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Arthritis Rheum. 2009 Feb;60(2):584-91. doi: 10.1002/art.24221.

Molecular framework for response to imatinib mesylate in systemic sclerosis.

Author information

1
Stanford University, Stanford, California, and VA Palo Alto Health Care System, Palo Alto, California.

Abstract

Systemic sclerosis (SSc) is an autoimmune disease in which the tyrosine kinases platelet-derived growth factor receptor (PDGFR) and Abl are hypothesized to contribute to the fibrosis and vasculopathy of the skin and internal organs. Herein we describe 2 patients with early diffuse cutaneous SSc (dcSSc) who experienced reductions in cutaneous sclerosis in response to therapy with the tyrosine kinase inhibitor imatinib mesylate. Immunohistochemical analyses of skin biopsy specimens demonstrated reductions of phosphorylated PDGFRbeta and Abl with imatinib therapy. By gene expression profiling, an imatinib-responsive signature specific to dcSSc was identified (P < 10(-8)). The response of these patients and the findings of the analyses suggest that PDGFRbeta and Abl play critical, synergistic roles in the pathogenesis of SSc, and that imatinib targets a gene expression program that is frequently dysregulated in dcSSc.

PMID:
19180499
PMCID:
PMC2638060
DOI:
10.1002/art.24221
[Indexed for MEDLINE]
Free PMC Article

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