Co-stimulatory molecules, microRNAs, and modulation of the maternal-fetal immune response in gestational Diabetes Mellitus

Abstract

Gestational Diabetes Mellitus (GDM) is an increasingly prevalent endocrine pathology associated with obstetric and perinatal complications. The development of mild inflammatory reaction and insulin resistance (IR) are part of the physiological adaptive phenomena of normal gestations and, in patients with GDM, these two processes are exacerbated. These alterations seem to be related to the hyperactivation of T lymphocytes and the compromise of mechanisms of immunological tolerance. Among the several factors involved in this process, the participation of costimulatory molecules, CTLA-4 and CD28, is highlighted. In a previous study, we observed an imbalance in the expression of these receptors in circulating T lymphocytes of diabetic pregnant women. Other investigators have shown higher levels of these molecules in soluble form in autoimmune diseases and obstetric pathologies. It is also known that microRNAs (miRs) are involved in the regulation of various cellular processes, including the control of metabolic mechanisms and activation of T lymphocytes. The identification of miR is a tool that has been progressively used for diagnosis, monitoring and targeting therapeutic. Some miRs have been associated with hyperglycemia in general, and others specifically with GDM. Considering these observations, our objectives are to characterize the expression pattern of costimulatory molecules in maternal and fetal blood lymphocytes and of the decidua of pregnant women with GDM; evaluate the serum levels of these molecules; to analyze the plasmatic miRNA profile related to the immune response and to validate their participation in these cases. We believe that this study may contribute to the knowledge of the pathophysiology of DMG and, thus, may provide the best approach for diabetic pregnant women. (AU)