Impaired immunosuppressive activities of glycodelin-A in pregnant women with gestational diabetes mellitus

Abstract

Gestational Diabetes Mellitus (GDM) is defined as glucose intolerance of various degrees that is first detected during pregnancy and disappeared after pregnancy. It is the most common metabolic disorder of pregnancy, occurring in up to 13% and 7% of the pregnancies in the local and United States population, respectively. Women who developed GDM had experienced abnormally high fetal mortality and other risk such as spontaneous abortion and placental alternation. The abnormal carbohydrate metabolism may contribute to the pathology of diabetic complications. Glycodelin-A (GdA) is a glycoprotein belonging to the lipocalin family with contraceptive, immunosuppressive and morphogenic properties. GdA is well accepted to be involved in feto-maternal defense as it is abundant in the decidua and modulate the activities of T cell, B cell and NK cell. Since the glycosylation of GdA is essential for its immunosuppressive activities, we hypothesis that gestational diabetic pregnancy may alters the glycosylation of GdA, and thereby leading to defective immunosuppression. In this study, GdA in amniotic fluid from women having normal glucose tolerance (N.GdA) or GDM (D.GdA) were purified with our established protocol. Our results showed that N.GdA and D.GdA shared the same protein core but with different glycosylation as demonstrated by their differential lectin binding patterns. In addition, D.GdA has lower ability in suppressing the proliferation of Jurkat cells and peripheral blood mononuclear cells (PBMCs) as compared to N.GdA. This reduced inhibitory effect on lymphocytes by D.GdA was associated with impaired ability to induce cell death and to inhibit IL-2 secretion. Taken together, our data suggest that the immunosuppressive activities of D.GdA on lymphocytes were impaired as compared to N.GdA due to change in glycosylation. Further investigation of the type and quantity of a particular GdA-derived glycan which affecting its biological activity will enhance our understanding of the cause of pregnancy loss in diabetic mother, and provide the basis for the development of new treatment strategies.