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

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


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.

MeSH terms

  • Adult
  • Arthritis, Rheumatoid / blood
  • Arthritis, Rheumatoid / complications*
  • Arthritis, Rheumatoid / physiopathology
  • Autoantibodies / blood
  • Autoimmune Diseases / complications
  • Autoimmune Diseases / physiopathology
  • Biomarkers / blood
  • Cardiovascular Diseases / blood
  • Cardiovascular Diseases / complications*
  • Cardiovascular Diseases / diagnosis
  • Case-Control Studies
  • Cohort Studies
  • Fatty Acids, Nonesterified / blood*
  • Female
  • Hormones / blood*
  • Humans
  • Male
  • Middle Aged
  • Norepinephrine / blood
  • Peptides / blood*
  • Peptides / metabolism
  • Peptides, Cyclic / immunology
  • Risk Factors
  • Triglycerides / blood


  • Autoantibodies
  • Biomarkers
  • Fatty Acids, Nonesterified
  • Hormones
  • Peptides
  • Peptides, Cyclic
  • Triglycerides
  • Norepinephrine