Immunopathogenesis of Granulomas in Chronic Inflammatory Diseases : Relevance to diagnostics, biomarkers and treatment

Granulomas are formed in chronic immune mediated diseases such as sarcoidosis and Crohn’s disease as a sign of chronic inflammation. These diseases present with different clinical features, yet overlap in treatment and possibly immunopathogenesis. In this thesis we studied the involvement of B cells in Crohn’s disease in peripheral blood and inflamed intestinal tissue. As B cells showed to be numerously present in granulomatous tissue we analyzed whether additional B-cell staining would lead to an increase in granuloma detection in patients with Crohn’s disease. The effect of infliximab on B-and T-cell subsets was studied in patients with sarcoidosis before and during therapy in order to find immunological markers predicting therapeutic success. Furthermore, the effect of infliximab in patients with neurosarcoidosis was described in a multicenter cohort. With this thesis, we provide new evidence for the involvement of B cells in the immunopathogenesis of granulomatous inflammatory diseases. This opens new targeted treatment options for these disorders, by either targeting B cells or through B-T cell interactions.