Sleep Disturbances are a Significant Predictor of Chikungunya Arthritis Flare Severity.

Sarah R Tritsch ,Dennys Jiménez ,Karol Suchowiecki,Alberto David Cabana Jimenez ,Christopher N Mores ,Gary S Firestein ,Richard L Amdur ,Evelyn Mendoza-Torres,Carlos Alberto Perez Hernandez ,Gary L Simon ,Wendy Rosales,Liliana Encinales,Paula Bruges Silvera,Paige Fierbaugh,Jennifer Carolina Martinez Zapata ,Andrés Cadena ,Carlos Andres Herrera Gomez,Yerlenis Galvis Crespo,Geraldine Avendaño,Alfonso Sucerquia Hernandez,Aileen Y Chang

doi:10.33696/immunology.3.098

Abstract

Objective:The primary objective of this research was to explore the link between sleep and flare pain associated with chikungunya virus (CHIKV) infection. The secondary objective was to investigate if cytokines and T regulatory (Treg) cells have an influence on this relationship.Methods:A cross-sectional study was performed using data collected in Barranquilla, Colombia, which enrolled patients with and without chronic arthritis with a history of chikungunya infection. Flare severity was measured by a version of the Outcome Measures in Rheumatoid Arthritis Clinical Trials (OMERACT) flare questionnaire adapted for CHIKV arthritis, including metrics for pain, difficulty with physical activity, fatigue, stiffness and difficulty maintaining social activities due to arthritis that contribute to flare severity. In addition, four sleep disturbance items, five inflammatory cytokine levels, four anti-inflammatory cytokine levels, and six Treg levels were measured. Then, multivariable linear regression models were used to test the direct and indirect effects of flare-pain on sleep disturbance, and to determine whether this relationship was mediated by cytokines or Tregs. Finally, the SAS CALIS procedure was used to test path models showing possible causal effects with mediators and confounds.Results:The analysis showed that sleep disturbance is positively correlated with CHIKV arthritis flare pain, and that it is a significant predictor of flare severity after adjusting for demographic variables, cytokine, and T cell levels. Further, neither T cells nor cytokines mediate the pain/sleep relationship in CHIKV arthritis.Conclusion:There is a strong association between sleep disturbance and arthritis flare pain and severity; however, this relationship is not mediated by cytokines or T cells. Since this study is unable to determine causation, further research is needed to determine the mechanism underlying the relationship between sleep disturbances and CHIKV arthritis flares.

Highlights

Chikungunya virus (CHIKV) is an alphavirus transmitted by mosquitoes that causes debilitating arthritis
Inflammation was weakly affected by sleep disturbance, but has no effect on flare severity, so it did not act as a mediator here
Flare severity was a significant predictor of sleep disturbance (p

Summary

Introduction

Chikungunya virus (CHIKV) is an alphavirus transmitted by mosquitoes that causes debilitating arthritis. There are many similarities between post-CHIKV arthritis and rheumatoid arthritis (RA), including a higher incidence in older patients and in women, as well as relapsing-remitting symptoms including joint pain, swelling, and morning stiffness [1]. Chang et al found that low levels of IL-2, IL4, IL-13, and TNF-alpha during the acute phase of CHIKV infection was predictive of persistent joint pain [4]. Chow et al found an increased level of IL-6 was associated with persistent joint pain, while SepúlvedaDelgado et al suggested IL-6 could be used to predict CHIKV-induced arthritis due to the strong relationship between IL-6 levels in the acute phase and severity of joint involvement and delay in musculoskeletal symptom resolution [5,6]. C-reactive protein (CRP), an inflammatory marker used in the diagnosis of RA, is elevated during acute CHIKV infection [5]

Methods

Results

Discussion

Conclusion