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P166 IDENTIFYING A GENE EXPRESSION SIGNATURE FOR PROGRESSIVE PULMONARY SARCOIDOSIS
1N Kulakova, 2D Baban, 3A Leonard, 2J Taylor, 1AJ McMichael, 1L-P Ho. 1MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, Oxford, UK, 2Wellcome Trust Centre for Human Genetics, Oxford University, Oxford, UK, 3Conquest Hospital, St Leonard’s-on-Sea, UK
In recent years, DNA microarray technology has progressed from a means of identifying potential genes involved in disease causation to a technique that can be used to find subclasses in disease states and identify biological markers associated with disease outcome. In sarcoidosis, one of the key questions in clinical management is which subset of patients will progress to chronic disease and whether treatment in this group of patient will alter the natural history of the disease. There are currently no markers that can be applied at disease presentation to identify patients at risk of disease progression. It is thus also not possible to assess whether early treatment will improve outcome in this group. We question if a global gene expression pattern in the lungs might predict the subset of patients with pulmonary sarcoidosis that progresses to chronic disease. We hypothesise that in patients with progressive pulmonary sarcoidosis, a different set of genes are activated to drive the route of inflammation towards that of a fibrotic pathway. In the first part of the study, we examine the viability of gene profiling of RNA obtained from bronchoscopic transbronchial biopsies and if differences in gene expression pattern can be observed in the lungs from biopsy-confirmed sarcoid patients with asymptomatic disease and Scadding stage 1–2 chest x ray (CXR) changes compared with patients with persistent symptoms, Scadding stage 2–3 CXR changes and abnormal pulmonary function test (n = 8 patients, non-smokers, no treatment, excluding Loefgren’s syndrome, matched for gender and age). Labelled complementary RNA was hybridised to …
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