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Pediatr Nephrol. 2016 Jun;31(6):1001-10. doi: 10.1007/s00467-015-3274-4. Epub 2015 Dec 21.

Cellular immune profile of kidney transplant patients developing anti-HLA antibodies during childhood.

Author information

1
University Department of Pediatrics, DPUO, Unit of Immune and Infectious Diseases, Bambino Gesù Children's Hospital and Research Institute (IRCCS), Piazza S. Onofrio 4, 00165, Rome, Italy. veronica.santilli@hotmail.it.
2
University Department of Pediatrics, DPUO, Unit of Immune and Infectious Diseases, Bambino Gesù Children's Hospital and Research Institute (IRCCS), Piazza S. Onofrio 4, 00165, Rome, Italy.
3
Nephrology and Urology Department, Bambino Gesù Children's Hospital and Research Institute (IRCCS), Piazza S. Onofrio 4, 00165, Rome, Italy.
4
Chair of Pediatrics, Department of Public Health, University of Rome Tor Vergata, Via Montpellier 1, 00133, Rome, Italy.
5
National Council of Researches IFT Unit of Rome S. Camillo Hospital - Regional Transplant Center Lazio, S. Camillo Hospital, C.ne Gianicolense 87, 00152, Rome, Italy.

Abstract

BACKGROUND:

In the field of kidney transplantation, identifying early signatures of humoral rejection is a key challenge.

METHODS:

We investigated the presence of anti-HLA antibodies and the distribution of lymphocyte subpopulations in 77 kidney-transplanted children and young adults compared to 23 healthy controls. Moreover, we tested whether the presence of anti-HLA antibodies could be related to modification in lymphocyte phenotype. Finally, we correlated the presence of anti-HLA antibodies and specific alteration of lymphocyte subsets with clinical outcomes.

RESULTS:

In kidney-transplanted children who developed anti-HLA antibodies, we observed an expansion of double-negative B cells (CD19 + CD27-IgD-), indicating premature aging of this compartment. Moreover, we reported signs of impaired B cell regulation, indicated by a higher IL-21R+ B cell frequency associated with an abnormal increase of follicular helper T cells. Finally, a considerable reduction in CD8+ effector T and invariant Natural killer T (NKT) cells was observed. The stability of graft function over time is significantly correlated with the frequency of peripheral effector CD4+ and CD8+ T cells and invariant NKT cells.

CONCLUSIONS:

This study supports the usefulness of lymphocyte subset as one of a spectrum of early diagnostic tools required to identify patients at risk of developing donor alloimmune response.

KEYWORDS:

Humoral allograft rejection; Kidney transplantation; Lymphocyte subpopulations; Predictive biomarkers

PMID:
26692023
DOI:
10.1007/s00467-015-3274-4
[Indexed for MEDLINE]

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