Supplementary Material for: A Familial History of Pulmonary Fibrosis in Patients with Chronic Hypersensitivity Pneumonitis

<b><i>Background:</i></b> Hypersensitivity pneumonitis (HP) is an immunologically mediated lung disease induced by the inhalation of a variety of antigens. Patients with chronic HP often have a family history of pulmonary fibrosis. This strongly suggests that both genetic and environmental factors play an important role in the pathogenesis of chronic HP. <b><i>Objectives:</i></b> We aimed to investigate the epidemiology and clinical features of chronic HP patients with a family history of pulmonary fibrosis. <b><i>Methods:</i></b> We retrospectively reviewed the clinical information of 114 cases diagnosed with chronic HP with insidious onset between 1992 and 2009. <b><i>Results:</i></b> Twenty cases (17.5%) were identified as having a family history of pulmonary fibrosis. All of these patients had lived apart from their afflicted relatives for at least several decades. The familial cases were younger than the nonfamilial cases at onset (57.5 ± 9.6 vs. 64.0 ± 7.0 years old, p = 0.008). The predicted vital capacity percentage and partial pressure of oxygen in arterial blood gas were significantly higher in the familial cases. There were no differences between the 2 groups in gender, smoking history, bronchoalveolar lavage fluid profile, radiologic findings or other clinical features. <b><i>Conclusions:</i></b> We found a familial clustering in patients with chronic HP. Various factors including genetic susceptibility to pulmonary fibrosis and environmental factors may contribute to the development of familial chronic HP

Supplementary Material for: Up-Regulation of CD74 Expression in Parietal Epithelial Cells in a Mouse Model of Focal Segmental Glomerulosclerosis

<i>Background/Aims:</i> De novo expression of CD44 is considered as a marker of parietal epithelial cell (PEC) activation. The aim of our study was to explore CD74 expression, which can form a complex with CD44, in PECs during the progression of focal segmental glomerulosclerosis (FSGS). To clarify the role of CD74 expression and of its interaction with CD44, we generated a new mouse model with enhanced PEC activation through lipopolysaccharide (LPS) application to adriamycin (ADR)-induced nephropathy mice (LPS-treated ADR mice). <i>Methods:</i> As a new model, LPS was intraperitoneally injected into the mice 3 weeks after ADR injection. The mice were divided into 3 categories: control mice, ADR mice and LPS-treated ADR mice. Renal function parameters, histologic changes and immunohistochemical expression of CD74 and other PEC activation markers were analyzed after LPS application. <i>Results:</i>After LPS stimulation, the glomeruli were characterized by enlarged epithelial cells with strong CD74 expression, followed by pseudo-crescent formation. By double staining, CD74-positive enlarged cells showed co-expression of classical PEC markers, but not of <i>Lotus tetragonolobus</i> lectin (marker of proximal tubular cells), suggesting amplification of PEC activation. Time-course analysis displayed marked upregulation of CD74 expression during rapid PEC activation compared with CD44. Additionally, the time-dependent change in ERK phosphorylation showed a similar pattern to CD74. <i>Conclusion:</i> Our results indicate that CD74 can be a marker for PEC activation in FSGS. By modifying the ADR mouse model through LPS treatment, we found that CD74 upregulation better reflects a rapid amplification of PEC activation than CD44 expression