CIRCULATING ANTIBODIES TO LUNG PROTEIN(S) IN PATIENTS WITH CRYPTOGENIC FIBROSING ALVEOLITIS

Background - It has been hypothesised that cryptogenic fibrosing alveo litis has an immunological pathogenesis mediated by T lymphocytes. It is, however, recognised that patients may show dysregulation of the hu moral immune system and that the presence of large numbers of B lympho cytes in open lung biopsies may be associated with a poor prognosis. E vidence of a role for the humoral immune system in the pathogenesis of cryptogenic fibrosing alveolitis has been suggested, but attempts to demonstrate circulating immunoglobulin to antigen within the lung have been inconclusive. Methods - Plasma samples from 22 patients with cry ptogenic fibrosing alveolitis, 22 patients with sarcoidosis, and 17 he althy controls were screened by SDS-PAGE and Western blotting for the presence of autoantibodies to lung proteins derived from cryptogenic f ibrosing alveolitis, sarcoid and control lung tissue, as well as four normal non-pulmonary tissues. Possible site(s) of target protein(s) wi thin the lung tissue were identified by immunohistochemical examinatio n using IgG purified from the plasma of six patients and two controls. Results - Eighteen of the plasma samples from patients with cryptogen ic fibrosing alveolitis had reactive IgG to lung protein(s) in the 70- 90 kDa molecular weight range compared with five of 18 plasma samples from patients with sarcoidosis and one of 17 controls. Plasma from pat ients with cryptogenic fibrosing alveolitis recognised antigen(s) of t he same molecular weight in control and sarcoid lung tissue, but not n on-pulmonary tissues, with a similar frequency. Immunohistochemical st aining of cryptogenic fibrosing alveolitis biopsy material using IgG p urified from plasma samples from patients with cryptogenic fibrosing a lveolitis, but not control samples, revealed fine linear positivity in the lung parenchyma in a pattern suggestive of reaction with alveolar lining cells. The pattern was cytoplasmic/membranous and not nuclear. Conclusions - Patients with cryptogenic fibrosing alveolitis have a h igh frequency of plasma IgG autoantibodies to protein(s) within lung t issue associated with alveolar lining cells. This is believed to be th e site where immunological injury occurs in cryptogenic fibrosing alve olitis, but the significance of these antibodies to the aetiology and pathogenesis is as yet unclear.