Advances in understanding the immunopathology of sarcoidosis and implications on therapy

Abstract

Introduction: Sarcoidosis is a multi-systemic granulomatous disease of unknown aetiology. Ethnicity and environmental factors may influence disease incidence, phenotype and severity.

Areas covered: Predisposing genes are mainly involved in T cell and macrophage function, antigen presentation and recognition, and extra-cellular matrix turnover. No definitive relationship has been established with any proposed external trigger. A Th1/Th17-driven inflammatory process, involving macrophages both as antigen-presenting cells and key effectors, represent the main feature of the acute disease. Less is known about the determinants of clinical remission versus chronic disease and fibrosis. Treatment strategies mainly rely on immunosuppression with steroids and/or steroid-sparing drugs, in order to switch off acute inflammation and prevent disease evolution. Anti-TNF drugs represent a valuable option for chronic refractory diseases; no specific anti-fibrotic treatment is currently available. Expert commentary: Future therapeutic strategies will have to specifically target mediators and pathways involved in the chronic and fibrotic phase of sarcoidosis, focusing on genetic/genomic biomarkers and predictors of disease phenotype.

Keywords: Sarcoidosis; TNF-α; Th17; biologicals; fibrosis; granuloma; pathogenesis; therapy.