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

被引：82

作者：

Kienhorst, Laura B. E. ^{[1
]}

van Lochem, Ellen ^{[1
]}

Kievit, Wietske ^{[2
]}

Dalbeth, Nicola ^{[3
]}

Merriman, Marilyn E. ^{[4
]}

Phipps-Green, Amanda ^{[4
]}

Loof, Arnoud ^{[2
]}

van Heerde, Waander ^{[2
]}

Vermeulen, Sita ^{[2
]}

Stamp, Lisa K. ^{[5
]}

van Koolwijk, Elly ^{[1
]}

de Graaf, Jacqueline ^{[2
]}

Holzinger, Dirk ^{[6
]}

Roth, Johannes ^{[6
]}

Janssens, Hein J. E. M. ^{[1
,2
]}

Merriman, Tony R. ^{[4
]}

Broen, Jasper C. A. ^{[7
]}

Janssen, Matthijs ^{[1
]}

Radstake, Timothy R. D. J. ^{[7
]}

机构：

[1] Rijnstate Hosp, Arnhem, Netherlands

[2] Radboud Univ Nijmegen, Med Ctr, NL-6525 ED Nijmegen, Netherlands

[3] Univ Auckland, Auckland 1, New Zealand

[4] Univ Otago, Dunedin, New Zealand

[5] Univ Otago, Christchurch, New Zealand

[6] Univ Hosp Muenster, Munster, Germany

[7] Univ Med Ctr Utrecht, NL-3485 CX Utrecht, Netherlands

来源：

ARTHRITIS & RHEUMATOLOGY | 2015年 / 67卷 / 12期

基金：

欧洲研究理事会;

关键词：

URIC-ACID; NETTING NEUTROPHILS; GENE-EXPRESSION; RISK; MRP14; MORTALITY; ATHEROSCLEROSIS; IDENTIFICATION; EPIDEMIOLOGY; PREVALENCE;

D O I：

10.1002/art.39318

中图分类号：

R5 [内科学];

学科分类号：

100201 [内科学];

摘要：

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-1 beta, 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.

引用

页码：3303 / 3313

页数：11

共 49 条

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