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Gout Is a Chronic Inflammatory Disease in Which High Levels of Interleukin‐8 (CXCL8), Myeloid‐Related Protein 8/Myeloid‐Related Protein 14 Complex, and an Altered Proteome Are Associated With Diabetes Mellitus and Cardiovascular Disease
Author(s) -
Kienhorst Laura B. E.,
van Lochem Ellen,
Kievit Wietske,
Dalbeth Nicola,
Merriman Marilyn E.,
PhippsGreen Amanda,
Loof Arnoud,
van Heerde Waander,
Vermeulen Sita,
Stamp Lisa K.,
van Koolwijk Elly,
de Graaf Jacqueline,
Holzinger Dirk,
Roth Johannes,
Janssens Hein J. E. M.,
Merriman Tony R.,
Broen Jasper C. A.,
Janssen Matthijs,
Radstake Timothy R. D. J.
Publication year - 2015
Publication title -
arthritis and rheumatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.106
H-Index - 314
eISSN - 2326-5205
pISSN - 2326-5191
DOI - 10.1002/art.39318
Subject(s) - medicine , gout , diabetes mellitus , proinflammatory cytokine , interleukin 8 , odds ratio , proteome , immunology , endocrinology , gastroenterology , inflammation , bioinformatics , biology
Objective 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. Methods 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‐8 (IL‐8)/CXCL8, IL‐1β, IL‐6, IL‐10, IL‐12, and tumor necrosis factor, after which we performed proteome‐wide 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‐related protein 8 (MRP‐8)/MRP‐14 complex. Results Compared to healthy controls and disease control patients, patients with gouty arthritis (n = 48) had significantly higher mean levels of CXCL8 ( P < 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 ( P < 0.0001). Proteome‐wide analysis in gouty arthritis (n = 18) and intercritical gout (n = 39) revealed MRP‐8 and MRP‐14 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 2 = 0.49, P < 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 2.8–96.6]) and CVD (odds ratio 3.9 [95% confidence interval 1.0–15.3]). Conclusion 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.