Research
Print page Print page
Switch language
Rigshospitalet - a part of Copenhagen University Hospital
Published

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

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

APA

CBE

MLA

Vancouver

Author

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. 2011 ; Vol. 132, No. 3. pp. 394-400.

Bibtex

@article{13f960b0ab40460b9abf05979b1dea4c,
title = "Integrative analysis correlates donor transcripts to recipient autoantibodies in primary graft dysfunction after lung transplantation",
abstract = "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 x 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.",
keywords = "Adult, Aged, Autoantibodies, Autoantigens, Female, Gene Expression, Gene Expression Profiling, Humans, Lung Transplantation, Male, Middle Aged, Primary Graft Dysfunction, Tissue Donors",
author = "Peter Hagedorn and Burton, {Christopher M} and Eli Sahar and Eytan Domany and Cohen, {Irun R} and Henrik Flyvbjerg and Martin Iversen",
note = "{\textcopyright} 2010 The Authors. Immunology {\textcopyright} 2010 Blackwell Publishing Ltd.",
year = "2011",
doi = "10.1111/j.1365-2567.2010.03373.x",
language = "English",
volume = "132",
pages = "394--400",
journal = "Immunology",
issn = "0019-2805",
publisher = "Wiley-Blackwell Publishing Ltd",
number = "3",

}

RIS

TY - JOUR

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

AU - Hagedorn, Peter

AU - Burton, Christopher M

AU - Sahar, Eli

AU - Domany, Eytan

AU - Cohen, Irun R

AU - Flyvbjerg, Henrik

AU - Iversen, Martin

N1 - © 2010 The Authors. Immunology © 2010 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 x 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 x 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 - Adult

KW - Aged

KW - Autoantibodies

KW - Autoantigens

KW - Female

KW - Gene Expression

KW - Gene Expression Profiling

KW - Humans

KW - Lung Transplantation

KW - Male

KW - Middle Aged

KW - Primary Graft Dysfunction

KW - Tissue Donors

U2 - 10.1111/j.1365-2567.2010.03373.x

DO - 10.1111/j.1365-2567.2010.03373.x

M3 - Journal article

C2 - 21070236

VL - 132

SP - 394

EP - 400

JO - Immunology

JF - Immunology

SN - 0019-2805

IS - 3

ER -

ID: 33267475