New ISHLT nomenclature & diagnostic criteria: Antibody-mediated rejection in heart transplantation

November 18, 2013

New York, NY, November 18, 2013 - Antibody-mediated rejection of the transplanted heart is a recognized clinical complication and a major limitation to survival of patients who have undergone heart transplantation. Experts have now developed a new working formulation for the pathologic diagnosis, grading, and reporting of cardiac antibody-mediated rejection. Their consensus statement is published in the December issue of The Journal of Heart and Lung Transplantation and is freely available at

Heart transplantation is the definitive therapy for eligible patients with end-stage heart failure. However, antibody-mediated rejection (AMR) of a cardiac allograft -- a heart from a genetically non-identical donor - is a recognized clinical complication in the management of heart transplant patients and can develop more than a year after transplantation has occurred.

Over the past 25 years experts have wrestled to establish practical working definitions to guide the diagnosis, grading, and reporting of AMR. In the initial 1990 International Society for Heart Transplantation (ISHLT) working formulation, "positive immunofluorescence, vasculitis, or severe edema in the absence of cellular infiltrates" were proposed as the key diagnostic hallmarks. This working formulation included the qualified recommendation that "centers routinely performing immunofluorescence should consider staining all endomyocardial biopsy specimens obtained in the first six weeks following transplantation." More detailed histopathologic features and immunopathologic criteria were proposed in the follow-up 2005 ISHLT revision of nomenclature and diagnostic criteria.

In 2010 the increasing awareness of asymptomatic AMR and its association with accelerated cardiac allograft vasculopathy and increased mortality, together with the need to define a therapeutic strategy, led an international multidisciplinary group to recommend the removal of the clinical and serologic components specified in the 2005 working formulation as requirements for the diagnosis of AMR. The biopsy tissue diagnosis of cardiac AMR has since been established by using agreed reproducible histopathologic and immunopathologic criteria akin to the diagnosis of acute cellular rejection (ACR).

In this statement, members of the Pathology Council of ISHLT led by Gerald J. Berry, MD, Professor of Pathology, Stanford University School of Medicine, and Director, Cardiac and Pulmonary Pathology, Stanford University Hospital and Clinics and Lucile Packard Children's Hospital at Stanford, reports the consensus findings from a series of meetings held between 2010 and 2012 to develop a new working formulation for the pathologic diagnosis, grading, and reporting of cardiac AMR.

"Tremendous progress has been achieved over the last decade in recognizing, diagnosing and grading AMR, but its recognition and diagnosis by histopathology, even among experienced transplant pathologists, is challenging," says Berry. "With the rapid changes that occur in medicine, new and more specific antibodies--or even new technologies--may provide more accurate and reproducible results for the diagnosis of AMR. Until then, there remain numerous challenges and unresolved clinical, immunologic, and pathologic questions. It is our distinct intention and hope that the diagnostic criteria and grading scheme presented in this working formulation will aid in the resolution of these and other issues."

The report covers: The Working Group points out that this document reflects the current state of knowledge and experience of transplant pathologists, and also serves as a framework for the organization of future multicenter studies. Areas pinpointed as needing further evaluation include AMR in children and the threshold for therapeutic intervention in patients with "asymptomatic AMR."

Elsevier Health Sciences

Related Transplantation Articles from Brightsurf:

A revolutionary new treatment alternative to corneal transplantation
A new approach in ophthalmology that offers a revolutionary alternative to corneal transplantation has just been developed by researchers and clinicians in North America, Europe, and Oceania.

Fewer complications after organ transplantation
A large international study coordinated by University Hospital Regensburg and Charité - Universitätsmedizin Berlin has demonstrated the safety of new cell therapy approaches for use in kidney transplant recipients.

Elderly patients also benefit from kidney transplantation
So far, kidney transplantation has generally not been offered to elderly patients (>75 years) because of the perioperative risks.

New material will allow abandoning bone marrow transplantation
Scientists from the National University of Science and Technology 'MISIS' developed nanomaterial, which will be able to restore the internal structure of bones damaged due to osteoporosis and osteomyelitis.

Fewer medical tests -- timely listing for transplantation
Younger patients would benefit greatly from kidney transplantation. Their expected remaining lifetime may even be doubled by having a transplant.

Uterus transplantation -- ethically just as problematic as altruistic surrogacy
In 2014, the first child to have been gestated in a donated uterus was born.

Advancing transplantation: Hepatitis C-infected organs safe for transplantation when followed by antiviral treatment
Twenty patients at Penn Medicine have been cured of the hepatitis C virus (HCV) following lifesaving kidney transplants from deceased donors who were infected with the disease, according to a study published today in Annals of Internal Medicine.

Transplantation followed by antiviral therapy cured hepatitis C
Twenty patients who received kidneys transplanted from hepatitis C virus (HCV)-infected donors experienced HCV cure, good quality of life, and excellent renal function at one year.

The Journal of Heart and Lung Transplantation: 50 years of heart transplantation progress
This month marks the 50th anniversary of the world's first human heart transplant performed at Groote Schuur Hospital in Cape Town by South African surgeon, Christiaan Barnard.

Older donor lungs should be considered for transplantation
With a scarcity of lungs available for transplantation, the use of lungs from donors older than age 60 has been shown to achieve reasonable outcomes and should be considered as a viable option, according to research published online today in The Annals of Thoracic Surgery.

Read More: Transplantation News and Transplantation Current Events is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to