Article Text

Download PDFPDF

OP0312 A proteomic signature of fatigue in primary sjÖgren's syndrome
  1. R Omdal1,2,
  2. E Larssen3,4,
  3. C Brede5,
  4. A Hjelle4,
  5. AB Tjensvoll6,
  6. KB Norheim1,
  7. K Bårdsen4,
  8. K Jonsdottir7,
  9. P Ruoff8,
  10. MM Nilsen3,4
  1. 1Clinical Immunology Unit, Stavanger University Hospital, Stavanger
  2. 2Department of Medical Science, Faculty of Medicine and Science, University of Bergen, Bergen
  3. 3International Research Institute of Stavanger – IRIS
  4. 4Research Department
  5. 5Department of Medical Biochemistry
  6. 6Department of Neurology
  7. 7Department of Pathology, Stavanger University Hospital
  8. 8Centre for Organelle Research (CORE), University of Stavanger, Stavanger, Norway


Background Fatigue is a frequent and often disabling phenomenon in patients with chronic inflammatory and immunological diseases, neurodegenerative diseases, and cancer. The underlying biological mechanisms of fatigue are largely unknown and hypotheses are conflicting. It is important to uncover the pathophysiology and identify signalling pathways that generate and regulate this substantial phenomenon.

Objectives Based on the hypothesis that fatigue originates from cerebral processes, we investigated whether relevant proteins and/or signaling pathways for fatigue could be revealed in the cerebrospinal fluid (CSF) of patients with primary Sjögren's syndrome.

Methods Label-free shotgun mass spectrometry was performed to analyze the CSF proteome of 20 patients with primary Sjögren's syndrome. Fatigue was measured with the fatigue Visual Analogue Scale (fVAS).

Results After depletion of high-abundance proteins, more than 800 proteins were identified and quantitated. Multivariate analyses showed that patients with low and high fatigue could be separated based on their CSF protein profiles, and 15 proteins were selected as top discriminatory proteins. Among these were apolipoprotein A4, hemopexin, pigment epithelium derived factor, secretogranin-1, secretogranin-3, selenium-binding protein 1, and complement factor B.

The figure shows the top network from Ingenuity Pathway Analysis (IPA) with 14 of the differentially expressed proteins (red = upregulated, green = downregulated) and proteins that are directly associated to them (white molecules).

Conclusions Most of the discriminatory proteins have important roles in regulation of innate immunity, cellular stress defense, and/or functions in the central nervous system. Some have been associated with severe depression and loss of appetite, which are important features of chronic fatigue. These proteins and their interacting protein networks may therefore have central roles in the generation and regulation of fatigue, and the findings add new, relevant, and important evidence to the concept of fatigue as a biological phenomenon signaled through specific molecular pathways.


  1. Norheim KB, Jonsson G, Omdal R. Biological mechanisms of chronic fatigue. Rheumatology (Oxford). 2011;50:1009–18.

  2. Dantzer R, O'Connor JC, Freund GG, Johnson RW, Kelley KW. From inflammation to sickness and depression: when the immune system subjugates the brain. Nature reviews Neuroscience. 2008;9:46–56.

  3. Schutzer SE, Angel TE, Liu T, Schepmoes AA, Clauss TR, Adkins JN, et al. Distinct cerebrospinal fluid proteomes differentiate post-treatment lyme disease from chronic fatigue syndrome. PloS one. 2011;6:e17287.


Disclosure of Interest None declared

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.