Hormone, metabolic peptide, and nutrient levels in the earliest phases of rheumatoid arthritis\u2014contribution of free fatty acids to an increased cardiovascular risk during very early disease

Man Wai Tang,Jan P.M Visscher,Paul Peter Tak,Maria J De Hair,Frieda A Koopman,Danielle M Gerlag

doi:10.1007/s10067-016-3456-x

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.

Highlights

Rheumatoid arthritis (RA) is a chronic autoimmune disease affecting approximately 1 % of the population worldwide
Healthy controls were matched for age with the at-risk individuals rather than the RA patients, because on average age is higher in RA patients than in at-risk individuals
The results presented here show the levels of hormones and metabolic peptides in a cohort of individuals at risk of developing RA, patients with established RA, and healthy controls

Summary

Introduction

Rheumatoid arthritis (RA) is a chronic autoimmune disease affecting approximately 1 % of the population worldwide. Twenty-two patients with active RA, 45 individuals at risk for developing RA, and 16 healthy controls were included in the first part of this study. The individuals at risk for RA had arthralgia and/or a positive family history for RA, without any evidence of arthritis upon thorough physical examination They were positive for IgM rheumatoid factor (IgM-RF) and/or anticitrullinated protein antibodies (ACPAs). We included an independent validation cohort, consisting of 32 individuals at risk for RA (arthralgia and elevated IgM-RF and/or ACPA serum levels without clinically manifest arthritis), 20 early arthritis patients with disease duration

Results

Discussion

Compliance with ethical standards