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dc.contributor.authorDua, Priyamvada
dc.date.accessioned2015-09-15T14:12:17Z
dc.date.available2015-09-15T14:12:17Z
dc.date.issued2014
dc.identifier.citationDua, P. 2014. Functional effects of anti-neuronal antibodies in patients with encephalitis lethargica and related disorders associated with streptococcal infection. Queen Mary University of London.en_US
dc.identifier.urihttp://qmro.qmul.ac.uk/xmlui/handle/123456789/8704
dc.descriptionPhDen_US
dc.description.abstractEncephalitis lethargica affected a large number of people in the pandemic in the early 1900s (von Economo, 1930). Histological and biochemical data suggest that autoimmune mechanisms play an important role in this disorder and recently serum anti-basal ganglia antibodies (ABGA) have been detected in affected sporadic cases associated with evidence of recent streptococcal infection (Dale et al., 2004a). ABGA are also associated with other neuropsychiatric disorders including Sydenhams chorea, paediatric autoimmune neuropsychiatric disorders associated with streptococcal infections, Tourettes syndrome and obsessive compulsive disorder. The precise frequency, presentation, disease course, treatment response and causes of these disorders are still unknown. As ABGA are strongly associated with recent streptococcal infection, these disorders represent a potentially good model for the study of molecular mimicry and autoimmunity. The present study focussed on various aspects of this group of disorders. Profiling of group A streptococcus isolates from both patients with postulated post-streptococcal disorders of the CNS and controls was done which highlighted differences in virulence factors like M protein and superantigens between the two groups. Also in the present study we demonstrated the pathogenicity of anti-neuronal antibodies found in patients in both an in vivo and in vitro setting. An animal model of the disorders was produced by passive transfer of antibodies from patients which resulted in symptoms reminiscent of diseases like encephalitis lethargica and dystonia. An active immunization animal model using GABHS proteins and recombinant proteins (putative autoantigens) was also developed. Furthermore, the autoantibodies from patients and animal models were analysed on both neuronal and non-neuronal cells where they demonstrated to have a functional effect on cytotoxicity, apoptosis, calcium flux and enolase activity. N-methyl D-aspartate glutamate receptor and voltage gated potassium channel have been recently been implicated in a 16 range of neurological disorders, hence we also tested the patient sera for antibodies against these receptors and found a group of patients to be positive. In summary, EL and other ABGA-associated disorders are still an emerging entity, with major implications for neuropsychiatry. As auto-antibody mediated diseases respond to immunomodulatory therapy, identifying and defining the pathogenesis of these disorders is important so that patients can be appropriately treated.en_US
dc.description.sponsorshipThe Sophie Cameron Trust
dc.language.isoenen_US
dc.publisherQueen Mary University of London
dc.subjectGeographyen_US
dc.subjectMigrant Experienceen_US
dc.subjectMigrant enterpriseen_US
dc.titleFunctional effects of anti-neuronal antibodies in patients with encephalitis lethargica and related disorders associated with streptococcal infectionen_US
dc.typeThesisen_US
dc.rights.holderThe copyright of this thesis rests with the author and no quotation from it or information derived from it may be published without the prior written consent of the author


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