Antibodies against Immunodominant Antigens of Mycobacterium tuberculosis in Subjects with Suspected Tuberculosis in the United States Compared by HIV Status

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Abstract
The immunodominance of Mycobacterium tuberculosis proteins malate synthase (MS) and MPT51 has been demonstrated in case-control studies with patients from countries in which tuberculosis (TB) is endemic. The value of these antigens for the serodiagnosis of TB now is evaluated in a cross-sectional study of pulmonary TB suspects in the United States diagnosed to have TB, HIV-associated TB, or other respiratory diseases (ORD). Serum antibody reactivity to recombinant purified MS and MPT51 was determined by enzyme-linked immunosorbent assays (ELISAs) of samples from TB suspects and well-characterized control groups. TB suspects were diagnosed with TB ( n = 87; 49% sputum microscopy negative, 20% HIV + ) or ORD ( n = 63; 58% HIV + ). Antibody reactivity to MS and MPT51 was significantly higher in U.S. HIV + /TB samples than in HIV − /TB samples ( P < 0.001), and it was significantly higher in both TB groups than in control groups with latent TB infection ( P < 0.001). Antibody reactivity to both antigens was higher in U.S. HIV + /TB samples than in HIV + /ORD samples ( P = 0.052 for MS, P = 0.001 for MPT51) but not significantly different between HIV − /TB and HIV − /ORD. Among U.S. HIV + TB suspects, a positive anti-MPT51 antibody response was strongly and significantly associated with TB (odds ratio, 11.0; 95% confidence interval, 2.3 to 51.2; P = 0.002). These findings have implications for the adjunctive use of TB serodiagnosis with these antigens in HIV + subjects.

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