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Gerald J Berry, MD
Immediate Past Chair, ISHLT Pathology Council

gerald berryThere continues to be growing multidisciplinary interest in the problem of antibody-mediated rejection in pulmonary transplant recipients. There are challenges in clinical detection, histopathological manifestations, immunophenotypic profiles, serological characterizations and patient management.

From the pathologist's perspective, definitions and diagnostic criteria are difficult to extract from the published literature. Most pathologists in busy transplant centers have encountered a few or perhaps a handful of cases that demonstrate either histopathological patterns that resemble previously published cases, nonspecific morphologies but with clinical and/or serological data that support the diagnosis of AMR, or patients with graft dysfunction that responded to AMR-directed therapies such as plasmaphoresis.

With this background of experiences, the Pathology Council initiated a survey of current practices in the diagnosis and reporting of pulmonary AMR. A web-based survey was sent to over 40 centers in North America, Europe and Australia achieving a high rate of response. At a workshop held on April 17, 2012 as part of the 32nd Annual Meeting and Scientific Sessions in Prague, a group of transplant pathologists convened to discuss the results of the survey to develop a consensus approach to histopathological and immunophenotypic criteria for the diagnosis of AMR and the standardization of terminology for the reporting of AMR.

Technical issues that were discussed included the establishment of primary antibody panels for paraffin section immunohistochemistry. Among the interpretative issues that were delineated were the structural components for antibody assessment, thresholds of interpretation of both intensity and distribution of antibody staining and terminology for reporting positive and negative cases. The group affirmed that histopathological patterns previously described in AMR can be observed in a variety of disorders including severe acute cellular rejection, infection, graft preservation injury and drug reactions. A list of histopathological indications for further immunopathological work-up and evaluation was developed.

Most importantly it was also emphasized that the diagnosis of AMR requires a multidisciplinary approach and input including clinical, serological and pathological findings. Pathologists are encouraged to work closely with their clinicians and immunologists to develop protocols to coordinate donor-specific antibody analysis (DSA) with biopsy immunophenotyping. A multidisciplinary protocol approach to the study of AMR will promote future investigations that address issues of time of onset of AMR after transplant, incidence and prevalence, the spectrum of temporal, morphological and immunopathological changes and the clinical outcome and risk for developing chronic allograft dysfunction.

Finally, the Pathology Council seeks to promote educational and collaborative efforts utilizing digital pathology and virtual microscopy as a means to share both classic and diagnostically challenging cases, evaluate and refine diagnostic criteria related to morphological patterns and immunophenotypic staining profiles of established antibodies and the development of potential new markers for the diagnosis of pulmonary AMR.

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