Molecular screening of transitional B cells as a prognostic marker of improved graft outcome and reduced rejection risk in kidney transplant

Front Immunol. 2024 Aug 12:15:1433832. doi: 10.3389/fimmu.2024.1433832. eCollection 2024.

Abstract

Introduction: Understanding immune cell dynamics in kidney transplantation may provide insight into the mechanisms of rejection and improve patient management. B cells have gained interest with a special relevance of the "regulatory" subsets and their graft outcome prognostic value. In this study, we aimed to prove that the direct immunophenotyping and target gene expression analysis of kidney transplant patients' fresh whole blood will help to identify graft rejection risk and assist in the monitoring of kidney transplanted patients.

Methods: We employed flow cytometry and qPCR techniques to characterize B and T cell subsets within fresh whole blood samples, with particular emphasis on transitional B cells (TrB) identified as CD19+CD24hiCD38hi. TrB are a relevant population in the context of kidney transplantation and are closely associated with regulatory B cells (Bregs) in humans. Patients were monitored, tracking pertinent clinical parameters and kidney-related events, including alterations in graft function and episodes of biopsy proven rejection.

Results: Higher percentages of TrB cells at 3 months after transplantation were positively associated with better graft outcomes and lower biopsy-proven acute rejection risk. Furthermore, a novel panel of B cell regulatory associated genes was validated at 3 months post-transplantation by qPCR analysis of peripheral blood mononuclear cell (PBMC) mRNA, showing high predictive power of graft events and prognostic value.

Discussion: These findings suggest that monitoring TrB may provide interesting patient management information, improve transplant outcomes, and allow for personalized drug regimens to minimize clinical complications.

Keywords: Breg; acute graft rejection; flow cytometry; immunophenotyping; transitional B cells.

MeSH terms

  • Adult
  • Aged
  • B-Lymphocytes, Regulatory / immunology
  • Biomarkers
  • Female
  • Graft Rejection* / diagnosis
  • Graft Rejection* / immunology
  • Graft Survival / immunology
  • Humans
  • Immunophenotyping
  • Kidney Transplantation* / adverse effects
  • Male
  • Middle Aged
  • Prognosis
  • Treatment Outcome

Substances

  • Biomarkers

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported in part by Instituto Carlos III project PI17/00335, integrated in the National R + D + I, and funded by the ISCIII and the European Regional Development Fund. SG is supported by the Catalan Health department (“Departament de Salut”) in receipt of a grant from PERIS-PIF-Salut (SLT017/20/000158). MC-S is supported by a grant from ISCIII (FI20/00021); FB is a senior researcher from Germans Trias i Pujol Health Science Research Institute, supported by the Health Department of the Catalan Government (Generalitat de Catalunya), and MF is supported by ISCIII (MS19/00018), co-funded by ERDF/ESF, “Investing in your future”. The REMAR group is recognized as a consolidated research group by Agaur (SGR-GRC-00187) and is part of the Spanish network RICORS-2040 funded by the ISCIII and the European Regional Development Funds.