In:
Arthritis & Rheumatology, Wiley, Vol. 67, No. 12 ( 2015-12), p. 3303-3313
Abstract:
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.
Type of Medium:
Online Resource
ISSN:
2326-5191
,
2326-5205
Language:
English
Publisher:
Wiley
Publication Date:
2015
detail.hit.zdb_id:
2754614-7
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