Tuberculosis (TB), caused by Mycobacterium tuberculosis, is currently on the rise as a result of reactivation of previously acquired mycobacterial disease in patients with HIV infection and AIDS. Patients infected with M. tuberculosis develop cellular immunity and delayed hypersensitivity to mycobacterial antigens. Delayed skin reactivity to purified protein derivative of tuberculin (PPD), particularly among people not immunized to mycobacterial antigens by vaccination with M. bovis BCG, serves as an important diagnostic tool in the United States. Unfortunately, reactivity to PPD is frequently lacking in patients with active TB even in the absence of HIV-related immunodeficiency. This lack of reactivity in an appreciable number of TB patients makes it important to identify other antigens which accurately and rapidly indicate active mycobacterial infection and which do not depend on integrity of host immune response. As part of our long-term interest in clarifying biochemical and immunologic roles of mycobacterial antigens in the pathogenesis of TB, we have identified antigens which may predict active disease. Mycobacterial proteins of the antigen 85 (Ag85) complex are major secretory proteins of M. tuberculosis. Our preliminary data suggest that these 30-32 kDa proteins can be readily detected in sera from some patients with active TB who are skin test negative. This in turn suggests that the presence of Ag85 proteins in the circulation may predict active mycobacterial infection. This hypothesis will be tested using an immunoassay based on mouse monoclonal anti-Ag85 recognizing species-specific and cross-reacting epitopes of M. tuberculosis Ag85 to measure levels of circulating Ag85 in HIV-infected and non-infected people with and without TB. Measured levels of Ag85 will be correlated with results of bacteriologic culture, PPD skin test reactivity and other clinical parameters.
