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

In the context of lung transplant (LT), because of diagnostic difficulties, antibody‐mediated rejection (AMR) remains a matter of debate. We retrospectively analyzed an LT cohort at Foch Hospital to demonstrate the impact of AMR on LT prognosis. AMR diagnosis requires association of clinical symptoms, donor‐specific antibodies (DSAs), and C4d+ staining and/or histological patterns consistent with AMR. Prospective categorization split patients into four groups: (i) DSA positive, AMR positive (DSAposAMRpos); (ii) DSA positive, AMR negative (DSAposAMRneg); (iii) DSA limited, AMR negative (DSALim; equal to one specificity, with mean fluorescence intensity of 500–1000 once); and (iv) DSA negative, AMR negative (DSAneg). AMR treatment consisted of a combination of plasmapheresis, intravenous immunoglobulin and rituximab. Among 206 transplanted patients, 10.7% were DSAposAMRpos (n = 22), 40.3% were DSAposAMRneg (n = 84), 6% were DSALim (n = 13) and 43% were DSAneg (n = 88). Analysis of acute cellular rejection at month 12 showed higher cumulative numbers (mean plus or minus standard deviation) in the DSAposAMRpos group (2.1 ± 1.7) compared with DSAposAMRneg (1 ± 1.2), DSALim (0.75 ± 1), and DSAneg (0.7 ± 1.23) groups. Multivariate analysis demonstrated AMR as a risk factor for chronic lung allograft dysfunction (hazard ratio [HR] 8.7) and graft loss (HR 7.56) for DSAposAMRpos patients. Our results show a negative impact of AMR on LT clinical course and advocate for an early active diagnostic approach and evaluation of therapeutic strategies to improve prognosis.