Differential diagnosis of sarcoidosis and tuberculosis using Mycobacterium tuberculosis-specific blood immune signatures 3700
Abstract 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. Topic Categories Translational and Interventional Immunology (TI)
Authors
- Coline HM van Moorsel (ORCID: https://orcid.org/0000-0002-2957-1670)
- Simone A. Joosten (ORCID: https://orcid.org/0000-0002-9878-0863)
- Monalisa Mondal
- Marcel Veltkamp (ORCID: https://orcid.org/0000-0001-7973-1604)
- Bjoern Peters (ORCID: https://orcid.org/0000-0002-8457-6693)
- Aruna Dharshan De Silva (ORCID: https://orcid.org/0000-0001-5291-9543)
- Alessandra Aiello (ORCID: https://orcid.org/0000-0003-2681-9383)
- Julie G. Burel (ORCID: https://orcid.org/0000-0003-1692-2758)
- Wonder P. Drake (ORCID: https://orcid.org/0000-0001-9406-3130)
- Leila Y. Chihab
- Pandurangan Vijayanand
- Thomas J. Scriba (ORCID: https://orcid.org/0000-0002-0641-1359)
- Grégory Seumois (ORCID: https://orcid.org/0000-0002-8164-6852)
- Delia Goletti (ORCID: https://orcid.org/0000-0001-8360-4376)
- Cecilia S. Lindestam Arlehamn (ORCID: https://orcid.org/0000-0001-7302-8002)
- Nabeela Khan (ORCID: https://orcid.org/0000-0003-3090-3772)
- Linda Petrone (ORCID: https://orcid.org/0000-0002-2593-3478)
- Fabrizio Palmieri (ORCID: https://orcid.org/0000-0001-8184-6291)
- Hannah Hillman (ORCID: https://orcid.org/0009-0002-5448-3143)
- Alice Wang (ORCID: https://orcid.org/0000-0002-1371-258X)
- Catherine Cheng (ORCID: https://orcid.org/0009-0007-5949-2205)
- Montse Janssen Bonás
- Krista E. van Meijgaarden
Institutions
- Statens Serum Institut (DK)
- University of Maryland, Baltimore (US)
- La Jolla Institute for Immunology (US)
- General Sir John Kotelawala Defence University (LK)
- Leiden University Medical Center (NL)
- University of California San Diego (US)
- Istituto Nazionale per le Malattie Infettive Lazzaro Spallanzani (IT)
- St. Antonius Ziekenhuis (NL)
- South African Tuberculosis Vaccine Initiative (ZA)
Publication Details
- Journal
- The Journal of Immunology
- Published
- 2025-11-01
- DOI
- https://doi.org/10.1093/jimmun/vkaf283.1470
- Primary Topic
- Sarcoidosis and Beryllium Toxicity Research
- Type
- article
- Field-Weighted Citation Impact
- 0.00