title: Chronic rejection of a lung transplant is characterized by a profile of specific autoantibodies.
abstract: Obliterative bronchiolitis (OB) continues to be the major limitation to long-term survival after lung transplantation. The specific aetiology and pathogenesis of OB are not well understood. To explore the role of autoreactivity in OB, we spotted 751 different self molecules onto glass slides, and used these antigen microarrays to profile 48 human serum samples for immunoglobulin G (IgG) and IgM autoantibodies; 27 patients showed no or mild bronchiolitis obliterans syndrome (BOS; a clinical correlate of OB) and 15 patients showed medium to severe BOS. We now report that these BOS grades could be differentiated by a profile of autoantibodies binding to 28 proteins or their peptides. The informative autoantibody profile included down-regulation as well as up-regulation of both IgM and IgG specific reactivities. This profile was evaluated for robustness using a panel of six independent test patients. Analysis of the functions of the 28 informative self antigens showed that eight of them are connected in an interaction network involved in apoptosis and protein metabolism. Thus, a profile of autoantibodies may reflect pathological processes in the lung allograft, suggesting a role for autoimmunity in chronic rejection leading to OB.
authors.affiliation: Biosystems Department, Risø National Laboratory, Technical University of Denmark, Roskilde, Denmark. hagedorn@cbs.dtu.dk
authors.forename: Peter H
authors.initials: PH
authors.lastname: Hagedorn
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Burton
authors.forename: Jørn
authors.initials: J
authors.lastname: Carlsen
authors.forename: Daniel
authors.initials: D
authors.lastname: Steinbrüchel
authors.forename: Claus B
authors.initials: CB
authors.lastname: Andersen
authors.forename: Eli
authors.initials: E
authors.lastname: Sahar
authors.forename: Eytan
authors.initials: E
authors.lastname: Domany
authors.forename: Irun R
authors.initials: IR
authors.lastname: Cohen
authors.forename: Henrik
authors.initials: H
authors.lastname: Flyvbjerg
authors.forename: Martin
authors.initials: M
authors.lastname: Iversen
mesh_terms: D000328:Adult; D017209:Apoptosis / Q000502:physiology; D001323:Autoantibodies / Q000097:blood / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology; D001794:Blood Pressure / Q000502:physiology; D001989:Bronchiolitis Obliterans / Q000175:diagnosis* / Q000209:etiology / Q000276:immunology*; D002633:Chemotaxis / Q000502:physiology; D018450:Disease Progression; D005260:Female; D006084:Graft Rejection / Q000150:complications / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D007075:Immunoglobulin M / Q000097:blood / Q000276:immunology; D016040:Lung Transplantation / Q000276:immunology*; D008297:Male; D053858:Metabolic Networks and Pathways / Q000502:physiology; D046228:Microarray Analysis; D008875:Middle Aged; D025341:Principal Component Analysis; D011506:Proteins / Q000276:immunology / Q000378:metabolism
chemical_list: D001323:Autoantibodies; D001324:Autoantigens; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D011506:Proteins