Identification of trigger-related phenotypes in sarcoidosis

Abstract

Sarcoidosis is a systemic disease characterized by the formation of non-caseating granulomas. Virtually any organ can be affected and its course is unpredictable. The heterogeneous presentation together with the fact that various antigens, including certain bacteria and inorganic agents, are able to stimulate granuloma formation, makes it plausible that multiple antigens are able to trigger sarcoidosis. This thesis addresses the question whether potential triggers relate to a different presentation or disease course in sarcoidosis: trigger-related sarcoidosis phenotypes. Although no difference was observed between sarcoidosis patients and controls in immunological sensitization towards bacterial and auto-antigens, significant more sarcoidosis patients showed sensitization to metals and silica, which was associated with development of pulmonary fibrosis. We observed a surprising association between cardiac involvement and sensitization to mycobacterial antigens. We also showed that C. acnes could be detected in granulomas of a subgroup of patients with sarcoidosis which was associated with a chronic disease phenotype. Interestingly, we found presence of C. acnes in granulomas of patients with other granulomatosis diseases as well. The role of C. acnes as a specific antigenic trigger in sarcoidosis could therefore be questioned. It is possible that C. acnes is not a specific trigger of sarcoidosis, but that it contributes to granuloma formation and maintenance in a more mitogenic way. The results of this thesis strengthen the hypothesis that trigger-related phenotypes do exist in sarcoidosis. Identification of trigger-related phenotypes may make disease prognosis more predictable and make it possible to explore a more personalized based treatment regime in subgroups of patients.