{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T09:07:16Z","timestamp":1791882436484,"version":"4.3.4"},"reference-count":49,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2015,11,25]],"date-time":"2015-11-25T00:00:00Z","timestamp":1448409600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Dutch Arthritis Foundation"},{"name":"NWO (Zenith grant)"},{"name":"NWO Vidi grant"},{"name":"European Research Council Starting Investigator Grant"},{"DOI":"10.13039\/501100001505","name":"Health Research Council of New Zealand","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100001505","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100013459","name":"Arthritis New Zealand","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100013459","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatology"],"published-print":{"date-parts":[[2015,12]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>The frequent association of gout with metabolic syndrome and cardiovascular disease (CVD) suggests that it has a systemic component. Our objective was to study whether circulating proinflammatory cytokines are associated with comorbidities in gout patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We studied 330 gout patients from 3 independent cohorts and compared them with 144 healthy individuals and 276 disease controls. We measured circulating levels of interleukin\u20108 (IL\u20108)\/CXCL8, IL\u20101\u03b2, IL\u20106, IL\u201010, IL\u201012, and tumor necrosis factor, after which we performed proteome\u2010wide analysis in a selection of samples to identify proteins that were possibly prognostic for the development of comorbidities. Replication analysis was performed specifically for myeloid\u2010related protein 8 (MRP\u20108)\/MRP\u201014 complex.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Compared to healthy controls and disease control patients, patients with gouty arthritis (n\u2009=\u200948) had significantly higher mean levels of CXCL8 (<jats:italic>P<\/jats:italic> &lt; 0.001), while other cytokines were almost undetectable. Similarly, patients with intercritical gout showed high levels of CXCL8. CXCL8 was independently associated with diabetes mellitus in patients with intercritical gout (<jats:italic>P<\/jats:italic> &lt; 0.0001). Proteome\u2010wide analysis in gouty arthritis (n\u2009=\u200918) and intercritical gout (n\u2009=\u200939) revealed MRP\u20108 and MRP\u201014 as the proteins with the greatest differential expression between low and high levels of CXCL8 and also showed a positive correlation of MRP8\/MRP14 complex with CXCL8 levels (R<jats:sup>2<\/jats:sup>\u2009=\u20090.49, <jats:italic>P<\/jats:italic> &lt; 0.001). These findings were replicated in an independent cohort. The proteome of gout patients with high levels of CXCL8 was associated with diabetes mellitus (odds ratio 16.5 [95% confidence interval 2.8\u201396.6]) and CVD (odds ratio 3.9 [95% confidence interval 1.0\u201315.3]).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Circulating levels of CXCL8 are increased during both the acute and intercritical phases of gout, and they coincide with a specific circulating proteome that is associated with risk of diabetes mellitus and CVD. Further research focused on the roles of CXCL8 and MRP8\/MRP14 complex in patients with gout is warranted.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.39318","type":"journal-article","created":{"date-parts":[[2015,8,5]],"date-time":"2015-08-05T21:47:04Z","timestamp":1438811224000},"page":"3303-3313","source":"Crossref","is-referenced-by-count":59,"title":["Gout Is a Chronic Inflammatory Disease in Which High Levels of Interleukin\u20108 (CXCL8), Myeloid\u2010Related Protein 8\/Myeloid\u2010Related Protein 14 Complex, and an Altered Proteome Are Associated With Diabetes Mellitus and Cardiovascular Disease"],"prefix":"10.1002","volume":"67","author":[{"given":"Laura B. E.","family":"Kienhorst","sequence":"first","affiliation":[{"name":"Rijnstate Hospital Arnhem The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ellen","family":"van Lochem","sequence":"additional","affiliation":[{"name":"Rijnstate Hospital Arnhem The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wietske","family":"Kievit","sequence":"additional","affiliation":[{"name":"Radboud University Medical Center  Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola","family":"Dalbeth","sequence":"additional","affiliation":[{"name":"University of Auckland  Auckland New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marilyn E.","family":"Merriman","sequence":"additional","affiliation":[{"name":"University of Otago  Dunedin New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda","family":"Phipps\u2010Green","sequence":"additional","affiliation":[{"name":"University of Otago  Dunedin New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arnoud","family":"Loof","sequence":"additional","affiliation":[{"name":"Radboud University Medical Center  Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Waander","family":"van Heerde","sequence":"additional","affiliation":[{"name":"Radboud University Medical Center  Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sita","family":"Vermeulen","sequence":"additional","affiliation":[{"name":"Radboud University Medical Center  Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa K.","family":"Stamp","sequence":"additional","affiliation":[{"name":"University of Otago  Christchurch New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elly","family":"van Koolwijk","sequence":"additional","affiliation":[{"name":"Rijnstate Hospital Arnhem The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacqueline","family":"de Graaf","sequence":"additional","affiliation":[{"name":"Radboud University Medical Center  Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dirk","family":"Holzinger","sequence":"additional","affiliation":[{"name":"University Hospital Muenster  Muenster Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes","family":"Roth","sequence":"additional","affiliation":[{"name":"University Hospital Muenster  Muenster Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hein J. 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