Am J Transplant. 2016 Feb 4. doi: 10.1111/ajt.13589. [Epub ahead of print]

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

Roux A1,2,3, Bendib Le Lan I1, Holifanjaniaina S4, Thomas KA2, Hamid AM1, Picard C1, Grenet D1, De Miranda S1, Douvry B1, Beaumont-Azuar L1, Sage E3,5,Devaquet J6, Cuquemelle E7, Le Guen M8, Spreafico R9,10, Suberbielle-Boissel C11, Stern M1, Parquin F7; Foch Lung Transplantation Group.

Author information

• 1Pneumology, Adult Cystic Fibrosis Center and Lung Transplantation Department, Foch Hospital, Suresnes, France.
• 2Department of Pathology and Laboratory Medicine, University of California Los Angeles, Los Angeles, CA.
• 3Université Versailles Saint-Quentin-en-Yvelines, UPRES EA220, Suresnes, France.
• 4Pathology Department, Foch Hospital, Suresnes, France.
• 5Thoracic Surgery Department, Foch Hospital, Suresnes, France.
• 6Intensive Care Unit, Foch Hospital, Suresnes, France.
• 7Thoracic Intensive Care Unit, Foch Hospital, Suresnes, France.
• 8Anesthesiology Department, Foch Hospital, Suresnes, France.
• 9Department of Microbiology,Immunology and Molecular Genetics, University of California Los Angeles, Los Angeles, CA.
• 10Institute for Quantitative and Computational Biosciences, University of California Los Angeles, Los Angeles, CA.
• 11Laboratoire Régional d'Histocompatibilité, Saint-Louis Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France.

Abstract

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 (DSApos AMRpos ); (ii) DSA positive, AMR negative (DSApos AMRneg ); (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 DSApos AMRpos (n = 22), 40.3% were DSApos AMRneg (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 DSApos AMRposgroup (2.1 ± 1.7) compared with DSApos AMRneg (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 DSApos AMRpos 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.