IgG4-Related Disease: An Antigen Discovery Project

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IgG4-Related Disease: An Antigen Discovery Project

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Title: IgG4-Related Disease: An Antigen Discovery Project
Author: Washington, Cyrus G.
Citation: Washington, Cyrus G. 2016. IgG4-Related Disease: An Antigen Discovery Project. Master's thesis, Harvard Medical School.
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Abstract: IgG4 related disease is a multi-organ disease whose clinical manifestations often mimic infectious, malignant and inflammatory disorders. Prior to 2003, many well-defined eponyms were given to diseases whose causation was unknown. Further clinical investigations of these seemingly idiopathic diseases revealed many histopathological similarities. Originally identified in the pancreas as autoimmune sclerosing pancreatitis, the systemic characterization of the disease lends to its ability to present remarkably similar histopathological findings in distal locations. Clinically significant, and often shared, findings of the disease include storiform fibrosis, increased lymphoplasmacytic infiltrate rich in Igg4-positive plasma cells and tumefective lesions. Elevated Igg4 concentrations in serum have also been identified in some patients with IgG4-related disease, while a >40% IgG to IgG4 ratio is present in tissues. While a vignette of the pathophysiology has been loosely elucidated, the specific causative players are less characterized.

T cell studies of patients with IgG4 related diseases have implicated this subset of cells as a key player in the progression of the disease. Mechanistically, the role of T cells has been hypothesized not been clearly defined. GWAS studies of patients with Chrohn’s diseases identified a non-coding polymorphism at which the minor (G) allele is associated with a milder course of Chrohn’s disease. The identified SNP in the FOXO3A transcription factor was shown to limit inflammatory responses by the reduction of the pro-inflammatory cytokine TNFa by TGFB1, and the increase in the production of anti-inflammatory cytokines such as IL-10. Activated T-cells elicit their mechanisms of actions in a very polar like fashion. Therefore, in the context of IgG4 and the role of T-cells, studying the FOXO3 transcription may provide context to the role of these subset of cells in a patients with this disease. This antigen discovery project seeks to define a subset of antigens that are key in eliciting the activation of B cells in this disease. Furthermore, the identification of snps that lead to a milder prognosis may also help clarify the pathogenesis of IgG4 related disease.
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Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:33789919
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