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

Cécile Picard (1, 2) , Guillaume Thouvenin (1, 3, 4) , Caroline Kannengiesser (5) , Jean-Christophe Dubus (6) , Nadia Jeremiah (7) , Frédéric Rieux-Laucat (7) , Bruno Crestani (8) , Alexandre Belot (9, 2) , Françoise Thivolet-Béjui (1) , Veronique Secq (6) , Christelle Ménard (3) , Martine Reynaud-Gaubert (10) , Philippe Reix (1, 11)

1 HFME - Hôpital Femme Mère Enfant [CHU - HCL]
2 Réponse immunitaire innée dans les maladies infectieuses et auto-immunes – Innate immunity in infectious and autoimmune diseases
3 CHU Trousseau [APHP]
4 CRSA - Centre de Recherche Saint-Antoine
5 Hopital Bichat, Departement de Genetique
6 TIMONE - Hôpital de la Timone [CHU - APHM]
7 IMAGINE - U1163 - Imagine - Institut des maladies génétiques
8 PHERE (UMR_S_1152 / U1152) - Physiopathologie et Epidémiologie des Maladies Respiratoires
9 Service de néphrologie, rhumatologie et dermatologie pédiatriques
10 Hôpital Nord [CHU - APHM]
11 LBBE - Laboratoire de Biométrie et Biologie Evolutive - UMR 5558

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.

Domaines: Maladies infectieuses

Cécile Picard, Guillaume Thouvenin, Caroline Kannengiesser, Jean-Christophe Dubus, Nadia Jeremiah, et al.. Severe Pulmonary Fibrosis as the First Manifestation of Interferonopathy (TMEM173 Mutation). Chest, 2016, 150 (3), pp.E65-E71. ⟨10.1016/j.chest.2016.02.682⟩. ⟨hal-01455776⟩