DETECTION OF ANTI-CYTOKERATIN-8 ANTIBODY IN THE SERUM OF PATIENTS WITH CRYPTOGENIC FIBROSING ALVEOLITIS AND PULMONARY FIBROSIS ASSOCIATED WITH COLLAGEN VASCULAR DISORDERS

Background-It has been suggested that the humoral immune system plays a role in the pathogenesis of cryptogenic fibrosing alveolitis (CFA). Although circulating autoantibodies to lung protein(s) have been sugge sted, none of the lung proteins have been characterised. The purpose o f this study was to determine the antigen to which the serum from pati ents with pulmonary fibrosis reacted. Methods-The anti-A549 cell antib ody was characterised in a patient with CFA using Western immunoblotti ng and immunohistochemical staining of A549 cells. As we identified th at one of the antibodies against A549 cells was anti-cytokeratin 8, th e expression of mRNA of cytokeratin 8 in A549 cells was evaluated. In addition, we attempted to establish an enzyme linked immunosorbent ass ay to measure the levels of anti-cytokeratin 8 antibody in the serum o f patients with CFA and pulmonary fibrosis associated with collagen va scular disorders (PF-CVD). Results-Initially two anti-A549 cell antibo dies were detected in the serum of patients with pulmonary fibrosis, o ne of which was characterised as anticytokeratin 8 antibody by Western immunoblotting. We were able to establish an ELISA to measure anti-cy tokeratin 8 antibody and found significantly higher levels in patients with CFA and PF-CVD than in normal volunteers, patients with sarcoido sis, pneumonia, and: pulmonary emphysema. Conclusions-One of the anti- A549 cell antibodies in the serum of patients with CFA was against cyt okeratin 8. The serum levels of anti-cytokeratin 8 antibody were incre ased in patients with CFA and PF-CVD. These results suggest that antic ytokeratin 8 antibody may be involved in the process of lung injury in pulmonary fibrosis.