NHLRC2 and immune cell expression in FINCA disease: a severe interstitial lung disease of infancy

Abstract FINCA disease (fibrosis, neurodegeneration, and cerebral angiomatosis) is a recently identified multiorgan disease with pathogenic variants in the NHL repeat containing 2 ( NHLRC2 ) gene. The patients with FINCA disease suffer from recurrent respiratory infections, respiratory failure, and interstitial lung disease. The aim of this study was to evaluate the expression of NHLRC2 and immune cells in the lungs of patients with FINCA disease. Surgical lung biopsies and lung tissue samples from autopsies of three FINCA patients, an age-matched control, and adult controls were analyzed by immunohistochemical staining against NHLRC2 antibody. mRNA expression of NHLRC2 was studied by mRNA in situ hybridization. Lung tissue samples were stained also for CD3, CD4, CD8, CD20, and CD68 that are markers of various immune cells. In FINCA disease, NHLRC2 was mainly expressed in hyperplastic alveolar epithelial cells, bronchial epithelial cells, and alveolar macrophages. In controls, the highest expression was seen in type II alveolar epithelial cells, bronchial epithelial cells, and macrophages. Numbers of CD8 + and CD68 + immune cells were higher in lung biopsies of FINCA patients than those in a control. Based on our findings, FINCA patients expressed NHLRC2 protein and mRNA in their lungs. Furthermore, an increased expression of macrophages and T-cells including both T-helper and cytotoxic T-cells were observed suggesting an association of the immune mechanisms in the pathogenesis of interstitial lung disorder in FINCA disease.