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.
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.
Wang
Z C
ZC
Fearing Laboratory, Department of Obstetrics, Gynecology and Reproductive Biology, Brigham and Women's Hospital, Boston, MA 02115, USA.
Yunis
E J
EJ
De los Santos
M J
MJ
Xiao
L
L
Anderson
D J
DJ
Hill
J A
JA
D000026:Abortion, Habitual / Q000235:genetics* / Q000276:immunology*; D000941:Antigens / Q000276:immunology; D016022:Case-Control Studies; D002478:Cells, Cultured; D005260:Female; D005787:Gene Frequency; D014644:Genetic Variation; D005838:Genotype; D006720:Homozygote; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D007375:Interleukin-1 / Q000235:genetics*; D011110:Polymorphism, Genetic; D011247:Pregnancy; D011401:Promoter Regions, Genetic; D017584:Reproductive History; D012189:Retrospective Studies; D018417:Th1 Cells / Q000276:immunology*; D014327:Trophoblasts / Q000276:immunology*
D000941:Antigens; D007375:Interleukin-1; D007371:Interferon-gamma