, Beaman KD, Gilman-Sachs A. Antiphospholipid antibodies in women with recurrent pregnancy losses:elicitation, expression and therapy. In:Dondero F, Johnson PM, eds. Reproductive immunology;vol 79. Rome:Raven Press, 1993:265–72.Google Scholar
  12. 12.
    Kwak JYH, Barini R, Gilman-Sachs A, Beaman KD, Beer AE. Down regulation of maternal antiphospholipid antibodies during early pregnancy and pregnancy outcome. Soc Gynecologic Investigation, 40th annu meet. Toronto, Canada, 1993:107.Google Scholar
  13. 13.
    Loke YW, Kina A, Chumbley G, Holmes N. Does HLA-G influence trophoblast susceptibility to lysis by decidual large granular lymphocytes? In:Dondero F, Johnson PM, eds. Reproductive immunology;vol 79. Rome:Raven Press, 1993:145–8.Google Scholar
  14. 14.
    Sanders SK, Giblin PA, Kavathas P. Cell-cell adhesion mediated by CD8 and human histocompatibility leukocyte antigen G, a nonclassical major histocompatibility complex class 1 molecule on cytotrophoblasts. J Exp Med 1991;174:737–40.PubMedCrossRefGoogle Scholar
  15. 15.
    Bulmer JN. Decidual leucocytes in normal and pathological human pregnancy. In:Dondero F, Johnson PM, eds. Reproductive immunology;vol 79. Rome:Raven Press, 1993:129–32.Google Scholar
  16. 16.
    Johnson PM, Deniz G, McLaughlin PJ, Hampson J, Christman SE. Functional properties of cloned CD3-decidual leucocytes and loss-affinity cytokine receptor expression on human trophoblast. In:Dondero F, Johnson PM, eds. Reproductive immunology;vol 79. Rome:Raven Press, 1993:141–4.Google Scholar
  17. 17.
    Reed E, Beer AE, King DW, Suciu-Foca N. The alloantibody response of pregnant women and its suppression by soluble HLA antigens and antiidiotypic antibodies. J Reprod Immunol 1991;28:103–13.Google Scholar
  18. 18.
    Wegman TG. Fetal protection against abortion:is it immunosuppression or immunostimulation? Annu Rev Immunol 1984;135D:309–12.Google Scholar
  19. 19.
    Clark DA, Chaput A, Tutton B. Active suppression of host versus graft reaction in pregnant mice, VII. Spontaneous abortion of CBA x DBA/2 fetuses in the uterus of CBA/J mice correlates with deficient non-T suppressor cell activity. J Immunol 1986;136:1668–74.PubMedGoogle Scholar
  20. 20.
    Chaouat G, Menu E, Clark DA, Dy M, Minkowski M, Wegmann TG. Control of fetal survival in CBA x DBA/2 mice by lymphokine therapy. Reprod Fertil 1990;89:447–58.CrossRefGoogle Scholar
  21. 21.
    Beer AE, Kwak JYH. Recurrent spontaneous abortions immunological evaluation. In:Current therapy in obstetrics and gynecology. Philadelphia:Saunders, 1993.Google Scholar
  22. 22.
    Galstian A, Beer AE, Roberts JM, Coulam CB, Faulk WP Immunology of preeclampsia. In:Coulam CB, Faulk WP, McIntyre JA, eds. Immunological obstetrics;vol 1. NY and London:W.W. Norton, 1992:502–16.Google Scholar
  23. 23.
    Branch W, Scott JR, Kochenour NK, Hershgold E. Obstetric complications associated with the lupus anticoagulant. N Engl J Med 1985;313:1322–6.PubMedCrossRefGoogle Scholar
  24. 24.
    Lockshin MD, Qamar T, Druzin ML. Antibody to cardiolipin, lupus anticoagulant and fetal death. J Rheumatol 1987;14:259–62.PubMedGoogle Scholar
  25. 25.
    Haas GGJ, Kubota K, Quebbeman JF, Jijon A, Menge AC, Beer AE. Circulating antisperm antibodies in recurrently aborting women. Fertil Steril 1986;43:209–15.Google Scholar
  26. 26.
    Nelson JL, Hughes KA, Smith AG, Nisperos BB, Branchaud AM, Hansen JA. Maternal-fetal disparity in HLA class II alloantigens and the pregnancy-induced amelioration of rheumatoid arthritis. N Engl J Med 1993;329:466–71.PubMedCrossRefGoogle Scholar
  27. 27.
    Billingham RE, Beer AE. Reproductive immunology:past, present, and future. Perspect Biol Med 1984;27:259–75.PubMedGoogle Scholar
  28. 28.
    Ness RB, Harris T, Cobb J, et al. Number of pregnancies and the subsequent risk of cardiovascular disease. N Engl J Med 1993;328:1528–33.PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag New York, Inc. 1994

Authors and Affiliations

  • Alan E. Beer
  • Joanne Y. H. Kwak
  • Alice Gilman-Sachs
  • Kenneth D. Beaman

There are no affiliations available

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