In this project the following four areas of investigation are outlined: (1) to assess and quantitate the morphological and functional damage produced in the choroid plexus (CP) by immune complexes (IC) and anti-tissue mechanisms of immunopathologic injury; (2) to evaluate the frequency of CP damage and its relationship to CNS abnormalities in human autoimmune anti-basement membrane antibody disease (ABMAbD), Goodpasture's syndrome; (3) to make an assessment of the factors which render the CP and other vascular beds such as the lung susceptible to direct antibody attack; (4) to evaluate the role of molecular mimicry in establishing autoimmune responses which can damage tissue. These studies will focus on factors which affect vascular permeability and thereby permit antibody accumulation to occur. Age-related factors which may influence the susceptibility to attack will be evaluated since the clinical features of patients with ABMAbD vary with age. This work will involve the development of assays to detect cross-reactions of monoclonal antibodies, particularly anti-viral, with tissue antigens in the antigenically complex basement membrane-containing walls of the glo-merular, alveolar and CP capillaries.
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