The diagnostic role of PD-1+ CXCR5+ follicular helper CD8+ T cell in renal allograft dysfunction

J Clin Lab Anal. 2022 Feb;36(2):e24200. doi: 10.1002/jcla.24200. Epub 2021 Dec 26.

Abstract

Background: The roles of PD-1+ CXCR5+ follicular helper CD8+ T cell were reported in different disease conditions, but their roles in transplantation are unclear. In this study, the association between PD-1+ CXCR5+ follicular helper CD8+ T cell and renal allograft dysfunction in kidney transplant recipients (KTRs) was investigated.

Methods: 82 KTRs were enrolled in this study. 45 KTRs were included in the chronic allograft dysfunction (CAD) group, and 37 KTRs were included in the stable recipients group. Among the CAD group, 12 cases of antibody-mediated rejection (ABMR) and 4 cases of T cell-mediated rejection (TCMR) were diagnosed by biopsy. The percentage of CXCR5+ CD8+ T cells and the co-expression of signal transducers and activators of transcription 4 (STAT4), STAT5, and PD-1 in peripheral blood were determined by flow cytometry.

Results: The expression of CXCR5 on CD3+ CD8+ T cells and the percentage of STAT5+ CXCR5+ cells in the CD3+ CD8+ T-cell population were significantly lower in the CAD group (p < 0.05), while the expression of PD-1+ CXCR5+ CD8+ T cells was significantly higher (p < 0.05). Through logistic regression analysis, we concluded that the percentage of PD-1+ CXCR5+ CD8+ T cells was an independent risk factor for renal dysfunction. Grouping by pathological type, PD-1+ CXCR5+ CD8+ T cells showed relatively good diagnostic efficacy for ABMR by ROC analysis.

Conclusions: Our results suggested that PD-1+ CXCR5+ CD8+ T cells were a promising biomarker for distinguishing renal allograft dysfunction and different allograft pathological types. Also, our findings may provide new ways of identifying and treating allograft rejection.

Keywords: ABMR; CXCR5+CD8+ T cells; PD-1; chronic renal allograft dysfunction; kidney transplant.

MeSH terms

  • Adult
  • Allografts
  • Biomarkers
  • CD8-Positive T-Lymphocytes / physiology
  • Female
  • Graft Rejection / diagnosis
  • Humans
  • Kidney / physiopathology*
  • Kidney Transplantation*
  • Logistic Models
  • Male
  • Middle Aged
  • Programmed Cell Death 1 Receptor / metabolism*
  • Programmed Cell Death 1 Receptor / physiology
  • ROC Curve
  • Receptors, CXCR5 / metabolism
  • T Follicular Helper Cells / metabolism
  • T Follicular Helper Cells / physiology*

Substances

  • Biomarkers
  • CXCR5 protein, human
  • Programmed Cell Death 1 Receptor
  • Receptors, CXCR5