Mohammad Isa, H; (2015) Predictors of Disease Extension and Progression in Patients with Granulomatosis with Polyangiitis (GPA). Doctoral thesis , UCL (University College London).

PDF Hazlita Mohammad Isa COMPILATION (FINAL FOR UCL SUBMISSION).pdf Available under License : See the attached licence file. Download (17MB)

Abstract

Granulomatosis with Polyangiitis (GPA) is a granulomatous inflammatory disease. It is generally described as a systemic disorder which can present with a localized presentation like the orbit. Orbital GPA can be the initial manifestation of GPA where over time the disease may progress and become severe, involving vital organs. This study aimed to look for biomarkers in orbital GPA biopsies that could indicate diagnosis and be a predictor for the progression of the disease. To identify GPA patients, retrospective examination of patients’ medical records, who had undergone orbital biopsies for orbital inflammatory disease (OID), over a 21 year period, was performed. Long term outcomes of these patients were studied. Further subjective and objective histology analyses were done on haemotoxylin and eosin (H&E) tissue preparations. Comparison of cellular activity in biopsies of GPA and other OID were performed. Further T cells, B cells and macrophage phenotypes and their cytokines, were investigated with immunohistochemistry (IHC). IHC cell count comparisons were performed between GPA, sarcoidosis and idiopathic inflammatory orbital diseases (IIOD) biopsies. Results showed that in patients who presented with orbital GPA with no systemic manifestations, the disease remained localised and did not progress to systemic form, over time. H&E tissue biopsies examination showed that GPA tissues had a higher cellular activity compared to OIDs. Vasculitis and necrosis were found to be independently associated with the diagnosis of orbital GPA but these features were unreliable for diagnosis as a number of the biopsies did not exhibit these features. In immunohistochemistry staining, T cells, B cells and macrophage subtypes counts were comparable between GPA, sarcoidosis and IIOD. Nonetheless cytokines IL-17, IL-23 and BAFF-receptor (BAFF-R), were found significantly more in GPA compared to sarcoidosis and IIOD. This suggests that these cytokines possibly have a role in the pathogenesis of GPA and may have diagnostic value.

Download activity - last month

Export as XMLCSVJSON

Download activity - last 12 months

Export as JSONCSVXML

Downloads by country - last 12 months

Export as JSONXMLCSV

Archive Staff Only

View Item