B-cell-related biomarkers of tolerance are up-regulated in rejection-free kidney transplant recipients

Transplantation. 2013 Jan 15;95(1):148-54. doi: 10.1097/TP.0b013e3182789a24.

Abstract

Background: Molecular signatures have recently been identified in operationally tolerant long-term kidney transplant patients; however, their expression in patients on immunosuppression remains unclear.

Methods: In this prospective study, the gene expression profiles of eight selected tolerance-associated genes (MS4A1, CD79B, TCL1A, TMEM176B, FOXP3, TOAG-1, MAN1A1, and TLR5) in the peripheral blood of 67 kidney transplant recipients at days 0, 7, 14, 21, 28, 60, 90, and at 6 and 12 months, and in graft biopsies were measured. Similarly, using flow cytometry, CD45CD19CD3 B-cell counts were evaluated in the follow-up. Expression patterns were compared among patients with biopsy-proven acute rejection, borderline changes, and in rejection-free patients. A generalized linear mixed model with gamma distribution for repeated measures adjusted for induction therapy was used for statistical analysis of longitudinal data and Kruskal-Wallis test for case biopsy data.

Results: Compared to patients with rejection, a significantly higher number of peripheral B cells were observed during follow-up in rejection-free patients and in patients with borderline changes. Gene expression patterns of MS4A1 (CD20), TCL1A, CD79B, TOAG-1, and FOXP3 genes were significantly higher in rejection-free patients as compared to rejection group with the highest differences during the first 3 months. In contrast, TMEM176B (TORID) was up-regulated in the rejection group. Similar trends were also observed between patients with borderline changes and acute rejection. Higher intragraft expression of TOAG-1 was observed in rejection-free patients.

Conclusions: These observations suggest an association of B-cell signatures, seen also in drug-free tolerant patients, with controlled alloimmune response.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • B-Lymphocytes / immunology*
  • Biomarkers
  • Female
  • Forkhead Transcription Factors / analysis
  • Gene Expression Profiling
  • Graft Rejection*
  • Humans
  • Immune Tolerance*
  • Kidney Transplantation / immunology*
  • Male
  • Middle Aged
  • Prospective Studies
  • Proto-Oncogene Proteins / genetics
  • Up-Regulation

Substances

  • Biomarkers
  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • Proto-Oncogene Proteins
  • TCL1A protein, human