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. 2017 Feb;36(2):269-278.
doi: 10.1007/s10067-016-3456-x. Epub 2016 Nov 2.

Hormone, metabolic peptide, and nutrient levels in the earliest phases of rheumatoid arthritis-contribution of free fatty acids to an increased cardiovascular risk during very early disease

Man Wai Tang  1   2 , Frieda A Koopman  1 , Jan P M Visscher  1 , Maria J de Hair  1 , Danielle M Gerlag  1   3 , Paul Peter Tak  4   5   6   7
Affiliations

Hormone, metabolic peptide, and nutrient levels in the earliest phases of rheumatoid arthritis-contribution of free fatty acids to an increased cardiovascular risk during very early disease

Man Wai Tang et al. Clin Rheumatol. 2017 Feb.

Abstract

Rheumatoid arthritis (RA) is a chronic autoimmune disease associated with changes in several hormones and metabolic peptides. Crosstalk between these factors and the immune system may be important for homeostasis during inflammation. Here, we studied the levels of hormones, metabolic peptides, and nutrients in individuals at risk for developing RA (at risk). In total, 18 hormones, metabolic peptides, and nutrients were measured in fasting serum samples from 45 autoantibody-positive individuals at risk, 22 RA patients, and 16 healthy subjects. Triglyceride (TG) levels were also measured in an independent validation cohort of 32 individuals at risk, 20 early arthritis patients, and 20 healthy controls. We found an elevated TG level in individuals at risk and significantly higher TG levels in RA patients compared to healthy controls. These results were confirmed in the validation cohort. Similarly, free fatty acid (FFA) levels showed an increase in individuals at risk and were significantly higher in RA patients compared to healthy controls. In RA patients, FFA levels were positively correlated with disease activity. Pancreatic polypeptide (PP) and norepinephrine levels were highly significantly increased in individuals at risk and RA patients compared to healthy controls. TG and FFA levels are increased in RA patients and positively correlated with disease activity parameters. The results presented here suggest a role for FFAs in the pathogenesis of RA. Furthermore, PP and norepinephrine may be a biomarker that could assist in the identification of individuals at risk.

Keywords: Autoantibodies; Biomarkers; Cardiovascular disease; Clinical trials; Metabolic disease; Rheumatoid arthritis.

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Conflict of interest statement

Compliance with ethical standards Competing Interests All authors do not have financial or other relationships that could give conflicts of interest. Dr. Gerlag and Professor Tak have become employees of GSK after completion of this study; GSK has not been involved in this study. Funding The study was supported by the European Union Seventh Framework Programme (project EuroTEAM; FP7-Health2–2012; grant number 305549). Authors’ Contributions All authors were involved in drafting the article or revising it critically for important intellectual content, and all authors approved the final version of the article to be published; agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. M.W.T contributed to research design, acquisition of data, and analyzed and interpreted data; F.A.K was involved in research design and acquisition of data; J.P.M.V. contributed to acquisition of data; M.J.H. was involved in analyzing and interpreting data; D.M.G designed the research and analyzed and interpreted data; P.P.T. designed the research and analyzed and interpreted data.

Figures

Fig. 1
Fig. 1
Hormones and peptides in healthy controls, at-risk individuals, and patients with RA. The serum a epinephrine, b norepinephrine, c adrenocorticotropic hormone (ACTH), d cortisol, e IL-6, f cortisol/IL-6 ratio, g estradiol, h follicle stimulating hormone (FSH), i luteinizing hormone (LH), (j) prolactin (PRL), k growth hormone (GH), l thyroid stimulating hormone (TSH), m triglycerides (TG), n free fatty acids (FFAs), o glucagon, p glucose, q insulin, and r pancreatic polypeptide (PP) level in healthy individuals, at-risk individuals, and patients with RA. One dot represents an individual and the median (interquartile range) is plotted as a line in the middle. Kruskal-Wallis test was used to detect differences in hormone levels between the groups. * P < 0.05028 (after Bonferroni correction)
Fig. 2
Fig. 2
The TG levels in healthy controls, at-risk individuals, and patients with early arthritis (validation cohort). a The serum TG levels were higher in at-risk individuals and patients with early arthritis compared to healthy controls. b The TG levels were significantly higher in at-risk individuals who developed arthritis compared to individuals who did not develop arthritis. One dot represents an individual and the median (interquartile range) is plotted as a line in the middle. Kruskal-Wallis or Mann-Whitney U test was used to detect differences in hormone levels between the groups. *P < 0.05
Fig. 3
Fig. 3
FFA level correlated moderately with several clinical and laboratory disease parameters in the RA patients. The correlations are shown between FFAs and a visual analog scale for global disease activity (VAS DA), b tender joint count 28 (TJC28), c swollen joint count 28 (SJC28), d erythrocyte sedimentation rate (ESR, mm/Hr), e C-reactive protein (CRP, mg/L) and disease activity score 28 (DAS28). One dot represents an individual. Spearman’s rank-order correlation coefficients were used to assess the correlations. * P < 0.05
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