Myocardial HLA-G Reliably Indicates a Low Risk of Acute Cellular Rejection in Heart Transplant Recipients

Sheshgiri, Rohit; Rouas-Freiss, Nathalie; Rao, Vivek; Butany, Jagdish; Ramzy, Danny; Krawice-Radanne, Irene; Ross, Heather J.; Carosella, Edgardo D.; Delgado, Diego H.

doi:10.1016/j.healun.2008.02.004

« Previous Next »The Journal of Heart and Lung Transplantation
Volume 27, Issue 5 , Pages 522-527, May 2008

Myocardial HLA-G Reliably Indicates a Low Risk of Acute Cellular Rejection in Heart Transplant Recipients

Rohit Sheshgiri
- Heart Transplant Program, Peter Munk Cardiac Centre, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada
Nathalie Rouas-Freiss, PhD
- Service de Recherches en Hemato-Immunologie, CEA-DSV-DRM, Hopital Saint Louis, IUH, Paris, France.
Vivek Rao, MD, PhD
- Heart Transplant Program, Peter Munk Cardiac Centre, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada
Jagdish Butany, MD
- Heart Transplant Program, Peter Munk Cardiac Centre, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada
Danny Ramzy, MD, PhD
- Heart Transplant Program, Peter Munk Cardiac Centre, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada
Irene Krawice-Radanne
- Service de Recherches en Hemato-Immunologie, CEA-DSV-DRM, Hopital Saint Louis, IUH, Paris, France.
Heather J. Ross, MD, MHSc
- Heart Transplant Program, Peter Munk Cardiac Centre, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada
Edgardo D. Carosella, MD
- Service de Recherches en Hemato-Immunologie, CEA-DSV-DRM, Hopital Saint Louis, IUH, Paris, France.
Diego H. Delgado, MD, MSc
- Heart Transplant Program, Peter Munk Cardiac Centre, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada
- Reprint requests: Diego Hernan Delgado, MD, Division of Cardiology, Department of Medicine, Toronto General Hospital, 585 University Avenue, NCSB 11C-1201, Toronto, ON M5G 2N2, Canada. Telephone: 416-340-3940. Fax: 416-340-4134.

Received 22 October 2007; received in revised form 20 January 2008; accepted 6 February 2008.

Background

Human leukocyte antigen-G (HLA-G), a non-classical MHC I protein with restricted tissue expression, plays an essential role in immune tolerance and has been negatively associated with acute and chronic rejection after heart transplantation. We assessed myocardial HLA-G expression in adult heart transplant patients in an attempt to determine the value of this protein in identifying patients with a low risk of acute cellular rejection.

Methods

Two groups of patients were included in this study. Group A (non-rejecting) included 29 patients who had no moderate or severe rejection episodes (ISHLT Grade <2R) post-transplant. Group B (rejecting) included 38 patients with at least two moderate or severe rejection episodes (Grade ≥2R) within a 1-year period. Expression of HLA-G in three myocardial biopsies post-transplant from each patient was determined through immunohistochemical staining.

Results

In Group A, 86% of patients had HLA-G⁺ biopsies compared with 11% of patients in Group B (p < 0.001; sensitivity 86%, specificity 87%). Whereas 60% of non-rejecting HLA-G⁺ patients had at least two positive biopsies, all rejecting HLA-G⁺ patients had only one positive biopsy.

Conclusions

There is a significant negative association between myocardial HLA-G expression and acute cellular rejection after cardiac transplantation. Detection of HLA-G appears to reliably indicate a low risk of developing moderate or severe allograft rejection and may, subsequently, allow for a reduced immunosuppressive regimen.