Volume 150, Issue 3, Pages e65-e71 (September 2016) Severe Pulmonary Fibrosis as the First Manifestation of Interferonopathy (TMEM173 Mutation)  Cécile Picard, MD, Guillaume Thouvenin, MD, Caroline Kannengiesser, MD, PhD, Jean-Christophe Dubus, MD, PhD, Nadia Jeremiah, PhD, Frédéric Rieux-Laucat, PhD, Bruno Crestani, MD, PhD, Alexandre Belot, MD, PhD, Françoise Thivolet-Béjui, MD, PhD, Véronique Secq, MD, PhD, Christelle Ménard, Martine Reynaud-Gaubert, MD, PhD, Philippe Reix, MD, PhD  CHEST  Volume 150, Issue 3, Pages e65-e71 (September 2016) DOI: 10.1016/j.chest.2016.02.682 Copyright © 2016 American College of Chest Physicians Terms and Conditions

Figure 1 A, B, C, High resolution thoracic CT of the chest of familial (A and B) and sporadic (C) cases. Note the presence of cystic lesions (paraseptal emphysema) in upper lobes in the three cases. In case 1 (A), there is a clear subpleural distribution in the upper lobes, and a right-side predominance of the lesion in case 3 (C). Ground glass areas were mainly found in the lower lobes in case 1 (A) and case 3 (C). CHEST 2016 150, e65-e71DOI: (10.1016/j.chest.2016.02.682) Copyright © 2016 American College of Chest Physicians Terms and Conditions

Figure 2 A, B, Chilblain lesions involving the heel (A) and the ear (B) of case 1. CHEST 2016 150, e65-e71DOI: (10.1016/j.chest.2016.02.682) Copyright © 2016 American College of Chest Physicians Terms and Conditions

Figure 3 A, B, C, Lung tissue from case 1 depicts emphysematous lesions in subpleural location and in some alveolar spaces (A, Hematoxylin-eosin-safran [HES] staining; magnification ×25), lymphoid aggregates within the parenchyma with intra-alveolar cholesterol crystal clefts (B, HES staining; magnification ×40). Note that there were no vascular lesion (C, HES staining; magnification ×40). D, Lung tissue from case 2 shows severe fibrosis and lymphoid infiltrates (HES staining; magnification ×25). E, Lymphoid follicles in lung parenchyma (left) (case 1; magnification ×40). Immunohistochemistry with anti-CD20 (middle) and anti-CD3 (right) antibodies showed that lymphoid aggregates were predominantly composed of B-lymphocytes and of scattered T-lymphocytes. CHEST 2016 150, e65-e71DOI: (10.1016/j.chest.2016.02.682) Copyright © 2016 American College of Chest Physicians Terms and Conditions

Figure 4 A, B, Family pedigrees of the 3 cases with V155M mutation in TMEM173. C, D, Increased level of expression of interferon (IFN)-stimulated genes in peripheral blood (type I IFN signature) of case 1 (C) and 3 (D). F = father; H = heterozygous mutated gene; IFI = interferon induced protein; ISG = interferon stimulated gene; M = mother; NM = nonmutated gene; PBMC = peripheral blood mononuclear cell; PHA = phytohaemagglutinin; RQ = relative quantification; RSAD2 = radical S-adenosyl methionine domain-containing protein 2; SIGLEC1 = sialic-acid-binding immunoglobulin-like lectin 1. CHEST 2016 150, e65-e71DOI: (10.1016/j.chest.2016.02.682) Copyright © 2016 American College of Chest Physicians Terms and Conditions