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Title: The aetiology, pathogenesis and cellular origin of Hodgkin's disease
Author: Angel, Carole Ann
Awarding Body: University of Leicester
Current Institution: University of Leicester
Date of Award: 1998
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Hodgkin's disease (HD) is a lymphoproliferative disorder characterised by the presence of the Reed-Sternberg cell and its variants (HRS cells) in a polymorphic cellular background. Cure can now be achieved in more than 85% but the aetiology, pathogenesis and cellular origin have remained unclear despite extensive research. This thesis describes the results of histological, immunhistological and molecular biological studies of Hodgkin's disease. Previous immunohistological studies had suggested that one of the subtypes, nodular lymphocyte predominant HD, was a separate disease entity and was of B-cell origin. The results of this study instead suggest that all subtypes of the disease are derived from B-cells and that the different histological subtypes of the disease reflect differing host responses to the single pathogenetic process. Monoclonal B-cell proliferation was not identified by the molecular studies performed. It is likely that this reflects the relative insensitivity of the techniques used, since subsequent studies now indicate that most cases of NLPHD and a proportion of cases of classical HD are B-lymphoproliferative disorders. Finally, an aetiological role for EBV in a proportion of cases is suggested. When the results of these studies are analysed in the light of subsequent similar studies, a coherent hypothesis for the aetiology, pathogenesis and cellular origin of HD can be proposed. It is suggested that HD is a B-lymphoproliferative disorder arising when genetically predisposed individuals encounter particular environmental stimuli, one of which is EBV. This predisposition is currently poorly characterised but relates to defects in cellular immunity. Future studies should aim to characterise the underlying immune deficit, elucidate factors influencing progression, investigate aetiological agents in EBV-negative disease and assess the relevance of such findings to the prevention and management of Hodgkin's disease.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available