The results were compared with Ab responses to the mycobacterial glycolipid cell wall antigen lipoarabinomannan (LAM) and to the proteins malate synthase (MS) and MPT51. We found that the main immunoglobulin (Ig) isotype response to polysaccharides was IgG, predominantly of subclass IgG2. IgG responses to AM were significantly higher for HIV ؊ and HIV ؉ TB cases than for controls (P, <0.0001 and <0.01, respectively); significantly higher for HIV ؊ than for HIV ؉ TB cases (P, <0.01); and significantly higher in sputum smear-positive than smear-negative patients in both HIV ؊ and HIV ؉ cases (P, 0.01 and 0.02, respectively). In both TB groups, titers of Ab to glucan were significantly lower than titers of Ab to AM (P, <0.0001). IgG responses to AM and MS or to AM and MPT51 did not correlate with each other in HIV ؊ TB patients, while they correlated significantly in HIV ؉ TB patients (P, 0.01 and 0.05, respectively). We conclude that Ab responses to AM could contribute to the serodiagnosis of TB, especially for HIV ؊ TB patients. This study also provides new and important insights into the differences in the profiles of Abs to mycobacterial antigens between HIV ؊ and HIV ؉ TB patients. New biomarkers for the diagnosis of active tuberculosis (TB) are urgently needed. Despite a history of disappointing results, antibodies (Abs) to Mycobacterium tuberculosis antigens remain attractive biomarkers for TB. Detection of serum Abs to M. tuberculosis antigens (serology) does not require a specimen from the site of disease, and tests could easily be developed into a simple, rapid dipstick format. However, commercially available serodiagnostic tests to date have been limited by a lack of sensitivity and specificity (51; reviewed in references 45 and 46). Therefore, the World Health Organization (WHO) recently cautioned against the use of such tests, while strongly recommending further targeted research in the field of TB serology (26).Studies show that multiple antigen testing provides higher sensitivities for TB serodiagnostic assays than tests based on single antigens (reviewed in reference 45). Many mycobacterial proteins and a few lipids and glycolipids have been evaluated for their serodiagnostic potential in recent decades, and some promising antigens have been identified (reviewed in reference 44). However, polysaccharide antigens have been insufficiently studied. Recent studies have confirmed the existence of a mycobacterial capsule that consists mainly of the polysaccharides glucan (70 to 80%) and arabinomannan (AM) (10 to 20%) and, to a lesser extent, of proteins and glycolipids (8,23,36). Located at the interface between the bacterium and host cells, capsular antigens are involved in mycobacterial pathogenicity (8,13,36,47) and therefore likely elicit host immune responses. Navoa et al. demonstrated that titers of Ab to AM were significantly higher in Indian smearpositive cavitary TB patients (n ϭ 20) than in healthy, tuberculin skin test-negative (TST Ϫ ) controls (n ϭ 17) (27). Ab responses to glucan have been e...

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 ؉ ) 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.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 circulating lymphocytes in response to M. ...

The ability to utilize serum or plasma samples interchangeably is useful for tuberculosis (TB) serology. We demonstrate a strong correlation between antibody titers to several mycobacterial antigens in serum versus plasma from HIV-infected and non-HIV-infected TB and non-TB patients (r ‫؍‬ 0.99 to 0.89; P < 0.0001). Plasma and serum can be used interchangeably in the same antibody detection assays.