The 2013 International Society for Heart and Lung Transplantation Working Formulation for the standardization of nomenclature in the pathologic diagnosis of antibody-mediated rejection in heart transplantation

Antibody-Mediated Rejection in Lung Transplantation: Clinical Outcomes and Donor-Specific Antibody Characteristics

“…The diagnostic criteria for AMR in those solid organ transplants (SOTs) are robust and well established (3,4), with specific subtypes of rejection now being deciphered based on molecular microscopy (5-7) or outcome studies of large populations (8,9). In contrast, diagnosis of AMR in the context lung transplantation (LT) remains a challenging concern that has been highlighted by different groups (10,11).…”

Practical Applications in Immunohistochemistry: Evaluation of Rejection and Infection in Organ Transplantation

“…In 2013, the International Society for Heart & Lung Transplantation (ISHLT, Addison, Texas) published a ''working formulation'' to standardize pathologic diagnosis and nomenclature of ABMR, based on accumulated data in the literature, consensus conferences, and workshops, and reviewed in several recent publications. 13,[67][68][69] The current pathologic diagnostic construct relies on histologic evidence of microvascular injury (see Table 1) as well as immunophenotypic criteria on biopsy and no longer requires organ dysfunction or (unlike kidney) serologic evidence of donorspecific antibodies. 13 However, clinicopathologic correlation remains paramount for patient management, and diagnostic criteria will evolve.…”

“…13,[67][68][69] The current pathologic diagnostic construct relies on histologic evidence of microvascular injury (see Table 1) as well as immunophenotypic criteria on biopsy and no longer requires organ dysfunction or (unlike kidney) serologic evidence of donorspecific antibodies. 13 However, clinicopathologic correlation remains paramount for patient management, and diagnostic criteria will evolve.…”

“…13,28,70 As in other allograft organs, antibody and C4 activation at, and C4d deposition on, the endothelium of the microvasculature is the diagnostically significant pattern. In heart, microvasculature includes the network of interstitial capillaries between cardiac myocytes, and any other labeling is considered nonspecific, including the endothelium or elastica of larger arteries, capillaries in Quilty lesions, capillaries in areas of fibrosis, necrotic myocytes, subendocardial connective tissue, and luminal reactivity (serum) in vessels of any size.…”

“…In general, evaluation of ABMR typically requires correlation of histologic findings (evidence of tissue damage, which often manifests as intracapillary inflammatory cells, termed capillaritis, see Table 1), immunostaining (C4d deposition in capillaries as a hallmark of antibody-mediated damage), and immunologic data (presence of donor-specific antibodies that may remain elusive in the case of non-HLA antibodies). [7][8][9][10][11][12][13][14] Many antibody reagents are available for detection of C4d deposits in transplant biopsies (sampled in Table 2). Some of these reagents are best applied to frozen tissue with immunofluorescence (IF) detection; others are applicable to formalin-fixed, paraffin-embedded tissue, with immunohistochemical (IHC)/immunoperoxidase (IP) detection, or both.…”