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Banff 2013

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Monica M. Colvin-Adams, MD
University of Minnesota
Minneapolis, Minnesota, USA

The 12th Banff Conference on Allograft Pathology was held in Comandatuba-Bahia, Brazil this year. After 2 flights, a 1-hour car ride, and a ferry, we arrived on the beautiful, heavily palm-treed island of Comandatuba. Scuttled away amidst the monkeys and the ocean, my memories of Minnesota faded away as I planned my new career tie-dying beach coverups. But our determined leader, Rene Rodriguez, brought us back to reality as the goal of the tropical trip was to work. And so we did.

links imageAlthough only a small portion of the conference was dedicated to cardiac transplant pathology, the discussions proved to be stimulating and informative. The heart transplant session was led by Rene Rodriguez (Section Head Anatomic Pathology, Cleveland Clinic) and Carmela Tan (Anatomic Pathology, Cleveland Clinic) with contributions from Gerald Berry (Professor of Pathology, Stanford), Martin Goddard (Consultant Histolopathologist and Clinical Director of Pathology, Papworth Hospital), Dolly Tyan (Professor of Pathology, Stanford), Janet Scheel (Medical Director Heart Failure and Transplant, Children's National Heart Institute) and myself.

Dr. Berry provided an update on the revised ISHLT AMR grading system and Dr. Goddard discussed the pitfalls of using immunohistochemistry. Dr. Tyan with usual clarity and zeal, provided a primer on donor-specific antibodies and C1Q testing, providing momentary lucidity for the immunologically-challenged amongst us (ahem). The take away: C1Q may clarify "important" antibodies in patients who are sensitized and may improve access to donors by allowing clinicians to eliminate non-complement activating antibodies when listing. Dr. Scheel presented several cases of CAV though to be secondary to AMR and reviewed some of the differences and challenges in diagnosing and treating AMR in pediatric heart transplant recipients. She also reviewed the present multi-center collaborative research in progress on allo-antibodies in these patients. links imageThe aim of these studies is to increase the understanding of the AMR including the role of cytoprotective genes, anti MICA and adhesion molecules. The youngest patients have the best graft survival, and hopefully with a better understanding of AMR, we can improve these outcomes even further in these young patients who have the most to gain. I focused on remaining issues in the diagnosis and treatment of AMR in adults.

What did we accomplish? The focus of the heart section was on the newly adapted criteria for diagnosing antibody-mediated rejection in heart transplant. This was clearly a great accomplishment but to keep the field moving, we turned our attention to the unknown: what is the significance of a positive C4d only? How can we distinguish subclinical AMR from accommodation? What are the remaining challenges for pediatric and adult patients?

To that end, Dr. Tan provided data regarding the natural history of C4d+ staining (immunofluorescence) in heart allografts. Most of these cases have no allograft dysfunction, and morphologically cannot be designated accommodation versus subclinical AMR; however in a prospective study of a large cohort, 17% of C4d+ cases progressed to C4d+ and C3d+. The consequences of C4d+ remain unknown although these are cases that may bear observation.

links imageThe 2013 ISHLT Working Formulation for AMR, which was accepted for publication in JHLT, was discussed. In the evolving formulation, it is proposed that the diagnosis of AMR be based on histologic changes on H&E stained sections, if present, and immunohistochemistry or immunofluorescence. The usefulness of histologic diagnosis of AMR, including microvascular inflammation, was discussed with illustrative cases. The category pAMR1(H+), characterized by histologic but not immunohistologic evidence of AMR, is not known. The category pAMR1(I+) refers to cases with immunopathologic evidence of AMR, by immunofluorescence or immunohistochemistry, but no evidence on routine histology. Since immunohistochemistry users do not report C3d, this category cannot differentiate between C4d+/C3d+ and C4d+ only.

While the proposed criteria for diagnosing AMR clarify the pathologic criteria, it prevents pathologists from considering donor specific antibodies and graft function in the diagnostic criteria. Thus, challenges remain even with the new grading system as we seek to understand the subtler findings of immune activation and their management.

While the main focus was on the new pathologic criteria, other provocative ideas were raised:

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Clearly, there is much to learn and multicenter collaboration is key. It is worth mentioning that in addition to the 2013 ISHLT Working Formulation for AMR (JHLT), there are several papers addressing AMR in heart transplant on the horizon. The Banff 2013 consensus paper has been accepted for publication in the American Journal of Transplantation and the AHA commissioned a statement on AMR that is in the final stages.

It is December in Minnesota and I am about as far from Comandatuba as I can possibly be yet if I shut the blinds, turn up the heat, and close my eyes really tight, I can still hear the waves crashing on the beach.

Special thanks to Rene Rodriguez and Janet Scheel for their contributions.

Disclosure Statement: The author has no conflicts of interest to report.

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