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A Systemic Inflammatory Signature Reflecting Cross Talk Between Innate and Adaptive Immunity Is Associated With Incident Polyneuropathy: KORA F4/FF4 Study

  1. Christian Herder1,2⇑3,
  2. Julia M. Kannenberg1,2,
  3. Maren Carstensen-Kirberg1,2,
  4. Alexander Strom1,2,
  5. Gidon J. Bönhof1,
  6. Wolfgang Rathmann2,4,
  7. Cornelia Huth2,5,
  8. Wolfgang Koenig6,7,8,
  9. Margit Heier5,
  10. Jan Krumsiek2,9,10,
  11. Annette Peters2,5,
  12. Christa Meisinger2,5,11,
  13. Michael Roden1,2,3,
  14. Barbara Thorand2,5 and
  15. Dan Ziegler1,2,3
  1. 1Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany
  2. 2German Center for Diabetes Research (DZD), München-Neuherberg, Germany
  3. 3Division of Endocrinology and Diabetology, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
  4. 4Institute for Biometrics and Epidemiology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany
  5. 5Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany
  6. 6Deutsches Herzzentrum München, Technische Universität München, Munich, Germany
  7. 7German Center for Cardiovascular Research (DZHK), Partner site Munich Heart Alliance, Munich, Germany
  8. 8Department of Internal Medicine II-Cardiology, University of Ulm Medical Center, Ulm, Germany
  9. 9Institute of Computational Biology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany
  10. 10Department of Physiology and Biophysics, Institute for Computational Biomedicine, Englander Institute for Precision Medicine, Weill Cornell Medicine, New York, NY
  11. 11Chair of Epidemiology, Ludwig-Maximilians-Universität München am UNIKA-T Augsburg, Augsburg, Germany
  1. Corresponding author: Christian Herder, christian.herder{at}ddz.uni-duesseldorf.de.
  1. B.T. and D.Z. contributed equally to this work.

Diabetes 2018 Nov; 67(11): 2434-2442. https://doi.org/10.2337/db18-0060
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Abstract

Prospective analyses of biomarkers of inflammation and distal sensorimotor polyneuropathy (DSPN) are scarce and limited to innate immunity. We therefore aimed to assess associations between biomarkers reflecting multiple aspects of immune activation and DSPN. The study was based on 127 case subjects with incident DSPN and 386 noncase subjects from the population-based Cooperative Health Research in the Region of Augsburg (KORA) F4/FF4 cohort (follow-up 6.5 years). Proximity extension assay technology was used to measure serum levels of biomarkers of inflammation. Of 71 biomarkers assessed, 26 were associated with incident DSPN. After adjustment for multiple testing, higher levels of six biomarkers remained related to incident DSPN. Three of these proteins (MCP-3/CCL7, MIG/CXCL9, IP-10/CXCL10) were chemokines, and the other three (DNER, CD40, TNFRSF9) were soluble forms of transmembrane receptors. The chemokines had neurotoxic effects on neuroblastoma cells in vitro. Addition of all six biomarkers improved the C statistic of a clinical risk model from 0.748 to 0.783 (P = 0.011). Pathway analyses indicated that multiple cell types from innate and adaptive immunity are involved in the development of DSPN. We thus identified novel associations between biomarkers of inflammation and incident DSPN pointing to a complex cross talk between innate and adaptive immunity in the pathogenesis of the disease.

Footnotes

  • This article contains Supplementary Data online at http://diabetes.diabetesjournals.org/lookup/suppl/doi:10.2337/db18-0060/-/DC1.

  • Received January 15, 2018.
  • Accepted August 6, 2018.
  • © 2018 by the American Diabetes Association.
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A Systemic Inflammatory Signature Reflecting Cross Talk Between Innate and Adaptive Immunity Is Associated With Incident Polyneuropathy: KORA F4/FF4 Study
Christian Herder, Julia M. Kannenberg, Maren Carstensen-Kirberg, Alexander Strom, Gidon J. Bönhof, Wolfgang Rathmann, Cornelia Huth, Wolfgang Koenig, Margit Heier, Jan Krumsiek, Annette Peters, Christa Meisinger, Michael Roden, Barbara Thorand, Dan Ziegler
Diabetes Nov 2018, 67 (11) 2434-2442; DOI: 10.2337/db18-0060

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A Systemic Inflammatory Signature Reflecting Cross Talk Between Innate and Adaptive Immunity Is Associated With Incident Polyneuropathy: KORA F4/FF4 Study
Christian Herder, Julia M. Kannenberg, Maren Carstensen-Kirberg, Alexander Strom, Gidon J. Bönhof, Wolfgang Rathmann, Cornelia Huth, Wolfgang Koenig, Margit Heier, Jan Krumsiek, Annette Peters, Christa Meisinger, Michael Roden, Barbara Thorand, Dan Ziegler
Diabetes Nov 2018, 67 (11) 2434-2442; DOI: 10.2337/db18-0060
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