Status of peripheral blood natural killer cells in women with recurrent spontaneous abortions and infertility of unknown aetiology.

The aim of this study was to investigate the functional status and immunophenotypic characteristics of natural killer (NK) cells in women who suffer recurrent spontaneous abortions (RSA) or have infertility of unknown aetiology. Peripheral blood mononuclear cells (PBMC) were obtained from 40 study patients and 13 normal healthy multiparous controls. NK cells were identified using anti-CD56 and anti-CD16 monoclonal antibodies (mAb). The expression of CD69, CD25, CD122, CD30, CD154, CD128 and CD94 on NK cells was detected using specific mAb and analysed by flow cytometry. CD69 expression on NK cells after ED(27) human trophoblast cell line co-culture with PBMC was also investigated. A significant increase in CD69 expression on CD56(+) NK cells was demonstrated in women with RSA (P < 0.005) and infertility (P < 0.05) as compared with that of normal controls. Conversely, CD94 expression was significantly decreased in women with RSA (P < 0.005) and infertility (P < 0.05) in comparison with that of controls. Increased CD69 expression on NK cells was induced after 24 h co-culture with ED(27). In conclusion, peripheral blood NK cells of women with RSA and infertility of unknown aetiology have higher proportions of activated NK cells in vivo. Unbalanced CD69 and CD94 expression may explain the underlying pathology.

Immunopathology of the implantation site utilizing monoclonal antibodies to natural killer cells in women with recurrent pregnancy losses.

PROBLEM: Placental lesions of 71 women with documented recurrent spontaneous abortions of unknown etiology were evaluated using immunohistochemical staining. METHOD OF STUDY: Placental tissue blocks (less than 12 weeks gestation) from prior pregnancy losses were obtained, recut, and analyzed utilizing monoclonal antibody to identify the trophoblast (cytokeratin 8/18) and natural killer (NK) cells (CD57) at the implantation site. The following features were evaluated: trophoblast invasion pattern; syncytium formation; vasculitis and thromboembolism of decidual vessels; decidual inflammation; decidual necrosis; fibrin deposition at the decidual necrosis site; mononuclear-cell infiltration in villi and intervillous space; perivillous fibrin deposition; trophoblast morphology; and quantitation of CD57+ NK cells within the decidual tissue near the implantation site. Controls consisted of 20 healthy women with no history of recurrent pregnancy losses, who had their pregnancies electively terminated. RESULTS: Of the women studied, 29.6% demonstrated elevated CD57+ NK cells at the implantation site (P = 0.030), 54.1% had inadequate cytotrophoblast invasion depth (P = 0.000), 44.1% demonstrated inadequate syncytium formation (P = 0.004), and 33.9% presented thromboembolism in decidual vessels (P = 0.025). CONCLUSION: Some women with recurrent spontaneous abortions demonstrate abnormal placental lesions at the implantation site. Immunopathologic evaluation of the placental implantation site that terminated in a spontaneous abortion may reveal the immunopathogenesis of previous pregnancy losses.