PD-1 and PD-L1 Expression on Circulating Lymphocytes as a Marker of Epstein-Barr Virus Reactivation-Associated Proliferative Glomerulonephritis

Int J Mol Sci. 2020 Oct 27;21(21):8001. doi: 10.3390/ijms21218001.

Abstract

Alterations to the programmed cell death protein-1 (PD-1) pathway were previously shown to be involved in a poorer prognosis for patients with proliferative glomerulonephritis (PGN). Here, we investigated the association between several infectious agents and the expression of PD-1 and its ligand (PD-L1) on T and B lymphocytes in patients with PGN and nonproliferative glomerulonephritis (NPGN). A cohort of 45 newly-diagnosed patients (23 with PGN and 22 with NPGN) and 20 healthy volunteers was enrolled. The percentage of peripheral blood mononuclear cells expressing PD-1 and PD-L1 antigens was determined by flow cytometry. We found PD-1 and PD-L1 expression on T and B lymphocytes was higher in PGN patients than in NPGN patients and controls. We also found that reactivation of the Epstein-Barr virus (EBV) correlated with the expression of PD-1/PD-L1 antigens in patients with PGN. Further receiver operating characteristic analysis indicated that PD-1 expression could distinguish EBV-positive PGN patients from those with NPGN or healthy controls. The use of PD-1 expression as a non-invasive marker of PGN should be further investigated.

Keywords: CD19+ B lymphocyte; CD4+ T lymphocyte; CD8+ T lymphocyte; EBV; Epstein–Barr virus; PD-1; PD-L1; glomerulonephritis; immunology; programmed cell death protein 1; programmed death-ligand 1.

MeSH terms

  • Adult
  • Aged
  • B-Lymphocytes / metabolism*
  • B7-H1 Antigen / metabolism*
  • Case-Control Studies
  • Epstein-Barr Virus Infections / complications*
  • Epstein-Barr Virus Infections / immunology
  • Female
  • Glomerulonephritis / immunology
  • Glomerulonephritis / virology*
  • Humans
  • Leukocytes, Mononuclear / metabolism
  • Male
  • Middle Aged
  • Programmed Cell Death 1 Receptor / metabolism*
  • ROC Curve
  • T-Lymphocytes / metabolism*
  • Up-Regulation
  • Young Adult

Substances

  • B7-H1 Antigen
  • CD274 protein, human
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor