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Title: A case control study of aetiological factors in primary achalasia
Author: Lau, Kar Wai
Awarding Body: Queen's University of Belfast
Current Institution: Queen's University Belfast
Date of Award: 2008
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Abstract:
Primary achalasia is the best characterized oesophageal motor disorder but the aetiology is unknown. Based on current evidence, autoimmune, infectious and genetic factors may be involved in the pathogenesis of the condition. One proposed pathophysiological mechanism for the condition is that an autoimmune reaction is induced in genetically susceptible individuals by one or a combination of environmentall infectious agents. The aim of the study was to investigate potential risk factors, the role of the HSV-1 virus, HLA-DQB1 alleles and antineuronal antibodies in primary achalasia. Patients with primary achalasia and a control group were recruited for the study. In a study of risk factors for developing primary achalasia, a family history of nonachalasia! non- obstructive oesophageal swallowing disorders before age 60 and neurological disorders were associated with an increased risk. In addition, the following childhood factors also increased the likelihood of developing the condition: ch,ildhood passive smoking, use of an outdoor toilet, having a pet dog and a history of childhood hay fever. These findings would suggest that primary achalasia may have a multifactorial aetiology where both environmental and genetic factors are involved. Patients with primary achalasia have circulating T- lymphocytes that express HSV-1 specific receptors and exhibit a heightened cellular immunological response to HSV- 1 antigens. A higher proportion of cases also shed HSV-1 in saliva compared to controls. Seroprevalence of HSV-1 was high in patients with primary achalasia. These findings would support a role for HSV-1 in the pathogenesis of primary achalasia. The HLA-DQB1*0501 allele was identified as a risk allele in primary achalasia. Cases possessing this allele demonstrated a higher magnitude of cellular immunity to HSV- 1 as compared to cases without the allele. These findings support the role of an immunogenetic predisposition for the development of primary achalasia.
Supervisor: Not available Sponsor: Not available
Qualification Name: M.D.--Queen's University of Belfast, 2008 Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.491710  DOI: Not available
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