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A study of the immunology, virology and therapy of the chronic fatigue syndrome

Hassan, Imad Salah Ahmed; (1999) A study of the immunology, virology and therapy of the chronic fatigue syndrome. Doctoral thesis (M.D), UCL (University College London). Green open access

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CFS is a chronic debilitating illness characterised by undue physical and mental fatigue and fatigueability, alterations of mood and recurrent low-grade fever, pharyngitis, lymphadenopathy, myalgia, arthralgia and sleep disturbance. Depression and cognitive dysfunction are the two other facets of CFS. Incidence in the UK is estimated to be around 1.3/1000 of the population. CFS causes considerable human suffering and poses a substantial economic burden on both patients and health providers. The illness is generally thought to be multiaetiologic in origin. An immunologic dysfunction associated with a persistent or reactivated viral infection is believed to be one principle aetiopathogenic mechanism. In a small, open-labelled, randomised study interferon-alpha was effective in improving the functional abilities in a subset of patients who were Coxsackie immunoglobulin M-positive (IgM). In this open- labelled, cross-over study we attempted to substantiate the latter finding and also investigate the functional, psychiatric and immunologic dysfunction in these patients and their relationship to improvement. 48 adult patients satisfying the Oxford criteria were enrolled of whom 25 received immediate treatment and 23 after a three months period of observation. As more specific ELISA tests for enterovirus IgM antibodies became available, all patients tested negative and the relationship of this antibody to outcome could not be retested. Using the Short Form-36 (SF-36) which measures eight aspects of patient's physical and emotional well-being and the general health questionnaire (GHQ) as a specific gauge of psychological health we substantiated the severe impact of the illness on all aspects of physical and psychological health in sufferers. Immunologically, there was evidence of both immunoactivation as suggested by the significantly increased relative expression of class II antigens in CD4 and CDS cells and reduced CD28 expression on CDS cells and of increased expression of the apoptosis repressor complex bcl-2 and bcl-2/bax in both CD4 and CDS cells. Additionally, lower (worse) SF-36 scores correlated with higher (worse) GHQ scores and class II antigen expression and lower CD28 display on CDS cells. Similarly, those with worse GHQ, mental and emotional health scores had lower phytohemagglutinin (PHA) proliferative responses. The former findings attest to a probable unifying mechanism causing both immune dysfunction and clinical morbidity while the latter findings have a bearing on a neuroimmune 'cross-talk'. None of the patients improved significantly during observation without treatment. At six months post-therapy, of 33 patients who completed a course of 3-6 million units of interferon alpha for 12 weeks, 14 rated themselves as improved. Of the latter, six rated themselves as much improved. On an 'intention to treat' basis, this represents 14 out of 48 recruited (29.2%). Improvement was gradual and stepwise, usually noticed by patients within three months of stopping interferon alpha. Improvement was associated with a similar trend in clinical, functional and psychological impairments. More importantly, improvers had lower CD28 and PHA proliferative responses at baseline, the increase of which with treatment mirrored the improvement in the SF-36 and GHQ. As the abnormalities in these two immune parameters might be related to a viral infection, improvement with treatment could be related to an interferon-antiviral effect.

Type: Thesis (Doctoral)
Qualification: M.D
Title: A study of the immunology, virology and therapy of the chronic fatigue syndrome
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Thesis digitised by ProQuest.
Keywords: Health and environmental sciences; Chronic fatigue syndrome
URI: https://discovery.ucl.ac.uk/id/eprint/10121238
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