C- 06 : Pregnancy and the kidney
H- 12 : Immonosuppressive regimens
Immunophenotypic Profile and Increased Risk of Hospital Admission for
Infection in Infants Born to Female Kidney Transplant Recipients
E. Ono1, A. M. dos Santos, P. O. Viana, M. I. S. Dinelli, N. Sass, L. De Oliveira, A. L. Goulart and M. I.
de Moraes-Pinto
Journal : American Journal of Transplantation
Year : 2015 / Month : June first published online: APR 2015
Volume 15
Pages 1654–1665
DOI: 10.1111/ajt.13143
ABSTRACT
Children born to female kidney recipients are exposed to immunosuppressive drugs during gestation.
Little is known about their immune system at birth or in the long term. Twenty-eight children born to
female kidney recipients and 40 full-term children born to healthy mothers were evaluated. T, B, NK,
NKT, γδT cells were assessed by flow cytometry and functional evaluation of T and dendritic cells after
in vitro activation was performed at birth and at 8 months of age. At birth, infants born to female kidney
recipients showed lower numbers of CD4+ T, NKT and intense reduction of B cells (median cells/mm3,
transplant: 153.7 X control: 512.4; p < 0.001). There was also a reduced percentage of activated CD8+
T and of CD4+ regulatory T cells. Activated memory and exhausted memory B cells showed higher
percentages among children exposed to immunosuppressors when compared to control group. At 8
months, most immune alterations were no longer observed, but four children still had low numbers of
some lymphocyte subsets at this age. Children born to female kidney recipients had 4.351 (95% CI:
1.026–15.225; p = 0.046) higher risk of hospital admission in the first months of life—some, with severe
clinical manifestations—than those born to healthy women.
COMMENTS
This study reports abnormal peripheral lymphocyte counts and an increased incidence of hospital
admission for infections among infants born to mothers with kidney transplantsThis study questions the
effects of in utero exposure to immunosuppressive agents on immune system development and longterm disease risk in this population.
Pregnancy and live birth are increasingly common among female kidney transplant recipients. High
incidences of obstetric complications, such as hypertension, pre-eclampsia and gestational diabetes,
support a high-risk classification of pregnancy in this population. Moreover kidney transplant recipients
tend to deliver babies who are preterm and/or have low birth weights. Little data on the long-term
health of these children are available and the impact of in utero exposure to immunosuppressive
agents on the immune system at birth and during infancy is unclear.
In this prospective study, the authors analysed the immune systems and hospital admissions of 28
children born to kidney transplant recipients and 40 children born to healthy mothers at full-term. They
report that at birth, infants in the transplant group showed lower numbers of peripheral CD4+ T cells,
natural killer T (NKT) cells, activated CD8+ T cells and CD4+ regulatory T cells, a substantial reduction
in B cell numbers, and increased percentages of activated and exhausted memory B cells, compared
with those in the control group. At 8 months of age most of these abnormalities were no longer
observed.
Most importantly, the rate of hospital admission during the first year of life was fourfold higher among
children in the transplant group than among those in the control group. Most of the hospitalizations
were for infections, some of which were clinically severe. The types of infections reported in this study
(that is, pneumonia and sepsis) could be consistent with a humoral immune defect in babies born to
kidney transplant recipients. The possibility also exists that a combination of several immune defects
are necessary to confer an increased infection risk in this population.
These findings suggest a detrimental effect of in utero exposure to immunosuppressive drugs on innate
immune function, which could potentially result in reduced resistance to infections.
During their pregnancy the women received an immunosuppressive regimen consisting of prednisone,
azathioprine and either tacrolimus or ciclosporin. Interestingly, all neonates in the transplant group who
were hospitalized for infections during the study period had been exposed to tacrolimus in utero. They
also tended to have lower B cell numbers at birth than did infants who had been exposed to
ciclosporin.
To conclude this study is the first prospective investigation of the immune profile of infants born to
mothers with kidney transplants with follow-up surveillance and clinical outcomes in the first year of life.
Importantly, the researchers report an increased risk of severe infections requiring hospitalization
among these infants compared with those born to healthy women. These findings emphasize the
necessity of close monitoring of the immune system in children who might be at risk of adverse
outcomes as a result of in utero exposure to immunosuppressive agents.
Pr. Jacques CHANARD
Professor of Nephrology