Diagnosis of antibody-mediated rejection (AMR) on lung transplant biopsies: A retrospective single-center case study

AMR is increasingly recognized as an important form of lung rejection and contrary to its cellular counterpart it lacks specific features. Diagnostic criteria according to ISHLT guidelines include clinical evidence of graft dysfunction, presence of de novo donor-specific antibodies (DSAs) and histology suggestive of AMR with or without deposition of complement 4d (C4d). We examined the incidence of AMR as a clinical indication for biopsy between 2011 and 2017. In this period 736/49 patients underwent lung transplant/retransplantation procedures at the Vienna General Hospital. In the first year after surgery AMR was suspected in 22 out of 82 patients who developed allograft dysfunction. We observed DSAs in these 22 patients prior to or concomitantly with diagnostic biopsy. No evidence of higher-grade cellular rejection, infection, drug reactions or other injuries was seen in these patients. Histologic features included diffuse alveolar damage (DAD) (n=15), capillaritis (n=3) and neutrophilic septal margination (n=2). C4d deposition in the endothelium (50% or more capillaries stained) was seen in 5 grafts. Out of 22 patients with DSAs diagnostic certainty of AMR was ‘definite’ in 5 ‘probable’ in 10 and ‘possible’ in 7. Although any process associated with complement activation can induce C4d deposition, positive staining without other proof of AMR was rarely seen in our collective. The only 2 cases presented as DAD related to severe infection and higher-grade (A2) cellular rejection. We concluded from this study that definite AMR according to ISHLT is a rare occurrence in our center and that the majority of cases with suspected AMR rank as probable/possible.