Research
Print page Print page
Switch language
The Capital Region of Denmark - 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

  1. Frequency and immunophenotype of IL10-producing regulatory B cells in optic neuritis

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. More tricks with tetramers: a practical guide to staining T cells with peptide-MHC multimers

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. Dietary gluten alters the balance of pro-inflammatory and anti-inflammatory cytokines in T cells of BALB/c mice

    Research output: Contribution to journalJournal articleResearchpeer-review

  4. Identification of MHC class II restricted T-cell-mediated reactivity against MHC class I binding Mycobacterium tuberculosis peptides

    Research output: Contribution to journalJournal articleResearchpeer-review

  1. Impact of CMV PCR Blips in Recipients of Solid Organ and Hematopoietic Stem Cell Transplantation

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Cytomegalovirus Viral Load in Bronchoalveolar Lavage to Diagnose Lung Transplant Associated CMV Pneumonia

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. Laser-capture microdissection, mass spectrometry and immunohistochemistry reveal pathologic alterations in the extracellular matrix of transplanted lungs

    Research output: Contribution to conferenceConference abstract for conferenceResearchpeer-review

View graph of relations
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.
Original languageEnglish
JournalImmunology
Volume132
Issue number3
Pages (from-to)394-400
Number of pages7
ISSN0019-2805
DOIs
Publication statusPublished - 2011

    Research areas

  • Adult, Aged, Autoantibodies, Autoantigens, Female, Gene Expression, Gene Expression Profiling, Humans, Lung Transplantation, Male, Middle Aged, Primary Graft Dysfunction, Tissue Donors

ID: 33267475