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Circadian rhythms of cellular immunity in rheumatoid arthritis: a hypothesis-generating study.
- Source :
-
Clinical and experimental rheumatology [Clin Exp Rheumatol] 2015 Jan-Feb; Vol. 33 (1), pp. 34-43. Date of Electronic Publication: 2014 Dec 22. - Publication Year :
- 2015
-
Abstract
- Objectives: The circadian rhythm of clinical symptoms in rheumatoid arthritis (RA) has been primarily attributed to circadian variations in humoral factors and hormones. In this study, we investigated circadian rhythms of cellular immunity in RA (CiRA study).<br />Methods: Peripheral blood of female postmenopausal patients with active RA (DAS 28 ≥ 4.2) (n=5) and female postmenopausal non-RA controls (n=5) was collected every 2 hours for 24 hours and analysed by flow cytometry, cytokine multiplex suspension array and quantitative RT-PCR of clock gene expression in isolated CD14+ monocytes. Endogenous circadian rhythms of macrophages were investigated by BMAL1-luciferase bioluminescence. Significance of circadian rhythms was tested by Cosinor analysis.<br />Results: We found (i) circadian rhythms in the relative frequency of peripheral blood cell populations that were present in postmenopausal non-RA controls but absent in patients with active RA, (ii) circadian rhythms that were absent in non-RA controls but present in patients with RA and (iii) circadian rhythms that were present in both groups but with differences in peak phase or amplitude or amplitude/magnitude. The circadian rhythm in expression of the clock genes PER2 and PER3 in CD14+ monocytes was lost in patients with RA. The amplitude of BMAL1-luciferase bioluminescence tended to be lower in patients with RA than in non-RA controls.<br />Conclusions: We conclude that (i) in RA some immune cell populations lose their normal circadian rhythms whereas others establish new 'inflammatory' circadian rhythms and (ii) these findings provide a good basis for further identifying pathophysiological aspects of RA chronobiology with potential therapeutic implications.
- Subjects :
- Adaptation, Physiological
Aged
Arthritis, Rheumatoid blood
Arthritis, Rheumatoid genetics
Arthritis, Rheumatoid physiopathology
Biomarkers blood
Case-Control Studies
Cytokines blood
Female
Humans
Immunity, Humoral
Inflammation Mediators blood
Lipopolysaccharide Receptors blood
Macrophages metabolism
Middle Aged
Monocytes metabolism
Period Circadian Proteins genetics
Pilot Projects
Postmenopause immunology
RNA, Messenger blood
Time Factors
Arthritis, Rheumatoid immunology
Circadian Rhythm genetics
Immunity, Cellular
Macrophages immunology
Monocytes immunology
Subjects
Details
- Language :
- English
- ISSN :
- 0392-856X
- Volume :
- 33
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Clinical and experimental rheumatology
- Publication Type :
- Academic Journal
- Accession number :
- 25535886