Tuberculosis has re-emerged as a global health threat today. Current tuberculosis diagnosis is too slow in general and unsensitive in HIV burdened populations. Exposure to mycobacterial antigens in a country with a high prevalence of tuberculosis leads to false positive test results. Serodiagnosis would have been ideal, but was hitherto not successful. Mycolic acid (MA) is the major lipid cell wall constituent of Mycobacterium tuberculosis, the etiological agent of this disease. In this study an antibody response to the MA molecules are investigated as a possible surrogate marker for tuberculosis. In previous studies, IgG antibodies to MA in TB infected, HIV seronegative patients were detected in human sera, with promising results. In this study the ELISA results detecting anti-IgG antibodies to MA in TB and HIV co-infected patients showed a low sensitivity and specificity. The study, however, showed that antibodies to MA are prevalent in HIV seropositive patients. The presentation of MA on the CD1 molecule to T cells might explain why anti-MA antibodies are detected in HIV seropositive patients. The properties of anti-mycolic acid antibodies were investigated to explain the low sensitivities and specificities of the ELISA test. An ELISA was done comparing signals to MA and cholesterol as coating antigen. A degree of cross-reactivity of anti-MA antibodies to cholesterol was obtained. In using the IAsys biosensor it was shown that anti-MA antibodies were inhibited with MA and cholesterol as antigens in liposomes with cholesterol as the weaker antigen. An antibody response to MA might prove to be a good surrogate marker for tuberculosis when measured in an IAsys biosensor based serodiagnostic test, where the serodiagnosis does not depend on the detection of high affinity anti-MA antibodies only.
Dissertation (MSc (Biochemistry))--University of Pretoria, 2007.