Gene expression profile of CD4+ T lymphocytes from patients with eosinophilic granulomatosis with polyangiitis (EGPA) or Churg-Strauss syndrome

Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare and heterogeneous disease of unknown etiology, classified among ANCA-associated vasculitis, with an insatisfactory response to treatment. The aims of the current project are: 1) To investigate pathogenic pathways involved in EGPA that could be potentially druggable or provide clinically useful biomarkers by a cross-sectional study determining gene-expression profile of peripheral blood CD4+T lymphocytes in clinically stable patients with EGPA, patients with asthma and healthy controls. By using gene set expression analysis (GSEA) we will identify the main differentially expressed pathways. The most signficant differentially expressed transcripts will be validated as potential biomarkers by quantitative real time RT-PCR and by serum ELISA if encoding for a soluble product in an additional cohort. 2) To determine the heterogeneity of the EGPA by analyzing its transcriptome according to subgroups of patients defined by clinical variables and response to treatment. If we obtain significant differentially expressed genes for each category defined by clinical variables, these genes will be also validated in an additional cohort. 3) Moreover, an unsurpervised clustering analysis will be performed in order to identify non-predefined subtypes. With this study, we aim to contribute to the characterization of the molecular basis of the heterogeneity of EGPA patients and to identify pathways potentially involved in disease pathogenesis.