Association of Clonal Hematopoiesis of Indeterminate Potential with Inflammatory Gene Expression in Patients with COPD

Stefan Kuhnert; Siavash Mansouri; Michael A Rieger; Rajkumar Savai; Edibe Avci; Gabriela Díaz-Piña; Manju Padmasekar; Mario Looso; Stefan Hadzic; Till Acker; Stephan Klatt; Jochen Wilhelm; Ingrid Fleming; Natascha Sommer; Norbert Weissmann; Claus Vogelmeier; Robert Bals; Andreas Zeiher; Stefanie Dimmeler; Werner Seeger; Soni S Pullamsetti

doi:10.3390/cells11132121

Association of Clonal Hematopoiesis of Indeterminate Potential with Inflammatory Gene Expression in Patients with COPD

Cells. 2022 Jul 5;11(13):2121. doi: 10.3390/cells11132121.

Authors

Stefan Kuhnert¹, Siavash Mansouri², Michael A Rieger^{3

4}, Rajkumar Savai^{1

2

4

5}, Edibe Avci², Gabriela Díaz-Piña², Manju Padmasekar², Mario Looso², Stefan Hadzic¹, Till Acker⁶, Stephan Klatt⁷, Jochen Wilhelm^{1

5}, Ingrid Fleming⁷, Natascha Sommer¹, Norbert Weissmann^{1

5}, Claus Vogelmeier⁸, Robert Bals⁹, Andreas Zeiher¹⁰, Stefanie Dimmeler¹¹, Werner Seeger^{1

2

5}, Soni S Pullamsetti^{1

2

5}

Affiliations

¹ University of Giessen and Marburg Lung Center (UGMLC), German Center for Lung Research (DZL), Cardio-Pulmonary Institute (CPI), Justus Liebig University, 35392 Giessen, Germany.
² Max Planck Institute for Heart and Lung Research, DZL, CPI, 61231 Bad Nauheim, Germany.
³ Department of Medicine, Hematology/Oncology, University Hospital Frankfurt, CPI, Goethe University, 60596 Frankfurt am Main, Germany.
⁴ Frankfurt Cancer Institute (FCI), CPI, Goethe University, 60596 Frankfurt am Main, Germany.
⁵ Institute for Lung Health (ILH), Justus Liebig University, 35392 Giessen, Germany.
⁶ Institute for Neuropathology, CPI, Justus Liebig University, 35392 Giessen, Germany.
⁷ Institute of Vascular Signalling, Department of Molecular Medicine, CPI, Goethe University, 60596 Frankfurt am Main, Germany.
⁸ Department of Medicine, Pulmonary and Critical Care Medicine, Philipps University of Marburg, DZL, 35043 Marburg, Germany.
⁹ Department of Internal Medicine V-Pulmonology, Allergology and Critical Care Medicine, Saarland University, 66421 Homburg, Germany.
¹⁰ Department of Medicine, Cardiology, CPI, Goethe University Hospital, 60596 Frankfurt am Main, Germany.
¹¹ Institute for Cardiovascular Regeneration, CPI, Goethe University, 60596 Frankfurt am Main, Germany.

Abstract

Chronic obstructive pulmonary disease (COPD) is a disease with an inflammatory phenotype with increasing prevalence in the elderly. Expanded population of mutant blood cells carrying somatic mutations is termed clonal hematopoiesis of indeterminate potential (CHIP). The association between CHIP and COPD and its relevant effects on DNA methylation in aging are mainly unknown. Analyzing the deep-targeted amplicon sequencing from 125 COPD patients, we found enhanced incidence of CHIP mutations (~20%) with a predominance of DNMT3A CHIP-mediated hypomethylation of Phospholipase D Family Member 5 (PLD5), which in turn is positively correlated with increased levels of glycerol phosphocholine, pro-inflammatory cytokines, and deteriorating lung function.

Keywords: COPD; clonal hematopoiesis; inflammation.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aged
Clonal Hematopoiesis*
Gene Expression
Hematopoiesis / genetics
Humans
Mutation / genetics
Pulmonary Disease, Chronic Obstructive* / genetics

Grants and funding

This work was supported by the Max Planck Society, the Cardio-Pulmonary Institute (CPI), the German Center for Lung Research (DZL), and the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation)—Project number 268555672—SFB 1213 (Project A01, A05 to SSP, A07 to NW and Project A10* to RS) and European Research Council (ERC) Consolidator Grant (#866051 to SSP).