Wang Z C, Yunis E J, De los Santos M J, Xiao L, Anderson D J, Hill J A
Fearing Laboratory, Department of Obstetrics, Gynecology and Reproductive Biology, Brigham and Women's Hospital, Boston, MA 02115, USA.
Genes Immun. 2002 Feb;3(1):38-42. doi: 10.1038/sj.gene.6363812.
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-1beta 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-gamma production of peripheral blood mononuclear cells (PBMCs) stimulated with a trophoblast cell-line extract. Significantly higher IFN-gamma 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.
复发性流产（RPL）是妊娠早期的一种常见病症。最近的证据表明，辅助性T细胞1（Th1）型免疫与妊娠失败有关，尤其是在病因不明的复发性流产女性中，而Th2型免疫与妊娠成功有关。白细胞介素（IL）-1可能影响Th1/Th2免疫反应性，并与成功妊娠的建立有关。在本研究中，我们调查了有复发性流产病史女性的IL-1β基因（IL1B）多态性。在有复发性流产病史的女性中，发现IL1B启动子区域变体IL1-511C和IL1B-31T的频率显著增加。仅在通过滋养层细胞系提取物刺激外周血单个核细胞（PBMC）产生干扰素-γ确定有针对滋养层的Th1免疫证据的病例中，发现这两种变体及其纯合子的频率增加。复发性流产女性中，PBMC对滋养层反应产生的干扰素-γ显著升高与变体IL1B-511C及其纯合性相关。这些结果表明，IL1B启动子区域的-511C和-31T变体赋予了与针对滋养层抗原的Th1免疫相关的复发性流产风险。
