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Disease Classification Using Molecular Signatures

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Scleroderma

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Abstract

Clinical presentation in patients with systemic sclerosis (SSc) is heterogeneous in terms of organ involvement and disease progression. Difficulty measuring this clinical heterogeneity has hindered the understanding of pathogenesis and development of effective treatments. Genome-wide profiling of SSc skin has measured this heterogeneity and shown that multiple, distinct gene expression subsets can be identified in SSc patients. Microarray analysis of skin provides more robust signatures than found in biopsy-derived fibroblasts and these signatures are remarkably consistent between lesional and non-lesional skin samples, indicative of the systemic nature of the disease. In addition to accurately permitting a molecular stratification of the well-described clinical subsets of limited and diffuse cutaneous SSc, gene expression studies of patients with diffuse scleroderma (dSSc) show reproducible, disease-specific gene expression indicating subsets of patients based on different patterns of gene expression. Notably, disease-specific gene expression points to specific pathways in SSc pathogenesis. Activation of these pathways appears to be associated with disease subsets, implicating different pathophysiological processes underlying skin pathology in different patient subsets. Targeted analysis of the level of expression of IFN- and TGF-β-responsive genes in the skin correlates strongly with the modified Rodnan skin score (mRSS) providing another tool for clinical management. Gene expression in peripheral blood and lung from SSc patients give further insights into the systemic response driving SSc pathogenesis.

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Author information

Authors and Affiliations

  1. Department of Genetics, Dartmouth Medical School, Hanover, NH, USA

    Michael L. Whitfield PhD

  2. Department of Medicine, Rheumatology Section, Boston University School of Medicine, Boston, MA, USA

    Robert Lafyatis MD

Authors
  1. Michael L. Whitfield PhD
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  2. Robert Lafyatis MD
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Correspondence to Michael L. Whitfield PhD .

Editor information

Editors and Affiliations

  1. Feinberg School of Medicine, Northwestern University, E. Huron Street 240, Chicago, 60611-2909, Illinois, USA

    John Varga

  2. Royal Free and University College, Medical School, University College London, Rowland Street, London, NW3 2PF, United Kingdom

    Christopher P. Denton

  3. School of Medicine, Div. Rheumatology, Johns Hopkins University, Eastern Avenue 5200, Baltimore, 21224, Maryland, USA

    Fredrick M. Wigley

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Whitfield, M.L., Lafyatis, R. (2012). Disease Classification Using Molecular Signatures. In: Varga, J., Denton, C., Wigley, F. (eds) Scleroderma. Springer, Boston, MA. https://doi.org/10.1007/978-1-4419-5774-0_8

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  • DOI: https://doi.org/10.1007/978-1-4419-5774-0_8

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  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4419-5773-3

  • Online ISBN: 978-1-4419-5774-0

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