Severe Pulmonary Fibrosis as the First Manifestation of Interferonopathy (TMEM173 Mutation)

Chest. 2016 Sep;150(3):e65-71. doi: 10.1016/j.chest.2016.02.682.


We report three cases of pulmonary disease suggesting fibrosis in two familial and one sporadic case. Pulmonary symptoms were associated with various clinical features of systemic inflammation and vasculitis involving the skin, and appeared at different ages. A strong interferon signature was found in all three cases. Disease was not responsive to corticosteroids, and lung transplantation was considered for all three subjects at an early age. One of them underwent double-lung transplantation, but she immediately experienced a primary graft dysfunction and died soon after. Recognized causes of familial interstitial lung disease were all excluded. All three subjects had a mutation in the previously described autoinflammatory disease called SAVI (stimulator of interferon genes [STING]-associated vasculopathy with onset in infancy). These cases emphasize the need to consider this possibility in children and young adults with lung fibrosis after common causes have been ruled out.

Keywords: TMEM173; autoinflammatory disease; pulmonary fibrosis; vasculopathy.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Autoimmune Diseases / diagnostic imaging
  • Autoimmune Diseases / genetics*
  • Autoimmune Diseases / immunology
  • Autoimmune Diseases / pathology
  • Chilblains / immunology
  • Child
  • Fatal Outcome
  • Female
  • Humans
  • Infant
  • Inflammation / diagnostic imaging
  • Inflammation / genetics*
  • Inflammation / immunology
  • Inflammation / pathology
  • Male
  • Membrane Proteins / genetics*
  • Mutation*
  • Pulmonary Fibrosis / diagnostic imaging
  • Pulmonary Fibrosis / genetics*
  • Pulmonary Fibrosis / immunology
  • Pulmonary Fibrosis / pathology
  • Severity of Illness Index
  • Tomography, X-Ray Computed


  • Membrane Proteins
  • STING1 protein, human