title: Antibody-Mediated Rejection in Lung Transplantation: Clinical Outcomes and Donor-Specific Antibody Characteristics.
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 (DSA(pos) AMR(pos) ); (ii) DSA positive, AMR negative (DSA(pos) AMR(neg) ); (iii) DSA limited, AMR negative (DSA(Lim) ; equal to one specificity, with mean fluorescence intensity of 500-1000 once); and (iv) DSA negative, AMR negative (DSA(neg) ). AMR treatment consisted of a combination of plasmapheresis, intravenous immunoglobulin and rituximab. Among 206 transplanted patients, 10.7% were DSA(pos) AMR(pos) (n = 22), 40.3% were DSA(pos) AMR(neg) (n = 84), 6% were DSA(Lim) (n = 13) and 43% were DSA(neg) (n = 88). Analysis of acute cellular rejection at month 12 showed higher cumulative numbers (mean plus or minus standard deviation) in the DSA(pos) AMR(pos) group (2.1 ± 1.7) compared with DSA(pos) AMR(neg) (1 ± 1.2), DSA(Lim) (0.75 ± 1), and DSA(neg) (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 DSA(pos) AMR(pos) 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.
authors: Pneumology, Adult Cystic Fibrosis Center and Lung Transplantation Department, Foch Hospital, Suresnes, France.|Department of Pathology and Laboratory Medicine, University of California Los Angeles, Los Angeles, CA.|Université Versailles Saint-Quentin-en-Yvelines, UPRES EA220, Suresnes, France.
authors: A
authors: A
authors: Roux
authors: Pneumology, Adult Cystic Fibrosis Center and Lung Transplantation Department, Foch Hospital, Suresnes, France.
authors: I
authors: I
authors: Bendib Le Lan
authors: Pathology Department, Foch Hospital, Suresnes, France.
authors: S
authors: S
authors: Holifanjaniaina
authors: Department of Pathology and Laboratory Medicine, University of California Los Angeles, Los Angeles, CA.
authors: K A
authors: KA
authors: Thomas
authors: Pneumology, Adult Cystic Fibrosis Center and Lung Transplantation Department, Foch Hospital, Suresnes, France.
authors: A M
authors: AM
authors: Hamid
authors: Pneumology, Adult Cystic Fibrosis Center and Lung Transplantation Department, Foch Hospital, Suresnes, France.
authors: C
authors: C
authors: Picard
authors: Pneumology, Adult Cystic Fibrosis Center and Lung Transplantation Department, Foch Hospital, Suresnes, France.
authors: D
authors: D
authors: Grenet
authors: Pneumology, Adult Cystic Fibrosis Center and Lung Transplantation Department, Foch Hospital, Suresnes, France.
authors: S
authors: S
authors: De Miranda
authors: Pneumology, Adult Cystic Fibrosis Center and Lung Transplantation Department, Foch Hospital, Suresnes, France.
authors: B
authors: B
authors: Douvry
authors: Pneumology, Adult Cystic Fibrosis Center and Lung Transplantation Department, Foch Hospital, Suresnes, France.
authors: L
authors: L
authors: Beaumont-Azuar
authors: Université Versailles Saint-Quentin-en-Yvelines, UPRES EA220, Suresnes, France.|Thoracic Surgery Department, Foch Hospital, Suresnes, France.
authors: E
authors: E
authors: Sage
authors: Intensive Care Unit, Foch Hospital, Suresnes, France.
authors: J
authors: J
authors: Devaquet
authors: Thoracic Intensive Care Unit, Foch Hospital, Suresnes, France.
authors: E
authors: E
authors: Cuquemelle
authors: Anesthesiology Department, Foch Hospital, Suresnes, France.
authors: M
authors: M
authors: Le Guen
authors: Department of Microbiology,Immunology and Molecular Genetics, University of California Los Angeles, Los Angeles, CA.|Institute for Quantitative and Computational Biosciences, University of California Los Angeles, Los Angeles, CA.
authors: R
authors: R
authors: Spreafico
authors: Laboratoire Régional d'Histocompatibilité, Saint-Louis Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France.
authors: C
authors: C
authors: Suberbielle-Boissel
authors: Pneumology, Adult Cystic Fibrosis Center and Lung Transplantation Department, Foch Hospital, Suresnes, France.
authors: M
authors: M
authors: Stern
authors: Thoracic Intensive Care Unit, Foch Hospital, Suresnes, France.
authors: F
authors: F
authors: Parquin
mesh_terms: D000328:Adult; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000209:etiology*; D006085:Graft Survival / Q000276:immunology*; D006680:HLA Antigens / Q000276:immunology; D006801:Humans; D007518:Isoantibodies / Q000276:immunology*; D008171:Lung Diseases / Q000276:immunology / Q000601:surgery*; D016040:Lung Transplantation; D008297:Male; D008875:Middle Aged; D011183:Postoperative Complications; D011379:Prognosis; D011446:Prospective Studies; D012307:Risk Factors; D014019:Tissue Donors; D055815:Young Adult
chemical_list: D006680:HLA Antigens; D007518:Isoantibodies
keywords: clinical research, practice; health services and outcomes research