Communications Biology (Sep 2024)

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

  • Ikhwanuliman Putera,
  • Benjamin Schrijver,
  • P. Martijn Kolijn,
  • Astrid C. van Stigt,
  • Josianne C. E. M. ten Berge,
  • Hanna IJspeert,
  • Nicole M. A. Nagtzaam,
  • Sigrid M. A. Swagemakers,
  • Jan A. M. van Laar,
  • Rupesh Agrawal,
  • Saskia M. Rombach,
  • P. Martin van Hagen,
  • Rina La Distia Nora,
  • Willem A. Dik

DOI
https://doi.org/10.1038/s42003-024-06822-1
Journal volume & issue
Vol. 7, no. 1
pp. 1 – 13

Abstract

Read online

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).