EPSTEIN-BARR-VIRUS REPLICATION WITHIN PULMONARY EPITHELIAL-CELLS IN CRYPTOGENIC FIBROSING ALVEOLITIS

Background - Cryptogenic fibrosing alveolitis (synonymous with idiopat hic pulmonary fibrosis) is a clinically heterogeneous condition in whi ch the precipitating factor is unclear. Both environmental and infecti ve factors have been implicated. An association between Epstein-Barr v irus (EBV) and cryptogenic fibrosing alveolitis was suggested over a d ecade ago by a study based on EBV serology, but the significance of th is has been unclear. Methods - Lung tissue obtained surgically from pa tients (n = 20) with cryptogenic fibrosing alveolitis was investigated for evidence of EBV replication and compared with lung tissue from 21 control patients. Fourteen of the 20 patients had received no specifi c therapy for cryptogenic fibrosing alveolitis at the time of biopsy. Monoclonal antibodies directed against the EBV viral antigens, EBV vir al capsid antigen (VCA) and gp 340/220 antigen, which are expressed du ring the lytic phase of the EBV life cycle, were studied. Results - Fo urteen (70%) ofthe 20 patients with cryptogenic fibrosing alveolitis w ere positive for both EBV VCA and gp 340/220 compared with two (9%) of the 21 controls. In the patients with cryptogenic fibrosing alveoliti s viral replication was localised to pulmonary epithelial cells using epithelial cell markers, and immunohistochemical analysis confirmed th e staining to be within type II alveolar cells. Conclusions - This is the first report of in vivo EBV replication within epithelial cells of the lower respiratory tract in an immunocompetent human host. Further more, this suggests that EBV may be an immune trigger or contribute to lung injury in cryptogenic fibrosing alveolitis, thus offering a pote ntial new avenue of treatment.