Saturday, August 21, 2010

Preeclampsia is associated with increased cytotoxic T-cell capacity to paternal antigens.

Am J Obstet Gynecol. 2010 Aug 17. [Epub ahead of print]

Preeclampsia is associated with increased cytotoxic T-cell capacity to paternal antigens.
de Groot CJ, van der Mast BJ, Visser W, De Kuiper P, Weimar W, Van Besouw NM.

Department of Obstetrics and Gynecology, Erasmus University Medical Center, Rotterdam, The Netherlands; Department of Obstetrics and Gynecology, Medical Center Haaglanden, The Hague, The Netherlands.

Abstract
OBJECTIVE: During an uncomplicated pregnancy the conceptus is a semiallogeneic entity in which rejection is prevented by suppression of the maternal immune system. We hypothesized that this suppression is disturbed in patients with preeclampsia and that a maternal immune response to fetal (foreign/paternal) antigens in the fetal-maternal interface may be responsible for local inflammation, with subsequent endothelial dysfunction and systemic disease.

STUDY DESIGN: Blood samples were obtained from 14 women with preeclampsia (cases), 14 gestational-age and parity-matched women with uncomplicated pregnancies (controls), and their partners. We determined the partner-specific cytotoxic T-lymphocyte precursor frequency (CTLpf) and the CTLpf directed to unrelated partners with uncomplicated pregnancies. We measured the CTLpf in peripheral blood mononuclear cells (PBMCs) from cases and controls using limited-dilution assays. In addition, proliferation was tested in a mixed-lymphocyte culture (MLR).

RESULTS: The partner-specific CTLpf was significantly higher in cases compared with controls (median, 183 [15-338] vs 67 [9-232] per million PBMCs, P = .02). In contrast, in women with uncomplicated pregnancies, the partner-specific CTLpf was down-regulated compared with the CTLpf directed to an unrelated partner who fathered uncomplicated pregnancies (P = .02). No difference was found in partner-specific MLR response between cases and controls.

CONCLUSION: These results suggest that women with preeclampsia have a higher cytotoxic T-cell response to paternal antigens compared with pregnant controls. This insufficiently suppressed immune response may eventually lead to the development of preeclampsia.

PMID: 20723874 [PubMed - as supplied by publisher]

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