Table 1.

Knowledge gaps in the pathogenesis of sarcoidosis

Genetic knowledge gaps

Understanding of the relationships between genotype and clinical phenotype is limited.

Understanding of genetic factors influencing immunologic variability is limited.

The role played by epigenetic factors (noncoding RNA, methylation, histone acetylation) in sarcoidosis is limited.

Knowledge gaps relating to environmental factors

The role of microbial and nonmicrobial antigens in the pathogenesis of sarcoidosis has not been firmly established.

Environmental factors that modify sarcoidosis disease course remain unknown.

The role played by the microbiome (lung, gastrointestinal tract) remains to be determined.

Knowledge gaps of the immunology of sarcoidosis

The role of T-cell subsets remains controversial.

The role of macrophage polarization in sarcoidosis granuloma formation is unclear.

The role of B cells remains largely unexplored.

The complex interaction among these cell lines during granuloma formation is difficult to model, and, as such, is largely unknown.