Diurnal variation of connective tissue metabolites in early and long-standing rheumatoid arthritis and in healthy individuals

Abstract

Objective:To study the circadian variability of circulating connective tissue metabolites in patients with very early (VERA) and long-standing rheumatoid arthritis (LRA) and in healthy control individuals.

Methods:Eleven patients with newly diagnosed, untreated RA, disease duration < 6 months, and 10 patients with LRA were included, together with 16 healthy control subjects. Seven blood samples were drawn serially from each participant at 3-hourly intervals from 10.00–22.00 h, fasting at 07.00 h the following day and finally at 10.00 h. Cartilage oligomeric matrix protein (COMP) and hyaluronan (HYA) were quantified by enzyme-linked immunosorbent assay (ELISA) and the N-terminal propeptide of collagen type III (PIIINP) was determined by radioimmunoassay (RIA).

Results: The two RA subsets did not differ with respect to age, gender distribution, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), immunoglobulin M rheumatoid factor (IgM-RF) status, global health status and pain. Healthy controls were younger than both VERA and LRA patients. At baseline, PIIINP, HYA, and COMP were increased significantly in both RA cohorts compared with controls. No circadian rhythmicity was recorded with respect to HYA and PIIINP. By contrast, COMP was decreased at 07.00 h in all three study groups; this decline was particularly prominent in LRA.

Conclusion:Within-day changes of PIIINP, HYA, and COMP are qualitatively similar in RA at different stages and in healthy individuals, indicating that the connective tissue responses to rhythmic physiological signals are not abolished by disease-modifying anti-rheumatic drug (DMARD) therapy. Serum for measurement of HYA and COMP should be collected between 10.00 and 20.00 h.

Acknowledgements

This study was investigator initiated. It was supported by the Danish Rheumatism Association, the Institute of Clinical Research at the University of Southern Denmark, and the Foundation for Regional Research in the County of Southern Jutland. The expert technical contribution by Kirsten Junker is greatly appreciated.