Potential therapeutic targets to prevent organ damage in chronic pulmonary sarcoidosis

Sarcoidosis is a granulomatous inflammatory disease with high chances of reduced quality of life, irreversible organ damage, and reduced life expectancy when vital organs are involved. Any organ system can be affected, and the lungs are most often affected. There is no preventive strategy as the exact etiology is unknown, and complex immunogenetic and environmental factors determine disease susceptibility and phenotype. Present-day treatment options originated from clinical practice and are effective in many patients. However, a substantial percentage of patients suffer from unacceptable side effects or still develop refractory, threatening pulmonary or extrapulmonary disease.

As non-caseating granulomas, the pathological hallmark of disease, are assigned to divergent activation and regulation of the immune system, targets in relation to the possible triggers of granuloma formation and their sequelae were reviewed.

The immunopathogenesis underlying sarcoidosis has been a dynamic field of study. Several recent new insights give way to promising new therapeutic targets, such as certain antigenic triggers (e.g. from Aspergillus nidulans), mTOR, JAK-STAT and PPARγ pathways, the NRP2 receptor and MMP-12, which await further exploration. Clinical and trigger related phenotyping, and molecular endotyping will likely hold the key for precision medicine in the future.