Figure S1.

Pedigrees of the patients, lung pathology of F1.P1, and concentration of NF-κB–related cytokines observed in the patients. (A) Pedigrees of the four families (F) in this study. Circles (females) and squares (males) blackened and clear with vertical lines indicate respectively symptomatic and asymptomatic carriers of the annotated heterozygous mutation in COPA. Diagonal bars indicate deceased individuals. Arrows and asterisks indicate, respectively, index cases and asymptomatic individuals screened for the mutation. Numbers inside the symbols indicate the number of individuals of the same gender. (B) Histopathological analysis of the lung biopsy of F1.P1. (B.1–B.4) H&E and Giemsa staining showing subpleural emphysema with local interstitial thickening of the remaining interalveolar septa (B.1 and B.2), lymphoid follicles (arrows; B.3), and mildly cellular fibroblastic foci (star), as well as mild macrophagic alveolitis (arrow; B.4, B.5, B.6, and B.7). Immunohistochemical staining identified a majority of CD20⁺ B cells within the B cell follicles, scattered CD5⁺ T cells in the interstitium, and the presence of rare macrophages (CD68⁺ cells) within the alveoli. (B.8) Anti-smooth muscle actin (SMA) staining demonstrating normal staining of vessels and absence of myofibroblastic proliferation in the interstitium. Original magnification: ×4 (B.1; scale bar, 1 mm), ×10 (B.2, B.3, B.6, and B.7; scale bars, 400 µm), ×40 (B.4, B.5, and B.8; scale bars, 100 µm). (C) Concentrations of IL-6 protein (normal < 10 pg /ml), IL-10 protein (normal < 10 pg /ml), and TNF-α protein (normal < 20 pg/ml) measured in the plasma of COPA patients (n = 5 samples from five symptomatic patients and n = 2 samples from two asymptomatic carriers). The dotted lines indicate the normal values. Red lines depict median values.