Idiopathic pulmonary fibrosis is associated with circulating antiepithelial antibodies.

PURPOSE: Idiopathic pulmonary fibrosis (IPF) is a restrictive fibrotic lung disease of uncertain etiology. Alveolar epithelial injury may be one of the inciting triggers in the pathogenesis of this disorder. We hypothesized that circulating antibodies to alveolar epithelial and endothelial cells may be involved in the pathogenesis of IPF.

METHODS: Antibodies to alveolar epithelial and endothelial cells were analyzed by indirect immunofluorescence using alveolar epithelial cells (A549) and human umbilical vein endothelial cells respectively. IgG and IgM antibodies in patients' serum were evaluated. Patterns of immunofluorescence, including membranous, cytoplasmic, and nuclear staining, were analyzed by fluorescence microscopy. The severity of immunofluorescence was divided into mild, moderate, and severe categories. Fifty-six patients (IPF = 28, non-IPF ILD = 9, non-ILD control = 19) were evaluated for antiepithelial antibodies, and 28 patients (IPF = 12, non-IPF ILD = 3, non-ILD control = 13) were studied for antiendothelial antibodies.

RESULTS: Compared with control subjects, serum from IPF patients displayed significantly higher IgG binding to alveolar epithelial cells (P = 0.041) with a membranous pattern of immunofluorescence. However, there was no significant difference in immunofluorescence with IgG on endothelial cells (P = 0.165). In terms of IgM antibodies, there was no differential fluorescence observed for either epithelial or endothelial cells.

CONCLUSIONS: There is evidence of increased IgG antibodies directed against alveolar epithelium in IPF. These antibodies may play a significant role in the pathogenesis of this fibrotic disorder. The findings of this study suggest further evaluation of the role of immune mediated alveolar epithelial injury in IPF.