Molecular framework for response to imatinib mesylate in systemic sclerosis

Lorinda Chung, David F. Fiorentino, Maya J. BenBarak, Adam S. Adler, Melissa M. Mariano, Ricardo T. Paniagua, Ausra Milano, M. Kari Connolly, Boris D. Ratiner, Robert L. Wiskocil, Michael L. Whitfield, Howard Y. Chang, William H. Robinson

Research output: Contribution to journalArticlepeer-review

97 Scopus citations


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 PDGFRβ 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 PDGFRβ 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.

Original languageEnglish (US)
Pages (from-to)584-591
Number of pages8
JournalArthritis and rheumatism
Issue number2
StatePublished - Feb 2009

ASJC Scopus subject areas

  • Immunology and Allergy
  • Rheumatology
  • Immunology
  • Pharmacology (medical)


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