A modified model of graft-versus-host–induced systemic sclerosis (scleroderma) exhibits all major aspects of the human disease
Article first published online: 5 APR 2004
Copyright © 2004 by the American College of Rheumatology
Arthritis & Rheumatism
Volume 50, Issue 4, pages 1319–1331, April 2004
How to Cite
Ruzek, M. C., Jha, S., Ledbetter, S., Richards, S. M. and Garman, R. D. (2004), A modified model of graft-versus-host–induced systemic sclerosis (scleroderma) exhibits all major aspects of the human disease. Arthritis & Rheumatism, 50: 1319–1331. doi: 10.1002/art.20160
- Issue published online: 5 APR 2004
- Article first published online: 5 APR 2004
- Manuscript Accepted: 7 JAN 2004
- Manuscript Received: 4 JUN 2003
- Genzyme Corporation
Diffuse systemic sclerosis (SSc; scleroderma) is a debilitating disease characterized by excessive dermal fibrosis with later progression to internal organs. In addition to the fibrotic component, major aspects of the disease include vascular or circulatory involvement and immune dysregulation evidenced by inflammatory cells in affected tissues and production of autoantibodies. Many animal models resembling this disease have been studied, including genetic models in mice and chickens, challenge with chemicals such as bleomycin or vinyl chloride to induce fibrosis, and models of graft-versus-host (GVH)–induced disease using certain strains of mice with differences in minor histocompatibility loci. The present studies were undertaken to determine if alteration of the induction of GVH-induced scleroderma could result in a model that more fully represented the human condition.
Disease was induced by injection of spleen cells from B10.D2 mice into BALB/c mice deficient in mature T and B cells (recombination-activating gene 2 targeted). Dermal thickening, collagen deposition, vasoconstriction, and parameters of immunity were analyzed.
Similar to the human disease, this modified GVH model of SSc demonstrated evidence of dermal thickening, particularly in the extremities, progressive fibrosis of internal organs, vasoconstriction and altered expression of vascularity markers in skin and internal organs, early immune activation, inflammation in skin and internal organs, and autoantibody generation.
This modified model of GVH-induced SSc exhibits all major components of human disease and is likely to contribute to better understanding of the disease mechanisms and, ultimately, improved treatments for patients.