Clinicopathological and immunohistochemical analysis of plasma cell-rich rejection in renal transplantation: Involvement of intratubular Th1/Th2 balance in plasma cell enrichment

Nephrology (Carlton). 2018 Jul:23 Suppl 2:52-57. doi: 10.1111/nep.13273.

Abstract

Aim: Plasma cell-rich rejection (PCRR) has been considered a subtype of acute T-cell-mediated rejection (ATCR). However, PCRR is recognized as refractory rejection and different from ATCR in various ways. In order to elucidate the pathogenesis of PCRR, we analysed PCRR clinicopathologically and immunohistochemically by comparing it with ATCR.

Methods: Twelve cases of PCRR (PCRRs) and 22 cases of usual ATCR (ATCRs) diagnosed at our hospital between January 2008 and March 2017 were included. Between PCRRs and ATCRs, we compared clinical data, Banff classification, graft outcome and the total sum number of T-bet- and GATA3-positive lymphocytes infiltrating in tubular epithelium using immunohistochemistry.

Results: Plasma cell-rich rejections occurred later than ATCRs (median time after transplantation 1340.5 days vs. 52.5 days). Serum creatinine levels at discharge after treatment were significantly higher in PCRRs than in ATCRs (median 2.38 vs. 1.65 mg/dL). Cumulative rate of graft loss was significantly higher in PCRRs than in ATCRs (1-, 2- and 5-year: 26.7%, 51.1% and 51.1% vs. 0%, 0% and 17.5%). For profiles of Th1 and Th2, we found significantly lower ratio of T-bet/GATA3-positive lymphocytes in PCRRs compared with ATCRs.

Conclusion: This study suggests that PCRR is more refractory than ATCR and there are significant differences in populations of helper T-cell subsets between them. We consider helper T-cell subset analysis valuable for developing new treatment strategies for PCRR.

Keywords: acute T-cell-mediated rejection; helper T-cell subset; plasma cell-rich rejection; renal transplantation; transcription factor.

Publication types

  • Comparative Study

MeSH terms

  • Acute Disease
  • Adolescent
  • Adult
  • Aged
  • Biopsy
  • Child
  • Female
  • GATA3 Transcription Factor / analysis
  • Graft Rejection / immunology*
  • Graft Rejection / metabolism
  • Graft Rejection / pathology
  • Humans
  • Immunity, Cellular*
  • Immunohistochemistry*
  • Kidney / chemistry
  • Kidney / immunology*
  • Kidney / pathology
  • Kidney Transplantation / adverse effects*
  • Male
  • Middle Aged
  • Plasma Cells / chemistry
  • Plasma Cells / immunology*
  • Plasma Cells / pathology
  • Predictive Value of Tests
  • Retrospective Studies
  • T-Box Domain Proteins / analysis
  • Th1 Cells / chemistry
  • Th1 Cells / immunology*
  • Th1 Cells / pathology
  • Th2 Cells / chemistry
  • Th2 Cells / immunology*
  • Th2 Cells / pathology
  • Treatment Outcome
  • Young Adult

Substances

  • GATA3 Transcription Factor
  • GATA3 protein, human
  • T-Box Domain Proteins
  • T-box transcription factor TBX21