The Potential of Circadian Realignment in Rheumatoid Arthritis

Rao, Rohit; Pierre, Kamau; Schlesinger, Naomi; Androulakis, Ioannis P.

doi:10.1615/critrevbiomedeng.2016018812

Cited by 16 publications

(11 citation statements)

References 125 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…One way to induce a delay of this kind would be through light exposure in the evening [ 16 ]. Rao et al [ 17 ] elaborate extensively on the promising role of circadian realignment in improving RA outcomes.…”

Section: Discussionmentioning

confidence: 99%

Earlier chronotype in patients with rheumatoid arthritis

et al. 2021

View full text Add to dashboard Cite

Objectives Rheumatoid arthritis (RA) patients show an earlier circadian rhythm (i.e. serum melatonin peaks earlier during the night, indicating an earlier timing of the internal circadian pacemaker). In the current study, we examined whether the chronotype, which is influenced by the circadian rhythm, is also earlier. In addition, we explored whether chronotype is related to disease activity and patient-reported outcomes. Methods The chronotype (Munich Chronotype Questionnaire) of patients with RA (n = 121; mean age 60 years, 73% female) was compared with that of subjects from the general population (norm group; n = 1695) with a one-sample t test. In addition, we investigated chronotype in relation to disease activity (Disease Activity Score; DAS), reported morning stiffness, fatigue (Checklist Individual Strength), and health-related quality of life (RAND-36). Results The chronotype of patients with RA was, on average, 23 min (95% CI, 15 to 31 min) earlier than that of the norm group (t(115) = − 5.901, p < 0.001, d = 0.55). Chronotype was not related to disease activity or patient-reported outcomes (p > 0.05). Conclusion As expected, chronotype was earlier in RA patients. However, in this correlational study, chronotype was not related to disease activity or patient-reported outcomes. An experimental study is needed to examine whether delaying the circadian rhythm has a positive influence on these outcomes. This insight could improve our understanding of the pathophysiology of RA and contribute to exploring new treatment possibilities. Key Points• This is the first study examining chronotype in patients with rheumatoid arthritis, and how chronotype relates to disease activity and patient-reported outcomes.• We found an earlier chronotype in patients with rheumatoid arthritis than in subjects from the general population.• In this correlational study, chronotype was not related to disease activity or patient-reported outcomes. An experimental study is needed to examine whether delaying the circadian rhythm positively influences these outcomes.

show abstract

Section: Discussionmentioning

confidence: 99%

Earlier chronotype in patients with rheumatoid arthritis

et al. 2021

View full text Add to dashboard Cite

show abstract

“…The impact of season on vitamin D levels is well-known 3,4 Similarly, season impacts the incidence and course of RA [19][20][21] , likely owing to circadian rhythms affecting pro-inflammatory cytokines 22,23 . This may be explained by effects of seasonal changes in vitamin D affecting the immune system 24 , perhaps through seasonal impact on relevant genes, independent of vitamin D metabolism 25,26 .…”

Section: Discussionmentioning

confidence: 99%

Impact of season on the association between vitamin D levels at diagnosis and one-year remission in early Rheumatoid Arthritis

Herly

Stengaard‐Pedersen

Vestergaard

et al. 2020

Sci Rep

View full text Add to dashboard Cite

the study evaluates associations between serum vitamin D metabolites at diagnosis and one-year remission, in early diagnosed rheumatoid arthritis(RA). The CIMESTRA-cohort comprised 160 newly diagnosed RA patients, treated aiming at remission. Vitamin D supplementation was recommended according to national guidelines. D total (25OHD 2 + 25OHD 3) was dichotomized at 50 nmol/L, 1,25(OH) 2 D was categorized in tertiles. Primary outcome was remission(DAS28-CRP ≤ 2.6) after one year. Associations were evaluated using logistic regression, further adjusted for pre-specified potential confounders: Age, sex, symptom-duration before diagnosis, DAS28-CRP and season of diagnosis. Results are presented as Odds Ratios(OR) with 95% Confidence Intervals(95%CIs). In univariate analyses, neither D total nor 1,25(OH) 2 D were associated with remission. In adjusted analyses, low D total was associated with higher odds for remission; OR 2.6, 95%CI (1.1; 5.9) p = 0.03, with season impacting results the most. one-year remission was lower in patients with diagnosis established at winter. in conclusion, low D total at diagnosis was associated with increased probability of achieving one-year remission in early RA when adjusting for covariates. Diagnosis in winter was associated with lower odds for one-year remission. Results suggest that season act as a contextual factor potentially confounding associations between vitamin D and RA disease-course. The finding of low D total being associated with higher one-year remission remains speculative. Mounting evidence suggests vitamin D as an important immune-modulator 1,2. Circulating 25OHD 3 is produced in the skin upon sun-exposure, dependent on e.g. season and latitude 3 , and circannual variation in 25OHD is well-known in Northern latitude 4. 25OHD serves as substrate for conversion into the active metabolite; 1,25(OH) 2 D, both in the kidneys 3 and locally in macrophages, dendritic cells and lymphocytes 5. Immunomodulation by sufficient levels of 1,25(OH) 2 D includes altered differentiation and maturation of dendritic cells, macrophages and lymphocytes 5 , and inhibition of pro-inflammatory cytokines 6. The main-effect of vitamin D on the immune system is to balance the immune-response away from the self-aggressive Th1/ Th17-response and towards the tolerogenic Th2/Th-regulatory response 7,8 .

show abstract

“…However, this had not a significant impact on disease incidence, score, and paw thickness. Regarding the therapeutics of RA based on circadian knowledge, the realignment of the circadian rhythms of immune mediators and chronotherapy might lead to the improvement of RA symptoms (Cutolo, 2016; Rao et al, 2016).…”

Section: Circadian Rhythm Associated Diseasesmentioning

confidence: 99%

Circadian rhythm and disease: Relationship, new insights, and future perspectives

Neves

Albuquerque

Quintela

et al. 2022

Journal Cellular Physiology

View full text Add to dashboard Cite

The circadian system is responsible for internal functions and regulation of the organism according to environmental cues (zeitgebers). Circadian rhythm dysregulation or chronodisruption has been associated with several diseases, from mental to autoimmune diseases, and with life quality change. Following this, some therapies have been developed to correct circadian misalignments, such as light therapy and chronobiotics. In this manuscript, we describe the circadian‐related diseases so far investigated, and studies reporting relevant data on this topic, evidencing this relationship, are included. Despite the actual limitations in published work, there is clear evidence of the correlation between circadian rhythm dysregulation and disease origin/development, and, in this way, clock‐related therapies emerge as great progress in the clinical field. Future improvements in such interventions can lead to the development of successful chronotherapy strategies, deeply contributing to enhanced therapeutic outcomes.

show abstract

The Potential of Circadian Realignment in Rheumatoid Arthritis

Cited by 16 publications

References 125 publications

Earlier chronotype in patients with rheumatoid arthritis

Earlier chronotype in patients with rheumatoid arthritis

Impact of season on the association between vitamin D levels at diagnosis and one-year remission in early Rheumatoid Arthritis

Circadian rhythm and disease: Relationship, new insights, and future perspectives

Contact Info

Product

Resources

About