Chronic rejection of a lung transplant is characterized by a profile of specific autoantibodies

Peter Hagedorn; Christopher Malcolm Burton; Jørn Carlsen; Daniel Steinbrüchel; Claus B Andersen; Eli Sahar; Eytan Domany; Irun R Cohen; Henrik Flyvbjerg; Martin Iversen

doi:10.1111/j.1365-2567.2010.03246.x

Chronic rejection of a lung transplant is characterized by a profile of specific autoantibodies

Peter Hagedorn, Christopher Malcolm Burton, Jørn Carlsen, Daniel Steinbrüchel, Claus B Andersen, Eli Sahar, Eytan Domany, Irun R Cohen, Henrik Flyvbjerg, Martin Iversen

26 Citations (Scopus)

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.

Original language	English
Journal	Immunology
Volume	130
Issue number	3
Pages (from-to)	427-35
Number of pages	9
ISSN	0019-2805
DOIs	https://doi.org/10.1111/j.1365-2567.2010.03246.x
Publication status	Published - 1 Jul 2010

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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.",

author = "Peter Hagedorn and Burton, {Christopher Malcolm} and J{\o}rn Carlsen and Daniel Steinbr{\"u}chel and Andersen, {Claus B} and Eli Sahar and Eytan Domany and Cohen, {Irun R} and Henrik Flyvbjerg and Martin Iversen",

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doi = "10.1111/j.1365-2567.2010.03246.x",

language = "English",

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T1 - Chronic rejection of a lung transplant is characterized by a profile of specific autoantibodies

AU - Hagedorn, Peter

AU - Burton, Christopher Malcolm

AU - Carlsen, Jørn

AU - Steinbrüchel, Daniel

AU - Andersen, Claus B

AU - Sahar, Eli

AU - Domany, Eytan

AU - Cohen, Irun R

AU - Flyvbjerg, Henrik

AU - Iversen, Martin

PY - 2010/7/1

Y1 - 2010/7/1

N2 - 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.

AB - 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.

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DO - 10.1111/j.1365-2567.2010.03246.x

M3 - Journal article

SN - 0953-4954

VL - 130

SP - 427

EP - 435

JO - Immunology. Supplement

JF - Immunology. Supplement

IS - 3

ER -

Chronic rejection of a lung transplant is characterized by a profile of specific autoantibodies

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