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J Clin Invest. 1997 September 15; 100(6): 1330–1334.
PMCID: PMC508310

Proliferative responses to recall antigens are associated with pregnancy outcome in women with a history of recurrent spontaneous abortion.

Abstract

Maternal tolerance of the fetal hemiallograft suggests that immunomodulation occurs during gestation. Therefore, recurrent spontaneous abortion (RSA) may represent a failure of the immune changes that maintain pregnancy. We hypothesized that fertile women but not women with RSA may lose their immune responses to recall antigens when pregnant. This phenomenon has been seen in immunosuppressed transplant recipients and is associated with graft survival. Therefore, we evaluated proliferative responses to recall antigens in four groups of women: group 1, nonpregnant fertile women with no history of pregnancy loss and at least one prior healthy pregnancy, n = 13; group 2, nonpregnant women with a history of three or more spontaneous abortions, n = 28; group 3, healthy pregnant women between 6 and 9 wk of gestation without a history of prior pregnancy loss, n = 15; and group 4, pregnant women between 6 and 9 wk of gestation, with a history of RSA, n = 22. Proliferative responses of peripheral blood leukocytes to the recall antigens influenza and tetanus, alloantigens, and phytohemagglutinin were determined prospectively. Positive responses (stimulation index > 3) to recall antigens (a response to either influenza or tetanus was considered positive) were as follows: group 1 (nonpregnant fertile women), 11/13 (85%); group 2 (nonpregnant RSA women), 24/28 (86%); group 3 (pregnant fertile women), 4/15 (27%) (P </= 0.007); and group 4 (pregnant RSA women), 13/22 (59%) (P = 0.032) [corrected]. In group 4, there was 100% fetal survival in the nine women who lost responsiveness to recall antigens; however, in the 13/22 patients who responded to recall antigens, 9/13 (69%) had a repeat spontaneous abortion. These findings suggest that immunosuppression, indirectly measured by proliferation to recall antigens, is necessary for early pregnancy maintenance. Furthermore, this approach may be useful for predicting pregnancy outcome for women with RSA and may provide a useful means for designing and monitoring therapies.

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Selected References

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  • Stirrat GM. Recurrent miscarriage. II: Clinical associations, causes, and management. Lancet. 1990 Sep 22;336(8717):728–733. [PubMed]
  • Sargent IL. Maternal and fetal immune responses during pregnancy. Exp Clin Immunogenet. 1993;10(2):85–102. [PubMed]
  • Tafuri A, Alferink J, Möller P, Hämmerling GJ, Arnold B. T cell awareness of paternal alloantigens during pregnancy. Science. 1995 Oct 27;270(5236):630–633. [PubMed]
  • Klipple GL, Cecere FA. Rheumatoid arthritis and pregnancy. Rheum Dis Clin North Am. 1989 May;15(2):213–239. [PubMed]
  • Nelson JL. Maternal-fetal immunology and autoimmune disease: is some autoimmune disease auto-alloimmune or allo-autoimmune? Arthritis Rheum. 1996 Feb;39(2):191–194. [PubMed]
  • Petri M, Howard D, Repke J. Frequency of lupus flare in pregnancy. The Hopkins Lupus Pregnancy Center experience. Arthritis Rheum. 1991 Dec;34(12):1538–1545. [PubMed]
  • Rankin EC, Choy EH, Kassimos D, Kingsley GH, Sopwith AM, Isenberg DA, Panayi GS. The therapeutic effects of an engineered human anti-tumour necrosis factor alpha antibody (CDP571) in rheumatoid arthritis. Br J Rheumatol. 1995 Apr;34(4):334–342. [PubMed]
  • Stallmach T, Hebisch G, Joller-Jemelka HI, Orban P, Schwaller J, Engelmann M. Cytokine production and visualized effects in the feto-maternal unit. Quantitative and topographic data on cytokines during intrauterine disease. Lab Invest. 1995 Sep;73(3):384–392. [PubMed]
  • Bermas BL, Petri M, Goldman D, Mittleman B, Miller MW, Stocks NI, Via CS, Shearer GM. T helper cell dysfunction in systemic lupus erythematosus (SLE): relation to disease activity. J Clin Immunol. 1994 May;14(3):169–177. [PubMed]
  • Rich KC, Siegel JN, Jennings C, Rydman RJ, Landay AL. CD4+ lymphocytes in perinatal human immunodeficiency virus (HIV) infection: evidence for pregnancy-induced immune depression in uninfected and HIV-infected women. J Infect Dis. 1995 Nov;172(5):1221–1227. [PubMed]
  • Cherwinski HM, Schumacher JH, Brown KD, Mosmann TR. Two types of mouse helper T cell clone. III. Further differences in lymphokine synthesis between Th1 and Th2 clones revealed by RNA hybridization, functionally monospecific bioassays, and monoclonal antibodies. J Exp Med. 1987 Nov 1;166(5):1229–1244. [PMC free article] [PubMed]
  • Kurt-Jones EA, Hamberg S, Ohara J, Paul WE, Abbas AK. Heterogeneity of helper/inducer T lymphocytes. I. Lymphokine production and lymphokine responsiveness. J Exp Med. 1987 Dec 1;166(6):1774–1787. [PMC free article] [PubMed]
  • Mosmann TR, Coffman RL. TH1 and TH2 cells: different patterns of lymphokine secretion lead to different functional properties. Annu Rev Immunol. 1989;7:145–173. [PubMed]
  • Wegmann TG, Lin H, Guilbert L, Mosmann TR. Bidirectional cytokine interactions in the maternal-fetal relationship: is successful pregnancy a TH2 phenomenon? Immunol Today. 1993 Jul;14(7):353–356. [PubMed]
  • Hill JA, Polgar K, Anderson DJ. T-helper 1-type immunity to trophoblast in women with recurrent spontaneous abortion. JAMA. 1995 Jun 28;273(24):1933–1936. [PubMed]
  • Muluk SC, Clerici M, Via CS, Weir MR, Kimmel PL, Shearer GM. Correlation of in vitro CD4+ T helper cell function with clinical graft status in immunosuppressed kidney transplant recipients. Transplantation. 1991 Aug;52(2):284–291. [PubMed]
  • Schulick RD, Muluk SC, Clerici M, Bermas BL, Via CS, Weir MR, Shearer GM. Value of in vitro CD4+ T helper cell function test for predicting long-term loss of human renal allografts. Transplantation. 1994 Feb;57(3):480–482. [PubMed]
  • Cowchock FS, Smith JB. Fertility among women with recurrent spontaneous abortions--the effect of paternal cell immunization treatment. Am J Reprod Immunol. 1995 Feb;33(2):176–181. [PubMed]
  • Hill JA. Immunological mechanisms of pregnancy maintenance and failure: a critique of theories and therapy. Am J Reprod Immunol. 1990 Jan-Feb;22(1-2):33–41. [PubMed]
  • Clerici M, Stocks NI, Zajac RA, Boswell RN, Bernstein DC, Mann DL, Shearer GM, Berzofsky JA. Interleukin-2 production used to detect antigenic peptide recognition by T-helper lymphocytes from asymptomatic HIV-seropositive individuals. Nature. 1989 Jun 1;339(6223):383–385. [PubMed]
  • Marzi M, Vigano A, Trabattoni D, Villa ML, Salvaggio A, Clerici E, Clerici M. Characterization of type 1 and type 2 cytokine production profile in physiologic and pathologic human pregnancy. Clin Exp Immunol. 1996 Oct;106(1):127–133. [PubMed]
  • Hill JA, Polgar K, Harlow BL, Anderson DJ. Evidence of embryo- and trophoblast-toxic cellular immune response(s) in women with recurrent spontaneous abortion. Am J Obstet Gynecol. 1992 Apr;166(4):1044–1052. [PubMed]
  • Ecker JL, Laufer MR, Hill JA. Measurement of embryotoxic factors is predictive of pregnancy outcome in women with a history of recurrent abortion. Obstet Gynecol. 1993 Jan;81(1):84–87. [PubMed]

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