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

Dorien Feyaerts,Gaia Comitini,Renate G Van Der Molen,Mariam M S Baghdady,Irma Joosten,Bram Van Cranenbroek,Henk W Van Hamersvelt,Olivier W H Van Der Heijden,Joshua Gillard,Lina Rigodanzo Marins,A Titia Lely

doi:10.3389/fimmu.2021.735564

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.

Highlights

Achieving successful pregnancy in women with advanced chronic kidney disease or end-stage renal disease is clinically challenging [1, 2]
We show for the first time that the uterine HLA-DR+ regulatory T cell frequencies are affected in women with a kidney transplant, in those treated with tacrolimus
While we did not observe a difference in CD25+CD127low FOXP3+ Treg frequency (Figure 1B), we did observe a significant decrease in the percentage of HLA-DR+ Treg within the total uterine Treg pool of kidney transplant recipients compared to healthy individuals (Figure 1C)

Summary

Introduction

Achieving successful pregnancy in women with advanced chronic kidney disease or end-stage renal disease is clinically challenging [1, 2]. The number of pregnancies in patients with a kidney transplant is rising [6]. Kidney transplant recipients have a higher risk of developing pregnancy complications [5]. Low birth weight children (< 2500 g; 50%) and preterm delivery (< 37 weeks of gestation; 50%) is more common in kidney transplant recipients compared to the general population [5, 6, 8] These adverse pregnancy outcomes may be a result of impaired (pre-pregnancy) graft function, pre-pregnancy hypertension, or the effect of immunosuppression [5, 9,10,11]. Immune perturbations associated with pregnancy complications are well-documented and may offer an explanation to the higher incidence of complications observed in kidney transplant recipients [16,17,18,19]

Methods

Results

Conclusion