Frontiers in Immunology (Oct 2023)
Integrated Immunopeptidomic and Proteomic Analysis of COVID-19 lung biopsies
- Shanye Yin,
- Shanye Yin,
- Susan Klaeger,
- Vipheaviny A. Chea,
- Vipheaviny A. Chea,
- Isabel P. Carulli,
- Isabel P. Carulli,
- Suzanna Rachimi,
- Katharine E. Black,
- Katharine E. Black,
- Michael Filbin,
- Michael Filbin,
- Lida P. Hariri,
- Lida P. Hariri,
- Lida P. Hariri,
- Rachel S. Knipe,
- Rachel S. Knipe,
- Robert F. Padera,
- Robert F. Padera,
- Jonathan D. Stevens,
- William J. Lane,
- William J. Lane,
- Steven A. Carr,
- Catherine J. Wu,
- Catherine J. Wu,
- Catherine J. Wu,
- Catherine J. Wu,
- Edy Yong Kim,
- Edy Yong Kim,
- Derin B. Keskin,
- Derin B. Keskin,
- Derin B. Keskin,
- Derin B. Keskin,
- Derin B. Keskin,
- Derin B. Keskin
Affiliations
- Shanye Yin
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, United States
- Shanye Yin
- Harvard Medical School, Boston, MA, United States
- Susan Klaeger
- Broad Institute of MIT and Harvard, Cambridge, MA, United States
- Vipheaviny A. Chea
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, United States
- Vipheaviny A. Chea
- Translational Immunogenomics Laboratory, Dana-Farber Cancer Institute, Boston, MA, United States
- Isabel P. Carulli
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, United States
- Isabel P. Carulli
- Translational Immunogenomics Laboratory, Dana-Farber Cancer Institute, Boston, MA, United States
- Suzanna Rachimi
- Broad Institute of MIT and Harvard, Cambridge, MA, United States
- Katharine E. Black
- Harvard Medical School, Boston, MA, United States
- Katharine E. Black
- Division of Pulmonary and Critical Care Medicine, Massachusetts General Hospital, Boston, MA, United States
- Michael Filbin
- Harvard Medical School, Boston, MA, United States
- Michael Filbin
- Department of Emergency Medicine, Massachusetts General Hospital, Boston, MA, United States
- Lida P. Hariri
- Harvard Medical School, Boston, MA, United States
- Lida P. Hariri
- Division of Pulmonary and Critical Care Medicine, Massachusetts General Hospital, Boston, MA, United States
- Lida P. Hariri
- Department of Pathology, Massachusetts General Hospital, Boston, MA, United States
- Rachel S. Knipe
- Harvard Medical School, Boston, MA, United States
- Rachel S. Knipe
- Division of Pulmonary and Critical Care Medicine, Massachusetts General Hospital, Boston, MA, United States
- Robert F. Padera
- Harvard Medical School, Boston, MA, United States
- Robert F. Padera
- Department of Pathology, Brigham and Women’s Hospital, Boston, MA, United States
- Jonathan D. Stevens
- Department of Pathology, Brigham and Women’s Hospital, Boston, MA, United States
- William J. Lane
- Harvard Medical School, Boston, MA, United States
- William J. Lane
- Department of Pathology, Brigham and Women’s Hospital, Boston, MA, United States
- Steven A. Carr
- Broad Institute of MIT and Harvard, Cambridge, MA, United States
- Catherine J. Wu
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, United States
- Catherine J. Wu
- Harvard Medical School, Boston, MA, United States
- Catherine J. Wu
- Broad Institute of MIT and Harvard, Cambridge, MA, United States
- Catherine J. Wu
- Department of Medicine, Brigham and Women’s Hospital, Boston, MA, United States
- Edy Yong Kim
- Harvard Medical School, Boston, MA, United States
- Edy Yong Kim
- 0Division of Pulmonary and Critical Care Medicine, Brigham and Women’s Hospital, Boston, MA, United States
- Derin B. Keskin
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, United States
- Derin B. Keskin
- Harvard Medical School, Boston, MA, United States
- Derin B. Keskin
- Broad Institute of MIT and Harvard, Cambridge, MA, United States
- Derin B. Keskin
- Translational Immunogenomics Laboratory, Dana-Farber Cancer Institute, Boston, MA, United States
- Derin B. Keskin
- 1Section for Bioinformatics, Department of Health Technology, Technical University of Denmark, Lyngby, Denmark
- Derin B. Keskin
- 2Department of Computer Science, Metropolitan College, Boston University, Boston, MA, United States
- DOI
- https://doi.org/10.3389/fimmu.2023.1269335
- Journal volume & issue
-
Vol. 14
Abstract
IntroductionSevere respiratory illness is the most prominent manifestation of patients infected with SARS-CoV-2, and yet the molecular mechanisms underlying severe lung disease in COVID-19 affected patients still require elucidation. Human leukocyte antigen class I (HLA-I) expression is crucial for antigen presentation and the host’s response to SARS-CoV-2.MethodsTo gain insights into the immune response and molecular pathways involved in severe lung disease, we performed immunopeptidomic and proteomic analyses of lung tissues recovered at four COVID-19 autopsy and six non-COVID-19 transplants.ResultsWe found signals of tissue injury and regeneration in lung fibroblast and alveolar type I/II cells, resulting in the production of highly immunogenic self-antigens within the lungs of COVID-19 patients. We also identified immune activation of the M2c macrophage as the primary source of HLA-I presentation and immunogenicity in this context. Additionally, we identified 28 lung signatures that can serve as early plasma markers for predicting infection and severe COVID-19 disease. These protein signatures were predominantly expressed in macrophages and epithelial cells and were associated with complement and coagulation cascades.DiscussionOur findings emphasize the significant role of macrophage-mediated immunity in the development of severe lung disease in COVID-19 patients.
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