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Title: Genetics and genomics in autoimmune disease and healthy individuals
Author: Carr, E. J.
Awarding Body: University of Cambridge
Current Institution: University of Cambridge
Date of Award: 2011
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To look for common genetic variants associated with systemic lupus erythematosus (SLE) and anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) we genotyped 11 loci previously associated with T1D and containing regulators of the immune response. CTLA4 and PTPN22 were found to be associated with AAV. IL2RA was a susceptibility locus for both AAV and SLE. The association of each disease with the IL2RA region is complex. T1D associated independently with 3 single nucleotide polymorphisms (SNPs), whereas AAV and SLE were each associated with a different one of the three T1D-associated SNPs. The IL2RA region is also a known susceptibility locus for multiple sclerosis (MS) and Graves’ disease. Transcriptional profiling of purified CD8 T cells has previously identified two distinct patient subgroups in both AAV and SLE. The patients from one subgroup (8.1) had significantly more frequency relapses and a significantly larger CD8 T cell memory compartment than the other subgroup (8.2). We looked for the presence of these subgroups in MS, along with their ability to predict conversion from clinically isolated syndrome to MS. We tested for an HLA association and for an association with cytomegalovirus and Epstein-Barr virus infection. Two analogous subgroups (c8.1 and c8.2) were identifiable in the healthy population. A study testing for association between c8.1 and c8.2 and vaccine response was conducted using both T-dependent and T-independent vaccines to S. pneumoniae. Antibody titres to some serotypes of S. pneumoniae were associated with CD8 T cell subgroup at a single time point. Intriguingly, this study demonstrated that healthy individuals were able to change from c8.1 to c8.2 and vice versa after vaccination with either vaccine.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available