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Title: Autoantibodies to a pulmonary epithelial antigen in cryptogenic fibrosing alveolitis
Author: Wallace, William Andrew Hamilton
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 1995
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Studies presented in this thesis have shown for the first time that patients with CFA have a high incidence (>80%) of circulating IgG autoantibodies to an antigen present in lung tissue. The antigen appears to be endogenous, being detectable in CFA, sarcoid and control lung tissue. Experiments conducted with IgG purified from patient plasma suggested that the antigen was associated with alveolar epithelial lining cells. An antiserum to this antigen raised in a rabbit was shown to recognise the same antigen as the patient autoantibody using a series of absorption, immunoprecipitation and antigen capture experiments. Immunohistochemistry revealed that this antigen was associated with alveolar epithelial lining cells and appeared to be lung specific. Experiments using the rabbit antiserum and CFA patient plasma revealed that the same antigen was expressed in an alveolar epithelial cell line (A549). Studies conducted with these cells demonstrated that the antigen was intracellular and appeared associated with the microsomal compartment of the cell although its nature remains unknown. Despite this apparent intracellular location the antigen was detected in bronchoalveolar lavage samples from some patients with CFA. In vitro experiments culturing the A549 cells in the presence of the immune rabbit sera revealed an inhibitory effect on cell number suggesting some biological activity for the anti-sera. The data presented in this thesis confirms that a humoral immune response is occurring in the lungs of patients with CFA to an alveolar epithelial cell antigen. The presence of this autoantibody raises the possibility of developing a serological test for the diagnosis and/or monitoring of disease activity in CFA.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available