Prevalence of Antibody Mediated Rejection in Lung Transplant Recipients with Clinical Dysfunction and/or Histological Damage: The PADOVA Experience

Abstract

Purpose: Antibody-mediated rejection (AMR) following lung transplantation (LTX) is an evolving concept that may explain persistent graft dysfunction or organ failure in a subset of patients. The incidence of lung AMR is unknown and the clinical outcome has been reported only in a few studies. Methods: Forty-one lung recipients were included in the study: 24 with clinical dysfunction and/or histological indications for AMR immunopathologic evaluation and 17 controls (without signs of clinical dysfunction and histological damage). All patients underwent scheduled transbronchial biopsies or biopsies for clinical indication, associated with screening for the detection of donor-specific anti-HLA antibodies (DSA) by luminex. AMR was defined according the latest AMR update from the ISHLT Pathology Council [Berry G et al., 2013]. Patients with AMR were treated with high-dose steroids, plasmapheresis and CMV-Ig. Results: During the follow up, 59 biopsies and DSA measurements were performed; 3 patients showed acute AMR (defined as high DSA levels and C4d immunostaining in more than 50% of interstitial capillaries) and one showed probable AMR (C4d > 50% but no DSA). AMR occurred very early (within 4 months after LTX) and these patients elicited a de novo anti-DQ immune response. They were followed for a mean follow-up time of 17 months (range: 10-24 months) and 7 biopsies and blood samples taken at the same time for each patient were analyzed. One patient died 4 weeks after diagnosis for untreatable AMR; in one patient AMR lasted for 6 months and one patient showed clinical improvement with considerable DSA reduction after 5 weeks. The 17 control patients without clinical or histological signs of graft damage had no pathological C4d deposition or DSA in the measurements performed to date. Conclusion: Our data show that, in lung transplant recipients with clinical dysfunction and/or histological damage, AMR is not a rare event as it has a prevalence of 12.5%. In these patients a full clinical, pathological and immunological assessment should be performed to enable a timely diagnosis and a better therapeutic approach of this challenging form of rejection.