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

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 patie...

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Bibliographic Details
Published in:Journal of leukocyte biology 2009-01, Vol.85 (1), p.81-87
Main Authors: Comite, Gabriele, Rossi, Carlo M., Marinosci, Alessandro, Lolmede, Karine, Baldissera, Elena, Aiello, Patrizia, Mueller, Ruediger B., Herrmann, Martin, Voll, Reinhard E., Rovere‐Querini, Patrizia, Sabbadini, Maria Grazia, Corti, Angelo, Manfredi, Angelo A.
Format: Article
Language:English
Subjects:
arthritis
Arthritis, Rheumatoid - blood
Arthritis, Rheumatoid - pathology
Arthritis, Rheumatoid - physiopathology
Autoantibodies - blood
Biomarkers - blood
cell activation
Cells, Cultured
Chemokine CCL2 - metabolism
Chromogranin A - blood
Chromogranin A - pharmacology
Endothelial Cells - cytology
Endothelial Cells - drug effects
Endothelium, Vascular - cytology
Feedback, Physiological
Female
HMGB1
Humans
inflammation
Inflammation Mediators - physiology
Intercellular Adhesion Molecule-1 - metabolism
Male
Microvessels - cytology
Middle Aged
neuropeptides
Peripheral Nervous System Diseases - physiopathology
Prospective Studies
Pulmonary Fibrosis - physiopathology
Serositis - physiopathology
Synovial Membrane - pathology
Tumor Necrosis Factor-alpha - pharmacology
Tumor Necrosis Factor-alpha - physiology
Vasculitis - physiopathology
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Summary: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.
ISSN:0741-5400
1938-3673
DOI:10.1189/jlb.0608358