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T helper 1-type immunity to trophoblast antigens in women with a history of recurrent pregnancy loss is associated with polymorphism of the IL1B promoter region

Abstract

Recurrent pregnancy loss (RPL) is a common disorder during early gestation. Recent evidence suggests that T helper 1 (Th1)-type immunity is associated with unsuccessful pregnancy especially in women with RPL of otherwise unknown etiology, while Th2-type immunity is associated with pregnancy success. Interleukin (IL)-1 may influence Th1/Th2 immune responsiveness and has been implicated in the establishment of successful pregnancy. In the present study, we investigated polymorphism of the IL-1β gene (IL1B) in women with a history of RPL. Significant increases in the frequencies of IL1B promoter region variants IL1-511C and IL1B-31T were found in women with a history of RPL. Increased frequencies of these two variants and their homozygotes were found only in cases having evidence of Th1 immunity to trophoblast as determined by IFN-γ production of peripheral blood mononuclear cells (PBMCs) stimulated with a trophoblast cell-line extract. Significantly higher IFN-γ production by PBMCs in response to trophoblast correlated with variant IL1B-511C and its homozygocity in women with RPL. These results suggest that variants −511C and −31T in the IL1B promoter region confer risk for RPL associated with Th1 immunity to trophoblast antigens.

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Acknowledgements

We thank Dr Joseph Politch for his excellent statistical assistance and Dr Raina Fichorova for her valuable suggestions.

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Correspondence to J A Hill.

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This work was supported by the Fearing Laboratory Endowment and grant HL29583 (EJY) from the NIH.

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Wang, Z., Yunis, E., De los Santos, M. et al. T helper 1-type immunity to trophoblast antigens in women with a history of recurrent pregnancy loss is associated with polymorphism of the IL1B promoter region. Genes Immun 3, 38–42 (2002). https://doi.org/10.1038/sj.gene.6363812

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