Chest
Volume 150, Issue 3, September 2016, Pages e65-e71
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Selected Reports
Severe Pulmonary Fibrosis as the First Manifestation of Interferonopathy (TMEM173 Mutation)

https://doi.org/10.1016/j.chest.2016.02.682Get rights and content

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.

Section snippets

Cases 1 and 2

A 12-year-old boy (case 1) was referred for evaluation of lung transplantation at 11 years, 1 year after his mother died of an undifferentiated interstitial lung disease (ILD) (case 2). He was the first child of unrelated parents of Algerian origin. There was no history of neonatal respiratory distress. He was first investigated at the age of 5 years for chronic cough with digital clubbing. He was noted to have failure to thrive since the age of 1 year. At 11 years, high-resolution CT (HRCT)

Discussion

We report three additional cases of the recently described autoinflammatory syndrome linked to a gain-of-function mutation of TMEM173.1 This gene encodes the STING adaptor protein, and mutations are responsible for type-I IFN overproduction through an intracellular JAK-kinase pathway.4 Mutations involved a coding region (exon 5) of TMEM173, and three genetic variants have been described so far, the most common being c.463G>A (p.Val155Met).1, 5 De novo and inherited mutations have been related,1

Acknowledgments

Financial/nonfinancial disclosures: None declared.

Role of sponsors: The sponsor had no role in the design of the study, the collection and analysis of the data, or the preparation of the manuscript.

Other contributions: The authors thank Aurore Coulomb, MD, and Hubert Ducou Le Pointe, MD, PhD, for their expertise in pathology and radiology.

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Drs Picard and Thouvenin contributed equally to this manuscript.

FUNDING/SUPPORT: This work (exome sequencing) was supported by a grant “FPI-SPC” from Université Sorbonne ParisCité (B. C.) and the Chancellerie des Universités de Paris (legs Poix; C. K.).

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