Diagnosis of Acute Cellular Rejection and Antibody-Mediated Rejection on Lung Transplant Biopsies: A Perspective From Members of the Pulmonary Pathology Society

Abstract

Context.— The diagnosis and grading of acute cellular and antibody-mediated rejection (AMR) in lung allograft biopsies is important because rejection can lead to acute graft dysfunction and/or failure and may contribute to chronic graft failure. While acute cellular rejection is well defined histologically, no reproducible specific features of AMR are currently identified. Therefore, a combination of clinical features, serology, histopathology, and immunologic findings is suggested for the diagnosis of AMR. Objective.— To describe the perspective of members of the Pulmonary Pathology Society (PPS) on the workup of lung allograft transbronchial biopsy and the diagnosis of acute cellular rejection and AMR in lung transplant. Data Sources.— Reports by the International Society for Heart and Lung Transplantation (ISHLT), experience of members of PPS who routinely review lung allograft biopsies, and search of literature database (PubMed). Conclusions.— Acute cellular rejection should be assessed and graded according to the 2007 working formulation of the ISHLT. As currently no specific features are known for AMR in lung allografts, the triple test (clinical allograft dysfunction, donor-specific antibodies, pathologic findings) should be used for its diagnosis. C4d staining might be performed when morphologic, clinical, and/or serologic features suggestive of AMR are identified.

Evaluation of current strategies for surveillance and management of donor‐specific antibodies: Single‐center study

“…The presence and role of C4d, a complement split product, in lung allograft is unclear, in part because the reproducibility of C4d results has been problematic . In addition, C4d deposition can be seen in any other process associated with complement activation, highlighting its lack of specificity for DSA‐related processes. In our study, we found no difference in C4d staining in DSA positive or negative groups supporting the consensus from earlier reports …”

“…In addition, C4d deposition can be seen in any other process associated with complement activation, highlighting its lack of specificity for DSA‐related processes. In our study, we found no difference in C4d staining in DSA positive or negative groups supporting the consensus from earlier reports …”

“…According to previously defined pathologic criteria, acute cellular rejection was graded from A1 to A4. The cumulative acute rejection (CAR) score represents the sum of each individual acute rejection score.…”

“…All recipients underwent surveillance bronchoscopy at 1, 3, 6, and 12 months after transplant. All episodes of acute rejection were diagnosed histologically according to ISHLT criteria . The presence of acute cellular rejection was determined based on review of pathology reports from transbronchial biopsy specimens.…”

Bronchoalveolar lavage cytokines are of minor value to diagnose complications following lung transplantation

“…Non-invasive tests like pulmonary function testing and chest imaging are useful indicators for potential complications, but have no discriminatory value between ACR and infection [9]. For these reasons, transbronchial biopsies (TBB) remain the gold standard for the diagnosis of ACR [10]. However, TBB are invasive and bear potential risks such as pneumothorax or bleeding [11,12].…”