Fig. 24.5  High-Resolution Computed Tomography of (a) non-UIP pattern (indeterminate) with ground-glass opacities and reticulation associated with (a) SFTPA1 mutation, (b) compound heterozygous

ABCA3 mutation and with (c) end-stage lung brosis associated with SFTPC mutation (note the artifact due orthopedic hardware in the spine)

Other Genetic Diseases That Can Cause

Fibrosing ILD

Heritable Forms of Pulmonary Fibrosis with Autoimmune Features

TMEM173

Ten initial pediatric and young adult patients with systemic infammation, peripheral vascular infammation with skin involvement and ILD, were associated with gain-of-function TMEM173 gene mutations [88, 89]. The TMEM173 gene encodes the stimulator of interferon gene (STING). The mutations are associated with a strong interferon signature in blood monocytes with increased interferon-induced cytokine levels in the serum that could be used as a screening test before genetic analysis. Screening for autoantibodies shows variable lupus-like positivity (antinuclear or antiphospholipid antibodies) and ANCA positivity has also been reported [88, 89]. Pulmonary brosis may lead to respiratory insuf -

ciency, lung transplantation, or death [89]. Janus kinase inhibitors (tofacitinib or ruxolitinib) have shown promising results for systemic infammation but appear to have less of an effect on ILD [90, 91].

COPA

Twenty-one patients from ve families were initially reported with arthritis, renal disease, and ILD that were associated with heterozygous COPA mutations, impairing endoplasmic–Golgi transport [92]. Similarly to patients carriers of TMEM173 gene mutations, COPA mutations induce a strong upregulation of interferon-stimulated genes [93]. Most of the patients (76%) were under 5 years of age, 95% had joint pain, and all had ILD or alveolar hemorrhage [92]. Screening for autoantibodies showed positivity for ANCA (71%), antinuclear antibodies (67%), and rheumatoid factor (43%). The nature of ANCA, such as anti-MPO or anti-PR3 positivity, is most often not speci ed.