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Abstract
Sarcoidosis and tuberculosis (TB) are two granulomatous diseases that often share overlapping clinical features, including uveitis. We measured 368 inflammation-related proteins in serum in both diseases, with and without uveitis from two distinct geographically separated cohorts: sarcoidosis from the Netherlands and TB from Indonesia. A total of 192 and 102 differentially expressed proteins were found in sarcoidosis and active pulmonary TB compared to their geographical healthy controls, respectively. While substantial overlap exists in the immune-related pathways involved in both diseases, activation of B cell activating factor (BAFF) signaling and proliferation-inducing ligand (APRIL) mediated signaling pathways was specifically associated with sarcoidosis. We identified a B-lymphocyte activation signature consisting of BAFF, TNFRSF13B/TACI, TRAF2, IKBKG, MAPK9, NFATC1, and DAPP1 that was associated with sarcoidosis, regardless of the presence of uveitis. In summary, a difference in B-lymphocyte activation is a key discriminative immunological feature between sarcoidosis/ocular sarcoidosis (OS) and TB/ocular TB (OTB).
Sarcoidosis patients exhibit higher level of serum B cell activation signature compared to tuberculosis, regardless of uveitis manifestation.
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1 Erasmus University Medical Center, Department of Ophthalmology, Rotterdam, the Netherlands (GRID:grid.5645.2) (ISNI:0000 0004 0459 992X); Erasmus University Medical Center, Department of Internal Medicine Section Allergy & Clinical Immunology, Rotterdam, the Netherlands (GRID:grid.5645.2) (ISNI:0000 0004 0459 992X); Erasmus University Medical Center, Laboratory Medical Immunology, Department of Immunology, Rotterdam, the Netherlands (GRID:grid.5645.2) (ISNI:0000 0004 0459 992X); Cipto Mangunkusumo Hospital, Department of Ophthalmology, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia (GRID:grid.9581.5) (ISNI:0000 0001 2019 1471)
2 Erasmus University Medical Center, Laboratory Medical Immunology, Department of Immunology, Rotterdam, the Netherlands (GRID:grid.5645.2) (ISNI:0000 0004 0459 992X)
3 Erasmus University Medical Center, Department of Internal Medicine Section Allergy & Clinical Immunology, Rotterdam, the Netherlands (GRID:grid.5645.2) (ISNI:0000 0004 0459 992X); Erasmus University Medical Center, Laboratory Medical Immunology, Department of Immunology, Rotterdam, the Netherlands (GRID:grid.5645.2) (ISNI:0000 0004 0459 992X); Erasmus University Medical Center, Academic Center for Rare Immunological Diseases (Rare Immunological Disease Center), Rotterdam, the Netherlands (GRID:grid.5645.2) (ISNI:0000 0004 0459 992X)
4 Erasmus University Medical Center, Department of Ophthalmology, Rotterdam, the Netherlands (GRID:grid.5645.2) (ISNI:0000 0004 0459 992X)
5 Erasmus University Medical Center, Laboratory Medical Immunology, Department of Immunology, Rotterdam, the Netherlands (GRID:grid.5645.2) (ISNI:0000 0004 0459 992X); Erasmus University Medical Center, Academic Center for Rare Immunological Diseases (Rare Immunological Disease Center), Rotterdam, the Netherlands (GRID:grid.5645.2) (ISNI:0000 0004 0459 992X)
6 Erasmus MC University Medical Center Rotterdam, Department of Bioinformatics, Rotterdam, the Netherlands (GRID:grid.5645.2) (ISNI:0000 0004 0459 992X)
7 Erasmus University Medical Center, Department of Internal Medicine Section Allergy & Clinical Immunology, Rotterdam, the Netherlands (GRID:grid.5645.2) (ISNI:0000 0004 0459 992X)
8 Tan Tock Seng Hospital, National Healthcare Group Eye Institute, Singapore, Singapore (GRID:grid.240988.f) (ISNI:0000 0001 0298 8161); Nanyang Technological University, Lee Kong Chian School of Medicine, Singapore, Singapore (GRID:grid.59025.3b) (ISNI:0000 0001 2224 0361); Duke NUS University, Ophthalmology and Visual Sciences Academic Clinical Program, Singapore, Singapore (GRID:grid.428397.3) (ISNI:0000 0004 0385 0924); Singapore Eye Research Institute, Singapore, Singapore (GRID:grid.272555.2) (ISNI:0000 0001 0706 4670); Moorfields Eye Hospital, London, United Kingdom (GRID:grid.439257.e) (ISNI:0000 0000 8726 5837)
9 Erasmus University Medical Center, Department of Internal Medicine Section Allergy & Clinical Immunology, Rotterdam, the Netherlands (GRID:grid.5645.2) (ISNI:0000 0004 0459 992X); Erasmus University Medical Center, Laboratory Medical Immunology, Department of Immunology, Rotterdam, the Netherlands (GRID:grid.5645.2) (ISNI:0000 0004 0459 992X)
10 Cipto Mangunkusumo Hospital, Department of Ophthalmology, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia (GRID:grid.9581.5) (ISNI:0000 0001 2019 1471)