Maternal–Foetal Diabetes Modifies Neonatal Fc Receptor Expression on Human Leucocytes

Abstract

This study investigated the expression of the neonatal Fc receptor (FcRn) in maternal blood, cord blood and placental cells and determined IgG levels in maternal blood and cord blood from diabetic mothers. Peripheral blood, cord blood and placenta samples were collected from 26 mothers with normoglycaemia (non-diabetic, ND group) and 52 with hyperglycaemia (26 with mild gestational hyperglycaemia, MGH group, and 26 with type 2 diabetes mellitus, DM-2 group). Cells expressing CD19 + and FcRn were identified by flow cytometry. Total IgG and its subclasses were quantified by ELISA. Maternal blood from DM-2 and cord blood from MGH exhibited a higher proportion of CD19 + expression by B cells. DM-2 showed a lower proportion of CD19 + cells in placenta. FcRn expression increased in cells from cord blood and placenta from MGH. Maternal blood, cord blood and placenta cells from DM-2 showed lower FcRn expression. Blood IgG levels were lower in DM-2, and cord blood IgG levels were higher in MGH. The highest levels of IgG4 were detected in the blood of hyperglycaemic mothers. The highest IgG3 and IgG4 levels in cord blood were detected in MGH, and the lowest IgG2 and IgG3 levels in DM-2. Maternal hyperglycaemia compromised placental transfer of IgG1, IgG3 and IgG4. The results suggest that regardless of hyperglycaemia degree, it decreases FcRn expression in placenta and blood cells and compromises the production and transfer of antibodies from maternal blood to newborns.

Factors Affecting the FcRn-Mediated Transplacental Transfer of Antibodies and Implications for Vaccination in Pregnancy

“…Stach et al ( 98 ) demonstrated an increased rate of IgG transfer in hyperglycemic mothers for all antigens they studied (GBS, Klebsiella LPS, and Pseudomonas LPS), as did França et al ( 114 ). More recently, De Souza et al investigated both the transfer of IgG and expression of FcRn expression (measured by flow cytometry), in normo- and hyperglycemic mothers ( 115 ). They found that mothers with pre-existing type 2 diabetes had lower total levels of IgG, and reduced leukocyte FcRn expression across maternal blood, cord blood, and placental samples (collected at delivery) compared with normoglycemic mothers.…”

Update on Transplacental Transfer of IgG Subclasses: Impact of Maternal and Fetal Factors

“…These usually reference one review (12) that has a graph illustrating data from a single study (13). We have identified 17 papers that have measured maternal and cord levels of the four IgG subclasses (13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29) (Figure 1). Calculating the mean from these papers produces transfer ratios of 1.36 for IgG1, 0.97 for IgG2, 1.12 for IgG3, and 1.12 for IgG4, although the high inter-study variation in both transfer ratios and the transfer hierarchy of the subclasses makes this average an oversimplification.…”

Gestational Diabetes Mellitus Changes Human Colostrum Immune Composition

“…The immune composition of breast milk changes in the presence of GDM, a disease recognized as a global pandemic characterized not only by increased insulin resistance and glucose intolerance but also by a state of low-grade systemic inflammation and dysregulation of the immune system ( 12 , 35 ), which induces an imbalance between Th1 and Th2 cells favoring inflammatory responses. Furthermore, due to changes in glucose metabolism, the components of milk that these women produce are also altered ( 16 ).…”

“…In addition, the colostrum has high levels of immunoglobulins, cytokines, and immune cells compared to mature milk ( 9 , 10 ). Furthermore, the colostrum can protect the infant from allergic and chronic diseases and protect the infant from hypertension, type 2 diabetes, and excess weight ( 11 , 12 ).…”