Differential diagnosis of sarcoidosis and tuberculosis using Mycobacterium tuberculosis-specific blood immune signatures 3700

Description Sarcoidosis is a granulomatous systemic inflammatory disease predominantly affecting the lungs. It shares histopathological, clinical and immune features with tuberculosis (TB). There are currently no diagnostic tests to formally identify sarcoidosis; instead, there is a need to first rule out the presence of other diseases, including TB. Here, we characterized Mycobacterium tuberculosis (Mtb)-specific immune responses in the blood of pulmonary sarcoidosis patients in comparison to TB disease, Mtb-sensitized, and non-sensitized healthy controls using flow cytometry and transcriptomics. We found that sarcoidosis was associated with i) a marked reduction in the frequency of antigen-reactive T cells in response to both Mtb peptides and Mtb lysate, ii) increased frequency of monocytes ex vivo and after in vitro stimulation, and iii) increased expression of monocyte-associated phagocytic genes compared to Mtb-infected and healthy cohorts. A combination of Mtb-specific T cell and monocyte gene or flow cytometry signatures in Mtb-stimulated PBMC could efficiently distinguish sarcoidosis from TB disease with high specificity (90-100%) and sensitivity (89-100%) and, to a lower extent, from Mtb-sensitized and non-sensitized healthy controls (69-91% specificity, and 73-89% sensitivity). These biomarkers offer promising aspects for developing accurate diagnosis tests for the differential diagnosis of sarcoidosis and TB.