Immunity & infection
Tuberculosis (TB) is the leading cause of death by infectious diseases worldwide. Sarcoidosis is a lung inflammatory disease with unknown etiology that is often misdiagnosed as TB. It also forms granulomas, and shares the same type I interferon whole blood transcriptomic signature widely described in TB. Interestingly, TB-specific CD4 T cell immune responses have been reported in sarcoidosis patients, and linked to pathology. We elected to compare transcriptomic signatures of circulating CD4 T cells in patients with sarcoidosis vs individuals with active or latent TB. TB antigen-specific CD4 T cell responses were interrogated using a pool of 300 TB-specific peptides known to elicit significant reactivity in TB infected individuals. Surprisingly, reactivity to the peptide pool was lower in the sarcoidosis cohort compared to the healthy, TB uninfected cohort. Conversely, sarcoidosis patients were associated with higher reactivity to polyclonal stimulation compared to both TB infected and uninfected cohorts. Both lack of TB-specific reactivity and higher polyclonal reactivity in sarcoidosis were associated with the expression of type I IFN genes, suggesting a dysregulation of this pathway in CD4 T cells in the context of sarcoidosis. We also found that the CD4 T cell compartment in sarcoidosis patients was enriched for effector T cells, which correlated with the expression of genes clusters associated with specific biological functions and cell types such as cytotoxicity and Tregs. Finally, we also identified some promising gene candidates that could be used for differential diagnostic between sarcoidosis and TB, and thus translated into new diagnostic tools.