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Chronic rejection of a lung transplant is characterized by a profile of specific autoantibodies
Author(s) -
Hagedorn Peter H.,
Burton Christopher M.,
Carlsen Jørn,
Steinbrüchel Daniel,
Andersen Claus B.,
Sahar Eli,
Domany Eytan,
Cohen Irun R.,
Flyvbjerg Henrik,
Iversen Martin
Publication year - 2010
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/j.1365-2567.2010.03246.x
Subject(s) - autoantibody , bronchiolitis obliterans , immunology , autoimmunity , lung transplantation , pathogenesis , antigen , lung , pathological , antibody , medicine , biology , pathology
Summary 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.