Autoantibodies against the chemokine receptor 3 predict cardiovascular risk

  1. Müller, Felix Steffen ORCID logo
  2. Aherrahrou, Zouhair ORCID logo
  3. Grasshoff, Hanna ORCID logo
  4. Heidorn, Marc ORCID logo
  5. Humrich, Jens ORCID logo
  6. Johanson, Laurence
  7. Aherrahrou, Redouane ORCID logo
  8. Reinberger, Tobias ORCID logo
  9. Schulz, Andreas
  10. Ten Cate, Vincent ORCID logo
  11. Pallares Robles, Alejandro ORCID logo
  12. Koeck, Thomas ORCID logo
  13. Rapp, Steffen ORCID logo
  14. Lange, Tanja ORCID logo
  15. Brachaczek, Lukas
  16. Luebber, Finn ORCID logo
  17. Erdmann, Jeanette ORCID logo
  18. Heidecke, Harald
  19. Schulze-Forster, Kai
  20. Dechend, Ralf ORCID logo
  21. Lackner, Karl J
  22. Pfeiffer, Norbert ORCID logo
  23. Ghaemi Kerahrodi, Jasmin
  24. Tuescher, Oliver ORCID logo
  25. Schwarting, Andreas ORCID logo
  26. Strauch, Konstantin ORCID logo
  27. Muenzel, Thomas ORCID logo
  28. Prochaska, Jürgen ORCID logo
  29. Riemekasten, Gabriela ORCID logo
  30. Wild, Philipp ORCID logo

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WeightNameValue
1000 Titel
  • Autoantibodies against the chemokine receptor 3 predict cardiovascular risk
1000 Autor/in
  1. Müller, Felix Steffen |
  2. Aherrahrou, Zouhair |
  3. Grasshoff, Hanna |
  4. Heidorn, Marc |
  5. Humrich, Jens |
  6. Johanson, Laurence |
  7. Aherrahrou, Redouane |
  8. Reinberger, Tobias |
  9. Schulz, Andreas |
  10. Ten Cate, Vincent |
  11. Pallares Robles, Alejandro |
  12. Koeck, Thomas |
  13. Rapp, Steffen |
  14. Lange, Tanja |
  15. Brachaczek, Lukas |
  16. Luebber, Finn |
  17. Erdmann, Jeanette |
  18. Heidecke, Harald |
  19. Schulze-Forster, Kai |
  20. Dechend, Ralf |
  21. Lackner, Karl J |
  22. Pfeiffer, Norbert |
  23. Ghaemi Kerahrodi, Jasmin |
  24. Tuescher, Oliver |
  25. Schwarting, Andreas |
  26. Strauch, Konstantin |
  27. Muenzel, Thomas |
  28. Prochaska, Jürgen |
  29. Riemekasten, Gabriela |
  30. Wild, Philipp |
1000 Erscheinungsjahr 2023
1000 LeibnizOpen
1000 Publikationstyp
  1. Artikel |
1000 Online veröffentlicht
  • 2023-11-06
1000 Erschienen in
1000 Quellenangabe
  • 44(47):4935-4949
1000 FRL-Sammlung
1000 Copyrightjahr
  • 2023
1000 Lizenz
1000 Verlagsversion
  • https://doi.org/10.1093/eurheartj/ehad666 |
  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10719496/ |
1000 Publikationsstatus
1000 Begutachtungsstatus
1000 Sprache der Publikation
1000 Abstract/Summary
  • Background and aims!#!Chronic inflammation and autoimmunity contribute to cardiovascular (CV) disease. Recently, autoantibodies (aAbs) against the CXC-motif-chemokine receptor 3 (CXCR3), a G protein-coupled receptor with a key role in atherosclerosis, have been identified. The role of anti-CXCR3 aAbs for CV risk and disease is unclear.!##!Methods!#!Anti-CXCR3 aAbs were quantified by a commercially available enzyme-linked immunosorbent assay in 5000 participants (availability: 97.1%) of the population-based Gutenberg Health Study with extensive clinical phenotyping. Regression analyses were carried out to identify determinants of anti-CXCR3 aAbs and relevance for clinical outcome (i.e. all-cause mortality, cardiac death, heart failure, and major adverse cardiac events comprising incident coronary artery disease, myocardial infarction, and cardiac death). Last, immunization with CXCR3 and passive transfer of aAbs were performed in ApoE(-/-) mice for preclinical validation.!##!Results!#!The analysis sample included 4195 individuals (48% female, mean age 55.5 ± 11 years) after exclusion of individuals with autoimmune disease, immunomodulatory medication, acute infection, and history of cancer. Independent of age, sex, renal function, and traditional CV risk factors, increasing concentrations of anti-CXCR3 aAbs translated into higher intima-media thickness, left ventricular mass, and N-terminal pro-B-type natriuretic peptide. Adjusted for age and sex, anti-CXCR3 aAbs above the 75th percentile predicted all-cause death [hazard ratio (HR) (95% confidence interval) 1.25 (1.02, 1.52), P = .029], driven by excess cardiac mortality [HR 2.51 (1.21, 5.22), P = .014]. A trend towards a higher risk for major adverse cardiac events [HR 1.42 (1.0, 2.0), P = .05] along with increased risk of incident heart failure [HR per standard deviation increase of anti-CXCR3 aAbs: 1.26 (1.02, 1.56), P = .03] may contribute to this observation. Targeted proteomics revealed a molecular signature of anti-CXCR3 aAbs reflecting immune cell activation and cytokine-cytokine receptor interactions associated with an ongoing T helper cell 1 response. Finally, ApoE(-/-) mice immunized against CXCR3 displayed increased anti-CXCR3 aAbs and exhibited a higher burden of atherosclerosis compared to non-immunized controls, correlating with concentrations of anti-CXCR3 aAbs in the passive transfer model.!##!Conclusions!#!In individuals free of autoimmune disease, anti-CXCR3 aAbs were abundant, related to CV end-organ damage, and predicted all-cause death as well as cardiac morbidity and mortality in conjunction with the acceleration of experimental atherosclerosis.
1000 Sacherschließung
lokal Cardiovascular Diseases/epidemiology
lokal Aged [MeSH]
lokal Atherosclerosis
lokal Risk Factors [MeSH]
lokal Autoantibodies/immunology [MeSH]
lokal Heart Failure
lokal Female
lokal Mice
lokal Heart Disease Risk Factors [MeSH]
lokal Male [MeSH]
lokal Apolipoproteins E [MeSH]
lokal Heart Disease Risk Factors
lokal Carotid Intima-Media Thickness
lokal Autoimmune Diseases
lokal Female [MeSH]
lokal Humans
lokal Receptors, Chemokine
lokal Receptors, Chemokine [MeSH]
lokal Carotid Intima-Media Thickness [MeSH]
lokal Adult [MeSH]
lokal Autoantibodies/blood [MeSH]
lokal Humans [MeSH]
lokal Receptors, CXCR3/immunology [MeSH]
lokal Cardiology and Cardiovascular Medicine
lokal Adult
lokal Middle Aged
lokal Cardiovascular Diseases/epidemiology [MeSH]
lokal Heart Failure [MeSH]
lokal Middle Aged [MeSH]
lokal Animals [MeSH]
lokal Receptors, CXCR3/immunology
lokal Mice [MeSH]
lokal Autoimmune Diseases [MeSH]
lokal Male
lokal Cardiovascular Diseases/blood [MeSH]
lokal Apolipoproteins E
lokal Autoantibodies/blood
lokal Animals
lokal Autoantibodies/immunology
lokal Atherosclerosis [MeSH]
lokal Risk Factors
lokal Aged
lokal Cardiovascular Diseases/blood
1000 Fächerklassifikation (DDC)
1000 Liste der Beteiligten
  1. https://orcid.org/0000-0002-7328-1056|https://orcid.org/0000-0002-1241-8733|https://orcid.org/0000-0003-1395-3268|https://orcid.org/0000-0003-0134-2726|https://orcid.org/0000-0003-3111-2788|https://frl.publisso.de/adhoc/uri/Sm9oYW5zb24sIExhdXJlbmNl|https://orcid.org/0000-0001-8148-9554|https://orcid.org/0000-0002-6237-0803|https://frl.publisso.de/adhoc/uri/U2NodWx6LCBBbmRyZWFz|https://orcid.org/0000-0003-3285-8442|https://orcid.org/0000-0003-0352-4179|https://orcid.org/0000-0002-0379-5836|https://orcid.org/0000-0003-0463-5380|https://orcid.org/0000-0001-8309-2112|https://frl.publisso.de/adhoc/uri/QnJhY2hhY3playwgTHVrYXM=|https://orcid.org/0000-0003-0893-2120|https://orcid.org/0000-0002-4486-6231|https://frl.publisso.de/adhoc/uri/SGVpZGVja2UsIEhhcmFsZA==|https://frl.publisso.de/adhoc/uri/U2NodWx6ZS1Gb3JzdGVyLCBLYWk=|https://orcid.org/0000-0001-6636-3080|https://frl.publisso.de/adhoc/uri/TGFja25lciwgS2FybCBK|https://orcid.org/0000-0002-5766-2617|https://frl.publisso.de/adhoc/uri/R2hhZW1pIEtlcmFocm9kaSwgSmFzbWlu|https://orcid.org/0000-0002-4023-5301|https://orcid.org/0000-0002-0566-598X|https://orcid.org/0000-0002-1814-5860|https://orcid.org/0000-0001-5503-4150|https://orcid.org/0000-0001-5078-9992|https://orcid.org/0000-0002-5406-2464|https://orcid.org/0000-0003-4413-9752
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