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Cell-mediated immunity to trophoblast antigens in women with recurrent spontaneous abortion
1Recurrent Miscarriage Center, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
Objectives:
The purpose of this study was to determine whether trophoblast antigens activate cell-mediated immune responses in women with recurrent abortion of unknown cause by inducing lymphocyte proliferation and to correlate this with embryotoxic factor production.
Study Design:
Mononuclear cells were isolated from 57 nonpregnant women with recurrent abortion of unknown cause and from 10 fertile controls with normal reproductive histories. Lymphocyte proliferation assays were performed with trophoblast antigen extracts from the human choriocarcinoma cell lines Jeg-3 and JAR, fractionated trophoblast antigens, and for control, red blood cell membrane antigens. A stimulation index > 3 was considered significant stimulation. Trophoblast-stimulated culture supernatants were also tested for embryotoxic activity.
Results:
Thirty (52.6%) women with recurrent abortion of unknown cause responded to trophoblast antigen stimulation with a stimulation index > 3, whereas none of the control group responded. Neither patients with recurrent abortion nor women with normal reproductive histories responded to red blood cell membrane antigen. The mean stimulation index in the trophoblast antigen lymphocyte proliferation assay was significantly higher in women with recurrent abortion than in women with normal reproductive histories (3.99 +/- 2.82 vs 1.64 +/- 0.34, p < 0.01). Antigen extracts from the cytosol and membrane fractions of Jeg-3 provided the strongest stimulation. Lymphocyte proliferation correlated with embryotoxic factor production; 90.0% of women with a stimulation index > 3 and none of the controls produced embryotoxic factors after stimulation with trophoblast antigens.
Conclusion:
In this study 52.6% of women with recurrent abortion of unknown cause compared with none in controls exhibited in vitro evidence of T-cell immunity to trophoblast antigen stimulation. Further work is needed to determine whether T-cell immunity to trophoblast is involved in the pathogenesis of recurrent spontaneous abortion.