FRI0280 A molecular network for fatigue in primary sjÖgren's syndrome. (12th June 2018)

• Record Type: Journal Article
• Authors: Bårdsen, K.; Brede, C.; Kvivik, I.; Kvaløy, J.T.; Jonsdottir, K.; Tjensvoll, A.B.; Ruoff, P.; Omdal, R.
• Is Part Of: Annals of the rheumatic diseases. Volume 77(2018)Supplement 2
• Page Start: 678
• Page End: 678
• Publication Date: 2018-06-12
• Subjects: Rheumatism -- Periodicals; 616.723005
• DOI: 10.1136/annrheumdis-2018-eular.3656
• Languages: English
• ISSNs: 0003-4967

Abstract

Abstract : Background: Fatigue is a common phenomenon in primary Sjögren's syndrome (pSS) and other chronic inflammatory diseases, cancer, and neurodegeneration. The underlying mechanisms for fatigue are not completely understood, but increasing evidence point to a biological basis for the phenomenon. Objectives: Following the sickness behaviour hypothesis for fatigue, where pro-inflammatory cytokines and particularly interleukin 1β (IL-1β) related signalling are essential, we wished to investigate how molecules that influence IL-1β activity may influence fatigue through complex networks (IL-1β, IL-1Ra, IL-1RII, IL-6 and S100B). We also hypothesised that the neuropeptide hypocretin-1 (Hcrt1), a regulator of sleep and wakefulness, could be an element in a network for fatigue. Methods: In cerebrospinal fluid (CSF) from 49 patients with pSS, Hcrt1 was measured by RIA and the other proteins by ELISA. Fatigue was rated using the fatigue visual analogue scale (fVAS), and results analysed by univariate-, multiple regression, and principal component analysis (PCA). Results: It was not possible to measure IL-1b due to very low concentrations in CSF. In simple univariate regression analysis with fatigue as a dependent variable a significant association was observed for depression (R 2 =0.20, p<0.01), and pain (R 2 =0.23, p<0.01) and the biochemical variable IL-1Ra (R 2 =0.09, p=0.04). In multiple regression with fVAS as dependent variable a model was obtained with depression, pain, and IL-1Ra as significant contributors (R 2 =0.37; p<0.001). In PCA two significant components were revealed (figure 1a). The first component (PC1) was dominated by variables related to IL-1β activity. The second component (PC2) showed a negative correlation between IL-6 and Hcrt1. fVAS was then introduced as an additional variable. In this new model fVAS correlated with the IL-1β related variables on PC1 and to a lesser degree with Hcrt1 on PC2 (figure 1b). Conclusions: The main findings in this study indicate a functional network in which several IL-1β related molecules in CSF influence fatigue in addition to the clinical factors depression and pain. The neuropeptide Hcrt1 seem to participate in fatigue signalling, but probably not through the IL-1 pathway. Disclosure of Interest: None declared