[2008] [THU0361] CHRONIC FATIGUE SYNDROME PATIENTS HAVE SERUM N-GLYCOSYLATION CHANGES WHICH MAY REFLECT DOLICHOL DYSFUNCTION

J.S. Axford1, O. Fraser1, A. Alavi1, E. Tarelli2, J. Kerr1. 1Cellular and Molecular Medicine; 2Medical Biomics Centre, St George's University London, London, United Kingdom

Background: Chronic fatigue syndrome (CFS) is characterised by a severe debilitating fatigue lasting for at least 6 consecutive months as well as numerous other muscular, infectious and neuropsychiatric symptoms and sleep disturbances. CFS is thought to have a worldwide prevalence of 0.4–1% with approximately 240,000 patients in the UK. Diagnosis is based on clinical criteria and critically depends on exclusion of other physical and psychiatric diseases. Studies of pathogenesis have revealed immune system abnormalities and chronic immune activation, dysfunction of the hypothalamic–pituitary–adrenal (HPA) axis, brain abnormalities and evidence of exogenous insults, for example, various microbial infections (Epstein-Barr virus, enteroviruses, parvovirus B19, Coxiella burnetii and Chlamydia pneumoniae), vaccinations and exposure to organophosphate chemicals and other toxins (Papanicolaou et al., 2004). A report on isoprenoid pathway dysfunction in CFS (Kurup & Kurup, 2003) showed that there was an increase in dolichol levels, carbohydrate residues of glycoproteins, glycolipids, total/individual glycosaminoglycans fractions and lysosomal enzymes in CFS.
Objectives: To analyse total serum N-glycosylation changes in CFS patients compared with healthy controls.
Methods: N-glycans were extracted from serum glycoproteins enzymically using PNGaseF, then isolated and purified on C18 and graphitized carbon SPE in tandem. The extracted serum N-glycans were analysed using High Performance Anion Exchange Chromatography – Pulse Amperometric Detection (HPAEC-PAD) and Matrix Assisted Laser Desorption/Ionisation Time of Flight Mass Spectrometry (MALDI-TOF MS).
Results: N-Glycosylation differences were observed when comparing CFS serum (n=20) those obtained from healthy controls (n=20). There was a decrease in the relative percentage of agalactosylated (p=0.016) and monogalactosylated (p=0.016) structures, and an increase in the percentage of monosialylated (p=0.0002) and disialylated (p=0.006) when comparing the total serum N-glycans from CFS patients to healthy controls.
Conclusion: There are obvious differences in N-glycosylation of serum glycoproteins in CFS patients. These differences may be related to the altered levels of dolichol (which is vitally important for N-glycosylation of proteins and protein processing) observed in CFS patients. These N-glycosylation changes may be useful in identifying biomarkers to aid in CFS diagnosis as well as the development of treatment monitoring of CFS.
References: Papanicolaou DA et al. Neuroimmunomodulation 2004;11(2):65–74.
Kurup KK et al. Acta Neuropsychiatrica 2003: 15:266–273

Ann Rheum Dis 2008;67(Suppl II):250

Session: Fibromyalgia

 

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