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 journalArticle

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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 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
Volume60
Issue number2
DOIs
StatePublished - Feb 2009

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Systemic Scleroderma
Skin
Platelet-Derived Growth Factor Receptors
Diffuse Scleroderma
Gene Expression Profiling
Sclerosis
Protein-Tyrosine Kinases
Autoimmune Diseases
Fibrosis
Imatinib Mesylate
Biopsy
Gene Expression
Therapeutics

ASJC Scopus subject areas

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

Cite this

Chung, L., Fiorentino, D. F., BenBarak, M. J., Adler, A. S., Mariano, M. M., Paniagua, R. T., ... Robinson, W. H. (2009). Molecular framework for response to imatinib mesylate in systemic sclerosis. Arthritis and Rheumatism, 60(2), 584-591. https://doi.org/10.1002/art.24221

Molecular framework for response to imatinib mesylate in systemic sclerosis. / Chung, Lorinda; Fiorentino, David F.; BenBarak, Maya J.; Adler, Adam S.; Mariano, Melissa M.; Paniagua, Ricardo T.; Milano, Ausra; Connolly, M. Kari; Ratiner, Boris D.; Wiskocil, Robert L.; Whitfield, Michael L.; Chang, Howard Y.; Robinson, William H.

In: Arthritis and Rheumatism, Vol. 60, No. 2, 02.2009, p. 584-591.

Research output: Contribution to journalArticle

Chung, L, Fiorentino, DF, BenBarak, MJ, Adler, AS, Mariano, MM, Paniagua, RT, Milano, A, Connolly, MK, Ratiner, BD, Wiskocil, RL, Whitfield, ML, Chang, HY & Robinson, WH 2009, 'Molecular framework for response to imatinib mesylate in systemic sclerosis', Arthritis and Rheumatism, vol. 60, no. 2, pp. 584-591. https://doi.org/10.1002/art.24221
Chung L, Fiorentino DF, BenBarak MJ, Adler AS, Mariano MM, Paniagua RT et al. Molecular framework for response to imatinib mesylate in systemic sclerosis. Arthritis and Rheumatism. 2009 Feb;60(2):584-591. https://doi.org/10.1002/art.24221
Chung, Lorinda ; Fiorentino, David F. ; BenBarak, Maya J. ; Adler, Adam S. ; Mariano, Melissa M. ; Paniagua, Ricardo T. ; Milano, Ausra ; Connolly, M. Kari ; Ratiner, Boris D. ; Wiskocil, Robert L. ; Whitfield, Michael L. ; Chang, Howard Y. ; Robinson, William H. / Molecular framework for response to imatinib mesylate in systemic sclerosis. In: Arthritis and Rheumatism. 2009 ; Vol. 60, No. 2. pp. 584-591.
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