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Rheumatology Advance Access published online on September 13, 2005
Rheumatology, doi:10.1093/rheumatology/kei088
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© The Author 2005. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org
Received March 15, 2005
Accepted August 1, 2005

Original Papers

Circulating levels of active transforming growth factor {beta}1 are reduced in diffuse cutaneous systemic sclerosis and correlate inversely with the modified Rodnan skin score

M. Dziadzio 1, R. E. Smith 1, D. J. Abraham 1, C. M. Black 1, and C. P. Denton 1*

1 Centre for Rheumatology and Connective Tissue Diseases, Royal Free and University College Medical School, University College, London, UK

* To whom correspondence should be addressed.
C. P. Denton, E-mail: c.denton{at}medsch.ucl.ac.uk


  Abstract

Objectives. To determine the relationship between clinical features and circulating levels of active transforming growth factor (TGF) {beta}1 in the major subsets of systemic sclerosis (SSc).

Methods. In a cross-sectional study cases of diffuse cutaneous SSc (dose) (n=27) or limited cutaneous SSc (dose) (n=20) were compared with healthy controls (n=22). Active and total TGF{beta}1 was measured in serum and plasma by a high-sensitivity enzyme-linked immunosorbent assay.

Results. There were no significant differences between levels of total serum TGF{beta}1. However, cases of dcSSc had lower levels of active TGF{beta}1 than cases of lcSSc or controls. In addition, more cases of dcSSc (18/27; 66%, P<0.025) had no detectable active TGF{beta}1 than controls (7/22, 32%) or lcSSc (7/20, 35%). In dcSSc, serum active TGF{beta}1 levels correlated negatively with skin score and positively with disease duration.

Conclusions. Contrary to expectation, levels of active TGF{beta}1 are reduced in dcSSc and this correlates with two variables known to associate with disease activity, shorter duration and more extensive skin sclerosis. This suggests that active TGF{beta}1 may be sequestered in active involved SSc skin and that serum levels are reduced despite strong evidence implicating TGF{beta} isoforms in the pathogenesis of fibrosis. Our findings may have implications for systemic TGF{beta}-trapping therapies in this disease.

Keywords: Scleroderma; Systemic sclerosis; Biological markers; Severity of illness index; Transforming growth factor beta.
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