A serum B-lymphocyte activation signature is a key distinguishing feature of the immune response in sarcoidosis compared to tuberculosis

• DOI: 10.1038/s42003-024-06822-1
• Publication Date: 2024-09-10T18:02:32Z
• Authors: Ikhwanuliman Putera; Benjamin Schrijver; P. Martijn Kolijn; Astrid C. van Stigt; Josianne C. E. M....; Hanna IJspeert; Nicole M. A. Nagt...; Sigrid M. A. Swag...; Jan A. M. van Laar; Rupesh Agrawal; Saskia M. Rombach; P. Martin van Hagen; Rina La Distia Nora; Willem A. Dik
• Keywords: Signature (topology); Feature (linguistics)

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).