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Rheumatology Advance Access published online on October 25, 2009

Rheumatology, doi:10.1093/rheumatology/kep265
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© The Author 2009. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Fibrocyte activation in rheumatoid arthritis

Carole L. Galligan1, Katherine A. Siminovitch2, Edward C. Keystone3, Vivian Bykerk3, Omar D. Perez4 and Eleanor N. Fish1

1Toronto General Research Institute, University Health Network, 2Mount Sinai Hospital Samuel Lunenfeld, Toronto Hospital Research Institutes, 3Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada and 4Tocagen, San Diego, CA, USA.

Correspondence to: Eleanor N. Fish, Toronto General Research Institute, University Health Network, 67 College Street, 4-424, Toronto, Ontario M5G 2M1, Canada. E-mail: en.fish{at}utoronto.ca


   Abstract

Objectives. RA is a common, relapsing autoimmune disease primarily affecting the joints. Fibroblast-like synovial (FLS) cells are thought to be responsible for pannus formation and secretion of factors that recruit leucocytes to affected joints, thereby promoting bone and cartilage destruction. Fibrocytes are multipotent circulating stem cells that may have a role in RA pathogenesis, perhaps as the precursors of the FLS cells, or by regulating FLS cell function.

Methods. We utilized multidimensional phospho-specific flow cytometry to characterize the activation status of peripheral blood (PB) fibrocytes derived from human RA patients at different stages of disease and from mice with CIA.

Results. Human PB fibrocytes from RA patients exhibited phosporylation activation of the p44/42 and p38 MAP kinases (MAPKs), and STAT3 (signal transducer and activator of transcription) and STAT-5 early in disease, within the first year of diagnosis. Similarly, in murine CIA, an increase in the total number of PB phosphoSTAT5-positive fibrocytes was observed at early time points in disease. Notably, in the affected paws of mice with CIA, we identified an increased number of fibrocytes, in contrast to the paws of control mice.

Conclusions. These data suggest that activated fibrocytes may influence the disease process in RA and may serve as surrogate markers for disease in the PB of affected patients.

KEY WORDS: Rheumatoid arthritis, Peripheral blood, Stem cell, FACS, Collagen-induced arthritis

Submitted 17 December 2008; revised version accepted 27 July 2009.
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