Date of Award

1982

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Microbiology and Immunology

College

College of Graduate Studies

First Advisor

Gabriel Virella

Second Advisor

N. M. Burdash

Third Advisor

Robert J. Boackle

Fourth Advisor

Jean-Michel Goust

Fifth Advisor

James M. Powers

Sixth Advisor

Philippe Arnaud

Abstract

The increasing incidence of systemic candidiasis and the difficulties diagnosing the disease on the basis of clinical data and culture results have prompted investigation into immunological methods of diagnosis. Detection of anti-Candida antibodies has proved to be not sufficiently specific for diagnosis of systemic disease since antibodies are frequently found in the normal individual in whom the organism lives as a commensal and in superficially infected individuals. Our project resulted in the development of a new quantitative immunofluorescence assay for quantitation of anti-Candida antibodies which is able to differentiate quite well (p<0.0005) between systemically infected patients and normals or superficially infected patients. We have also investigated the value of purified antigens and have shown that the use of cytoplasmic protein antigens rather than those containing cell wall polysaccharide confers greater specificity on a qualitative test for anti-Candida antibodies but that a carbohydrate-containing antigen is adequate for differentiating systemic disease when a quantitative test is used. Attempts to diagnose systemic candidiasis by detection of circulating antigen have met with varying degrees of success. We were unable to detect antigen by counter-immunoelectrophoresis, a quantitative immunofluorescence inhibition assay, or an ELISA inhibition assay in the sera of rabbits in whom a Candida endocarditis was induced or in the sera of systemically infected patients. One postulated reason for this failure is the presence of the antigen in the form of circulating immune complexes. We have, therefore, investigated the possibility of the existence of complexes containing Candida antigen and antibody in the sera of patients with systemic candidiasis. Using four screening tests, a statistically significant difference (p < 0.05) was found for immune complex levels in a group of patients and a group of normal individuals. Isolation and characterization of immune complex-containing fractions from five patients with candidiasis indicated the presence of anti-Candida antibodies and/or antigen in at least three of them. Therefore, these fungal immune complexes can be assumed to exist and may play a role in the difficulties in detecting circulating antigen and, furthermore, may be involved in the pathogenesis and progression of disseminated candidiasis.

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