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

Veronica Santilli, Alberto Cagigi, Isabella Guzzo, Stefano Rinaldi, Nadia Mora, Federica Zotta, Antonina Piazza, Paolo Rossi, Francesco Emma, Luca Dello Strologo, Paolo Palma

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)1001-10
Number of pages10
JournalPediatric Nephrology
Volume31
Issue number6
DOIs
Publication statusPublished - Jun 2016

Keywords

  • Adolescent
  • Adult
  • Antilymphocyte Serum
  • B-Lymphocytes
  • CD8-Positive T-Lymphocytes
  • Child
  • Child, Preschool
  • Female
  • Flow Cytometry
  • Graft Rejection
  • HLA Antigens
  • Humans
  • Immunity, Cellular
  • Kidney Transplantation
  • Lymphocyte Subsets
  • Male
  • Natural Killer T-Cells
  • T-Lymphocytes, Helper-Inducer
  • Young Adult
  • Journal Article
  • Research Support, Non-U.S. Gov't

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