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Alterations in Antibody Subclass Immune Reactivity to Trophoblast-derived Fetal Fibronectin and α2-Macroglobulin in Women with Recurrent Pregnancy Loss



Rhiana D. Saunders, MD, Department of Obstetrics and Gynecology, Madigan Army Medical Center, 9040 Fitzsimmons Drive, Tacoma, WA 98431, USA. E-mail: or



Increasing evidence supports the involvement of complex antibody-mediated immunologic events at the decidua–trophoblast interface. Our objective is to define the humoral immune responses of pregnant women with a history of recurrent pregnancy loss (RPL) compared with gestation-age-matched and non-pregnant controls in terms of trophoblast-derived antigenic targets and IgG subclasses.

Method of study

Immunoprecipitation and Western immunoblotting were performed to characterize IgG subclass reactivity to Sw.71 trophoblast–derived fetal fibronectin and alpha-2-macroglobulin, using serum obtained from first-trimester pregnant RPL subjects, gestation-age-matched controls, and non-pregnant controls.


Using a generalized linear model, sera from women with a history of RPL exhibited increased IgG3 immunoreactivity to trophoblast-derived fetal fibronectin and alpha-2-macroglobulin compared with controls (< 0.001 and < 0.001, respectively).


IgG3 reactivity in women with RPL may play a significant role in aberrant immune-regulatory mechanisms in early pregnancy. Further investigations into the role of autoantibodies against trophoblast-derived proteins in implantation and pregnancy are warranted.