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Published on: September 14, 2021
Circulating levels of active transforming growth factor beta1 are reduced in diffuse cutaneous systemic sclerosis and
M Dziadzio1, R E Smith, D J Abraham
1Centre for Rheumatology, Royal Free and University College Medical School, University College London, London NW3 2PF, UK.
Objectives:
To determine the relationship between clinical features and circulating levels of active transforming growth factor (TGF) beta1 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 TGFbeta1 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 TGFbeta1. However, cases of dcSSc had lower levels of active TGFbeta1 than cases of lcSSc or controls. In addition, more cases of dcSSc (18/27; 66%, P < 0.025) had no detectable active TGFbeta1 than controls (7/22, 32%) or lcSSc (7/20, 35%). In dcSSc, serum active TGFbeta1 levels correlated negatively with skin score and positively with disease duration.
Conclusions:
Contrary to expectation, levels of active TGFbeta1 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 TGFbeta1 may be sequestered in active involved SSc skin and that serum levels are reduced despite strong evidence implicating TGFbeta isoforms in the pathogenesis of fibrosis. Our findings may have implications for systemic TGFbeta-trapping therapies in this disease.
