Current Rheumatology Reports

, Volume 13, Issue 1, pp 28–36 | Cite as

A Unifying Hypothesis for Scleroderma: Identifying a Target Cell for Scleroderma

  • William M. MahoneyJr
  • Jo Nadine Fleming
  • Stephen M. SchwartzEmail author


We propose that a recent change in the conception of the role of type 1 interferon and the identification of adventitial stem cells suggests a unifying hypothesis for scleroderma. This hypothesis begins with vasospasm. Vasospasm is fully reversible unless, as proposed here, the resulting ischemia leads to apoptosis and activation of type 1 interferon. The interferon, we propose, initiates immune amplification, including characteristic scleroderma-specific antibodies. We propose that the interferon also acts on adventitial stem cells, producing myofibroblasts, rarefaction, and intimal hyperplasia—three morphologic changes that characterize this disease. Regulator of G-protein signaling 5 (RGS5), a regulator of vasoactive G-protein–coupled receptors, is a cell type–specific marker of pericytes and scleroderma myofibroblasts. RGS5 may provide a key link between initial hyperplasia and fibrosis in this disease.


Type 1 interferon Vasculopathy Fibrosis Adventitial stem cell RGS5 



Drs. Mahoney, Fleming, and Schwartz have received grant support from the Scleroderma Research Foundation.


No potential conflicts of interest relevant to this article were reported.


Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

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Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • William M. MahoneyJr
    • 1
  • Jo Nadine Fleming
    • 1
  • Stephen M. Schwartz
    • 1
    Email author
  1. 1.Department of Pathology, Center for Cardiovascular BiologyUniversity of Washington School of MedicineSeattleUSA

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