Circulating chromogranin a reveals extra-articular involvement in patients with rheumatoid arthritis and curbs TNF-α-elicited endothelial activation

Gabriele Di Comite, Carlo M. Rossi, Alessandro Marinosci, Karine Lolmede, Elena Baldissera, Patrizia Aiello, Reinhard E. Voll, Patrizia Rovere-Querini, Maria Grazia Sabbadini, Angelo Corti, Angelo A. Manfredi, Ruediger B. Mueller, Martin Herrmann

Research output: Contribution to journalArticlepeer-review

Abstract

TNF-α plays an important role in the natural history of rheumatoid arthritis (RA), a systemic disease characterized by endothelial activation and synovial involvement with bone erosions. Neuroendocrine signals contribute as well to RA, but their role is poorly understood. We measured in 104 RA patients and in an equal number of sex-and age-matched, healthy controls the blood levels of chromogranin A (CgA), a candidate marker linking the neuroendocrine system to TNF-α-mediated vascular inflammation. CgA levels were significantly higher in patients with RA and remained stable over time. High levels of CgA were significantly associated with severe extra-articular manifestations, namely pulmonary fibrosis, rheumatoid vasculitis, serositis, and peripheral neuropathy. RA sera curbed the response of human microvascular endothelial cells to TNF-α, as assessed by the expression of ICAM-1, the release of MCP-1/CCL2, and the export of nuclear high-mobility group box 1; the effect abated in the presence of anti-CgA antibodies. The efficacy of the blockade was significantly correlated with the CgA concentration in the serum. The recombinant aminoterminal portion of CgA, corresponding to residues 1-78, had similar inhibitory effects on endothelial cells challenged with TNF-α. Our results suggest that enhanced levels of CgA identify patients with extra-articular involvement and reveal a negative feedback loop that limits the activation of endothelial cells in RA.

Original languageEnglish
Pages (from-to)81-87
Number of pages7
JournalJournal of Leukocyte Biology
Volume85
Issue number1
DOIs
Publication statusPublished - Jan 1 2009

Keywords

  • Arthritis
  • Cell activation
  • HMGB1
  • Inflammation
  • Neuropeptides

ASJC Scopus subject areas

  • Cell Biology
  • Immunology

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