Immunosuppressive therapies after intestinal transplant modulate the expression of Th1 signature genes during acute cellular rejection. Implications in the search for rejection biomarkers

Clin Transplant. 2014 Dec;28(12):1365-71. doi: 10.1111/ctr.12464. Epub 2014 Nov 26.

Abstract

Background and aims: Acute cellular rejection (ACR) and infections are leading causes of graft loss and death in intestinal transplant patients. Our aim was to evaluate the impact of maintenance immunosuppressive therapies on the expression of pro-inflammatory mediators in small bowel at ACR diagnosis.

Materials and methods: We analyzed expression levels of Th1-associated genes, IFNG, CXCL10, and CXCL11 by qPCR in 46 selected graft biopsies unequivocally assigned to mild ACR (n = 14) or normal histopathology and clinical condition (n = 32) from 15 patients receiving two different immunosuppressive (IS) schemes. Double treatment: corticosteroids and tacrolimus (n = 17) and triple treatment: sirolimus or mycophenolate mofetil in addition to the basal therapy (n = 29).

Results: IFNG, CXCL10, and CXCL11 were induced during rejection (p < 0.05; p < 0.005, and p < 0.05, respectively). However, when rejection and control groups were classified according to immunosuppressive treatment, in the rejection group, significant differences of IFNG, CXCL10, and CXCL11 expression (p < 0.001; p < 0.005, and 0.01, respectively) were detected, whereas no differences were observed in the control group.

Conclusion: Gene expression of Th1 response mediators is higher during ACR. Triple IS group showed significantly lower expression of pro-inflammatory Th1 mediators during mild ACR indicating that use of these markers to monitor rejection can be affected by the IS treatment used.

Keywords: gene expression; immunosuppression; interferon gamma; intestinal transplant; rejection.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Biomarkers / analysis*
  • Case-Control Studies
  • Chemokine CXCL10 / genetics*
  • Chemokine CXCL11 / genetics*
  • Female
  • Follow-Up Studies
  • Graft Rejection / drug therapy
  • Graft Rejection / genetics
  • Graft Rejection / immunology*
  • Humans
  • Immunosuppressive Agents / therapeutic use*
  • Interferon-gamma / genetics*
  • Intestinal Diseases / surgery
  • Intestine, Small / transplantation*
  • Male
  • Postoperative Complications
  • Prognosis
  • Real-Time Polymerase Chain Reaction
  • Risk Factors
  • Th1 Cells / immunology*

Substances

  • Biomarkers
  • CXCL10 protein, human
  • CXCL11 protein, human
  • Chemokine CXCL10
  • Chemokine CXCL11
  • IFNG protein, human
  • Immunosuppressive Agents
  • Interferon-gamma