Maternal, Decidual, and Neonatal Lymphocyte Composition Is Affected in Pregnant Kidney Transplant Recipients

Abstract

Pregnancy after renal transplantation is associated with an increased risk of complications. While a delicately balanced uterine immune system is essential for a successful pregnancy, little is known about the uterine immune environment of pregnant kidney transplant recipients. Moreover, children born to kidney transplant recipients are exposed in utero to immunosuppressive drugs, with possible consequences for neonatal outcomes. Here, we defined the effects of kidney transplantation on the immune cell composition during pregnancy with a cohort of kidney transplant recipients as well as healthy controls with uncomplicated pregnancies. Maternal immune cells from peripheral blood were collected during pregnancy as well as from decidua and cord blood obtained after delivery. Multiparameter flow cytometry was used to identify and characterize populations of cells. While systemic immune cell frequencies were altered in kidney transplant patients, immune cell dynamics over the course of pregnancy were largely similar to healthy women. In the decidua of women with a kidney transplant, we observed a decreased frequency of HLA-DR+ Treg, particularly in those treated with tacrolimus versus those that were treated with azathioprine next to tacrolimus, or with azathioprine alone. In addition, both the innate and adaptive neonatal immune system of children born to kidney transplant recipients was significantly altered compared to neonates born from uncomplicated pregnancies. Overall, our findings indicate a significant and distinct impact on the maternal systemic, uterine, and neonatal immune cell composition in pregnant kidney transplant recipients, which could have important consequences for the incidence of pregnancy complications, treatment decisions, and the offspring’s health.

Risk factors associated with adverse pregnancy outcomes and postpartum exacerbation in women with myasthenia gravis

“…TAC is compatible with pregnancy and lactation according to the European League Against Rheumatism, 35 and also purposed utility in MG pregnant women by practice guidelines in some countries 36,37 . On the other hand, recent research found a strong decrease in uterine HLA‐DR+ Treg and maternal blood Treg in women who received TAC 38 . It has been demonstrated that an impairment in Treg number and function can result in the loss of immune tolerance, and thus the emergence of an uncontrolled autoimmune response.…”

“…36,37 On the other hand, recent research found a strong decrease in uterine HLA-DR+ Treg and maternal blood Treg in women who received TAC. 38 It has been demonstrated that an impairment in Treg number and function can result in the loss of immune tolerance, and thus the emergence of an uncontrolled autoimmune response. Hence, pregnant women should be informed about both the fetal risks when continuing therapy and the possibility of MG worsening after drug withdrawal.…”

The Effect of In Utero Exposure to Maternal Inflammatory Bowel Disease and Immunomodulators on Infant Immune System Development and Function

“… 129 CD45RA+RO- naïve T cells increased in cyclosporin-exposed children CD45RA-RO+ memory T cells more numerous in azathioprine-exposed children. 126 , 127 , 130 , 131 CD25 expression on T cells and CD5 expression on B cells fails to increment over time. 127 Decreased Treg numbers at birth.…”

“…However, the ability to draw firm conclusions from these reports is limited by the small number of infants (<15 participants in each study). 126 , 127 , 130 , 131 , 149 …”