Mechanisms of scleroderma-induced lung disease

Proc Am Thorac Soc. 2007 Aug 15;4(5):434-8. doi: 10.1513/pats.200608-152MS.


Scleroderma (systemic sclerosis) is characterized by dermal thickening and is subclassified, on the basis of the pattern of skin involvement, as diffuse or limited cutaneous disease. The lung fibrosis associated with systemic sclerosis is histopathologically nonspecific interstitial pneumonia and occurs to various extents. A key determinant of the development of lung fibrosis is the carriage of the anti-DNA topoisomerase II autoantibody, which is driven by genotype, particularly major histocompatibility complex class II alleles. Epithelial and endothelial cell injury initiates lung pathology and the local milieu expresses all the expected components of an immune/inflammatory chronic process that has fibrosis as an associated feature. However, novel concepts of the pathogenesis include the role of epithelial mesenchymal transition as a source of myofibroblasts following epithelial cell triggering and the concept of fibroblast heterogeneity in terms of both origin and function. Focus on the poles of the pathogenetic process, than on the redundancy of multiple mediator pathways, may provide more translational ideas in terms of elucidating how epithelial triggering initiates the downstream events and how fibroblast proliferation and connective matrix deposition is controlled, together with establishing how the process of autoantibody formation relates to the pathophysiologic events. Although much remains to be learned about the mechanisms of scleroderma-induced lung disease the clarity of the questions is improving.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Connective Tissue Growth Factor
  • Epithelial Cells / physiology
  • Genetic Predisposition to Disease
  • Humans
  • Hypertension, Pulmonary / etiology
  • Hypertension, Pulmonary / physiopathology
  • Immediate-Early Proteins / physiology
  • Indians, North American / genetics
  • Intercellular Signaling Peptides and Proteins / physiology
  • Major Histocompatibility Complex / genetics
  • Oklahoma
  • Osteonectin / genetics
  • Osteonectin / physiology
  • Pulmonary Fibrosis / etiology*
  • Pulmonary Fibrosis / genetics
  • Pulmonary Fibrosis / pathology
  • Pulmonary Fibrosis / physiopathology*
  • Scleroderma, Systemic / complications*
  • Scleroderma, Systemic / pathology
  • Scleroderma, Systemic / physiopathology*


  • CCN2 protein, human
  • Immediate-Early Proteins
  • Intercellular Signaling Peptides and Proteins
  • Osteonectin
  • Connective Tissue Growth Factor