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

Autor: Susanne Burger, Suman Laal, Eric Leibert, Patrick W. Bilder, Steven C. Almo, Elisabeth Jenny-Avital, Jacqueline M. Achkar, Arturo Casadevall, Xian Yu
Rok vydání: 2010
Předmět:
Zdroj: Clinical and Vaccine Immunology. 17:384-392
ISSN: 1556-679X
1556-6811
Popis: 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 wellcharacterized control groups. TB suspects were diagnosed with TB (n 87; 49% sputum microscopy negative, 20% HIV )o r 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. The detection and treatment of individuals who are at early stages of active pulmonary tuberculosis (TB) is critical for the successful control and elimination of TB (34, 38). Mycobacterium tuberculosis is a slow-growing pathogen, and it takes months to years for an infection (and, presumably, reactivation) to progress to clinical TB. In resource-limited countries, the microscopic examination of smears made directly from unprocessed sputum are used for diagnosis, resulting in the identification of only advanced TB patients with high bacillary burden. In contrast, in industrialized settings the combined use of the fluorescence microscopy of decontaminated and concentrated sputum, mycobacterial culture, and nucleic acid amplification technologies permits the identification of patients with much lower bacillary burden and, thus, in the early stages of TB. Still, only around 50% of TB cases are rapidly diagnosed by optimized microscopy (5, 18). While adjunctive amplification methods increase the yield of confirmed TB, albeit with added cost and delays, around 20% of TB cases remain without microbiologic confirmation (5, 18). Additional tests that can enhance the rapid identification of patients at early stages of TB are required to add to the armamentarium of TB diagnostic tests. The amplification power of immune responses potentially can detect TB at a low antigen threshold and without requiring a specimen from the site of infection. Assays that detect TB infection by measuring the gamma interferon release of circulat
Databáze: OpenAIRE