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Title: The potential pathogenicity of Dolosigranulum pigrum in multiple sclerosis, and the occurrence of the organism in the upper respiratory tract
Author: Jorge, Francis Mark
ISNI:       0000 0004 5352 3331
Awarding Body: University of Portsmouth
Current Institution: University of Portsmouth
Date of Award: 2014
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The bacterial toxins hypothesis in multiple sclerosis postulates that bacterial toxins from the human nasopharynx access the central nervous system and are implicated in the disease. Dolosigranulum pigrum was originally found in acute multiple sclerosis tissues. This study seeks to determine if the organism is found in human nasal tracts and explores the relationship between Dolosigranulum pigrum infection and multiple sclerosis by measuring antibody to the bacterium in multiple sclerosis patients and matched controls. Eighty eight clinical specimens were cultured onto blood agar and analysed using rabbit anti-Dolosigranulum pigrum sera, and fluorescein isothiocyanate. None tested positive for Dolosigranulum pigrum. Dolosigranulum pigrum was looked for using a novel polymerase chain reaction test. Thirty samples tested positive, 17 male, 13 female, with an age range from 8 days to 74 years. Twelve were sent for sequencing, seven matched Dolosigranulum pigrum, two showed mixed amplicons and three produced signals not matching Dolosigranulum pigrum. Sixty five multiple sclerosis sera and matched controls were tested for anti-Dolosigranulum pigrum using a novel enzyme linked immunosorbant assay. The multiple sclerosis group showed raised antibodies, significantly different to the controls, p ≤ 0.001. Fifteen of the multiple sclerosis sera and controls were Western blotted. There were no common bands when compared with rabbit sera containing antibodies to Dolosigranulum pigrum. This study shows that Dolosigranulum pigrum is found in the nasal tract. The elevated antibodies were not found to be anti-Dolosigranulum pigrum but their presence may be suggestive of bacterial products leaking from the nasal tract into the central nervous system. Further research into bacteria in the nasal tract is indicated. Introduction of markers into the nasal passages with subsequent tracking into the central nervous system by magnetic resonance imaging could provide evidence of a route by which bacterial molecules enter the central nervous system „behind‟ the blood brain barrier.
Supervisor: Mills, Graham ; Mernagh, Darren Sponsor: Not available
Qualification Name: Thesis (D.Biomed.Sci.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Biomedical Sciences