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Integrative analysis correlates donor transcripts to recipient autoantibodies in primary graft dysfunction after lung transplantation. / Hagedorn, Peter; Burton, Christopher M.; Sahar, Eli; Domany, Eytan; Cohen, Irun R.; Flyvbjerg, Henrik; Iversen, Martin.

In: Immunology, Vol. 132, No. 3, 2011, p. 394-400.

Publication: Research - peer-reviewJournal article – Annual report year: 2011

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Hagedorn, Peter; Burton, Christopher M.; Sahar, Eli; Domany, Eytan; Cohen, Irun R.; Flyvbjerg, Henrik; Iversen, Martin / Integrative analysis correlates donor transcripts to recipient autoantibodies in primary graft dysfunction after lung transplantation.

In: Immunology, Vol. 132, No. 3, 2011, p. 394-400.

Publication: Research - peer-reviewJournal article – Annual report year: 2011

Bibtex

@article{6ff23c9da6d5416c96f04df3176b7dbe,
title = "Integrative analysis correlates donor transcripts to recipient autoantibodies in primary graft dysfunction after lung transplantation",
keywords = "uden tema",
publisher = "Wiley-Blackwell Publishing Ltd.",
author = "Peter Hagedorn and Burton, {Christopher M.} and Eli Sahar and Eytan Domany and Cohen, {Irun R.} and Henrik Flyvbjerg and Martin Iversen",
year = "2011",
doi = "10.1111/j.1365-2567.2010.03373.x",
volume = "132",
number = "3",
pages = "394--400",
journal = "Immunology",
issn = "0019-2805",

}

RIS

TY - JOUR

T1 - Integrative analysis correlates donor transcripts to recipient autoantibodies in primary graft dysfunction after lung transplantation

A1 - Hagedorn,Peter

A1 - Burton,Christopher M.

A1 - Sahar,Eli

A1 - Domany,Eytan

A1 - Cohen,Irun R.

A1 - Flyvbjerg,Henrik

A1 - Iversen,Martin

AU - Hagedorn,Peter

AU - Burton,Christopher M.

AU - Sahar,Eli

AU - Domany,Eytan

AU - Cohen,Irun R.

AU - Flyvbjerg,Henrik

AU - Iversen,Martin

PB - Wiley-Blackwell Publishing Ltd.

PY - 2011

Y1 - 2011

N2 - Up to one in four lung‐transplanted patients develop pulmonary infiltrates and impaired oxygenation within the first days after lung transplantation. Known as primary graft dysfunction (PGD), this condition increases mortality significantly. Complex interactions between donor lung and recipient immune system are the suspected cause. We took an integrative, systems‐level approach by first exploring whether the recipient’s immune response to PGD includes the development of long‐lasting autoreactivity. We next explored whether proteins displaying such differential autoreactivity also display differential gene expression in donor lungs that later develop PGD compared with those that did not. We evaluated 39 patients from whom autoantibody profiles were already available for PGD based on chest radiographs and oxygenation data. An additional nine patients were evaluated for PGD based on their medical records and set aside for validation. From two recent donor lung gene expression studies, we reanalysed and paired gene profiles with autoantibody profiles. Primary graft dysfunction can be distinguished by a profile of differentially reactive autoantibodies binding to 17 proteins. Functional analysis showed that 12 of these proteins are part of a protein–protein interaction network (P = 3 × 10−6) involved in proliferative processes. A nearest centroid classifier assigned correct PGD grades to eight out of the nine patients in the validation cohort (P = 0·048). We observed significant positive correlation (r = 0·63, P = 0·011) between differences in IgM reactivity and differences in gene expression levels. This connection between donor lung gene expression and long‐lasting recipient IgM autoantibodies towards a specific set of proteins suggests a mechanism for the development of autoimmunity in PGD.

AB - Up to one in four lung‐transplanted patients develop pulmonary infiltrates and impaired oxygenation within the first days after lung transplantation. Known as primary graft dysfunction (PGD), this condition increases mortality significantly. Complex interactions between donor lung and recipient immune system are the suspected cause. We took an integrative, systems‐level approach by first exploring whether the recipient’s immune response to PGD includes the development of long‐lasting autoreactivity. We next explored whether proteins displaying such differential autoreactivity also display differential gene expression in donor lungs that later develop PGD compared with those that did not. We evaluated 39 patients from whom autoantibody profiles were already available for PGD based on chest radiographs and oxygenation data. An additional nine patients were evaluated for PGD based on their medical records and set aside for validation. From two recent donor lung gene expression studies, we reanalysed and paired gene profiles with autoantibody profiles. Primary graft dysfunction can be distinguished by a profile of differentially reactive autoantibodies binding to 17 proteins. Functional analysis showed that 12 of these proteins are part of a protein–protein interaction network (P = 3 × 10−6) involved in proliferative processes. A nearest centroid classifier assigned correct PGD grades to eight out of the nine patients in the validation cohort (P = 0·048). We observed significant positive correlation (r = 0·63, P = 0·011) between differences in IgM reactivity and differences in gene expression levels. This connection between donor lung gene expression and long‐lasting recipient IgM autoantibodies towards a specific set of proteins suggests a mechanism for the development of autoimmunity in PGD.

KW - uden tema

U2 - 10.1111/j.1365-2567.2010.03373.x

DO - 10.1111/j.1365-2567.2010.03373.x

JO - Immunology

JF - Immunology

SN - 0019-2805

IS - 3

VL - 132

SP - 394

EP - 400

ER -