Analysis of antibody responses to streptococcal and tissue antigens in patients with acute rheumatic fever

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Publication Type thesis
School or College School of Medicine
Department Pathology
Author Martins, Thomas Bernd
Title Analysis of antibody responses to streptococcal and tissue antigens in patients with acute rheumatic fever
Date 2007-05
Description Acute Rheumatic Fever (ARF) is an autoimmune disease occurring in individuals following untreated group A streptococcal infection believed to be triggered by antibodies to bacterial components that cross-react with human tissues. A multiplexed immunoassay was developed for the simultaneous quantitation of antibodies to nine different streptococcal related antigens including streptolysin O (SLO), DNase B, Collagens I and IV, fibronectin, myosin, group A carbohydrate, M6 protein, and C5 peptidase. Development of the assay involved testing of several different types of microspheres as well serum diluent formulations in an effort to reduce nonspecific binding of antibodies. Optimal coupling conditions for both protein and carbohydrate antigens to the microspheres were also determined. Monoclonal antibodies were used to determine antigen coupling efficiencies and cross-reactive epitopes of the different antigens. The multiplexed assay was then used to quantitate antibody responses in 49 ARF, 58 pharyngitis patients, and age and sex matched controls in samples collected at initial disease onset, and at 4 weeks, 6 months, and 1 year after diagnosis. Through the selection of microspheres and serum diluent, nonspecific antibody binding was reduced by 17%. Different formulations of the coupling buffer were found to greatly influence the efficiency of coupling antigens to the carboxylated microspheres. Monoclonal antibodies against the different antigens demonstrated assay specificity as well as sensitivities of less than 1 ng/ml of antibody. Antibody responses were significantly higher for SLO, DNase B, M6 protein, group A carbohydrate, and the cross-reactive antigens collagen I and myosin in ARF compared to pharyngitis patients (p<0.05). Moreover, we found significantly elevated antibody responses in the ARF patients with rheumatic heart disease (RHD) to fibronectin and collagen I, compared to ARF patients without heart disease. The major differences between the ARF patients with and without carditis appear to be in the immune response to the putative heart valve components, collagen I and fibronectin.
Type Text
Publisher University of Utah
Subject Antigen-Antibody Reactions
Subject MESH Streptococcal Infections; Rheumatic Fever
Dissertation Institution University of Utah
Dissertation Name MS
Language eng
Relation is Version of Digital reproduction of "Analysis of antibody responses to streptococca". Spencer S. Eccles Health Sciences Library. Print version of "Analysis of antibody responses to streptococca" available at J. Willard Marriott Library Special Collection. QR6.5 2007 .M37.
Rights Management © Thomas Bernd Martins.
Format Medium application/pdf
Format Extent 1,078,706 bytes
Identifier undthes,3927
Source Original University of Utah Spencer S. Eccles Health Sciences Library (no longer available)
Master File Extent 1,078,748 bytes
ARK ark:/87278/s6cc12fr
Setname ir_etd
Date Created 2012-04-24
Date Modified 2021-05-06
ID 190634
Reference URL https://collections.lib.utah.edu/ark:/87278/s6cc12fr
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