Use this URL to cite or link to this record in EThOS: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.744765
Title: An investigation of the relationship between exposure to inorganic and organic mercury and disease activity in systemic lupus erythematosus
Author: Crowe, William Mathew
ISNI:       0000 0004 7229 0342
Awarding Body: Ulster University
Current Institution: Ulster University
Date of Award: 2017
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Abstract:
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with an unknown aetiology. Strong evidence exists which suggests that the disease is initiated through a combination of genetic susceptibility and exposure to an environmental factor. One potential environmental factor is mercury (Hg) exposure, which is typically encountered in the form of inorganic mercury (iHg) and methylmercury (MeHg), primarily through dental amalgams and fish consumption, respectively. The effect of mercury exposure in existing autoimmune disease is unknown. The aim of this research was to investigate the role of iHg and MeHg exposure on disease activity and disease associated damage in SLE patients whilst controlling for confounding factors such as n-3 long chain polyunsaturated fatty acids (LCPUFA) and the genotype of genes associated with Hg metabolism (glutathione). This aim was achieved through the completion of observational studies in SLE cohorts based in Northern Ireland. Patients were assessed for Hg concentrations in their hair and urine and also underwent clinical assessment for three disease activity indices and one disease associated damage index. The first observational study (n=52) found a relationship between hair Hg and disease activity and disease associated damage. This finding was repeated in a second observational study (n=98); however, this relationship no longer existed when controlling for n-3 LCPUFA status, indicating that the inverse relationship between hair Hg and disease activity may be due to the concomitant consumption of n-3 LCPUFA present in fish. There was no relationship between urinary Hg or dental amalgams and disease activity or disease associated damage in either study. Neither of the single nucleotide polymorphisms (SNPs) of glutathione related genes investigated were predictors of hair Hg, urinary Hg, disease activity or disease associated damage. An ex vivo study was undertaken to investigate the differences in peripheral blood mononuclear cell (PBMCs) MeHg-induced inflammation between SLE patients and healthy controls and also to determine the impact of n-3 LCPUFA on the MeHg-induced inflammatory response. This study identified a significantly greater pro-inflammatory response from PBMCs of SLE patients (n=12) compared to that of age and sex matched controls (n=12) following ex vivo MeHg exposure. Furthermore, n-3 LCPUFA was shown to ameliorate MeHg induced cytokine release; however, this reduction was less pronounced in SLE patients. The results from this study suggest that SLE patients are more sensitive to MeHg-induced inflammatory response, and that the simultaneous exposure to n-3 LCPUFA is likely to mitigate the adverse effects of MeHg. Taken together, these data further support the evidence that suggests low level MeHg and iHg exposure appears to elicit no adverse effects in SLE patients and furthermore, the work described in this thesis suggests that n-3 LCPUFA is beneficial to SLE patients.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.744765  DOI: Not available
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