Article

Humoral immune responses against the Mycobacterium tuberculosis 38-kilodalton, MTB48, and CFP-10/ESAT-6 antigens in tuberculosis.

Institute for Tuberculosis Research, 309th Hospital of Chinese PLA, Beijing 100091, China.
Clinical and vaccine Immunology: CVI (Impact Factor: 2.6). 03/2010; 17(3):372-5. DOI: 10.1128/CVI.00287-09
Source: PubMed

ABSTRACT The diagnosis of smear-negative and culture-negative patients with active tuberculosis (TB) is challenging. The detection of Mycobacterium tuberculosis-specific antibodies in human sera has been an important diagnostic aid. However, detection of antibody responses to a single antigen usually has a low sensitivity for diagnosis of TB. In this study, humoral immune responses against recombinant M. tuberculosis 38-kDa, MTB48, and CFP-10/ESAT-6 (culture filtrate protein 10/6-kDa early secreted antigen target of M. tuberculosis) antigens in 250 Chinese TB patients and 260 healthy subjects were evaluated by an enzyme-linked immunosorbent assay (ELISA). The levels of antibodies against those antigens in TB patients, even in bacterium-negative ones, were significantly higher than those in healthy subjects (P < 0.001). The serodiagnostic sensitivities to detect antibodies against individual antigens, i.e., recombinant M. tuberculosis 38-kDa, MTB48, and CFP-10/ESAT-6 antigens, in TB patients were 73.6%, 73.2%, and 60.4%, respectively, with specificities of 85.4%, 77.7%, and 73.8%, respectively. Importantly, the sensitivity to positively detect humoral responses to one of the antigens increased further. Our data suggest that the humoral immune responses to M. tuberculosis antigens in TB patients are heterogeneous. The 38-kDa, MTB48, and CFP-10/ESAT-6 antigens can be used as the cocktail antigens in the serodiagnosis of active TB, especially for smear- or culture-negative TB cases.

0 Bookmarks
 · 
100 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Development of novel diagnostics for tuberculosis has so far been governed by the clinical requirement of improving the detection of patients with paucibacillary forms of the disease. For this aim, serological assays have been evaluated using several antigens, but were found insufficiently sensitive, because antibody production associates with the bacterial load of the disease. Consequently, detection of antibodies against a relatively small number of selected well-defined antigens has a much higher sensitivity for sputum smear-positive pulmonary disease in adult HIV-negative patients. They are the most active in generating and spreading aerosols containing live tubercle bacilli, but their detection is often delayed, thus perpetuating the transmission of the infection and disease in the population. High volume throughput serological screening of clinical suspects with mild clinical symptoms may help to achieve diagnosis earlier, than currently used procedures. Such expanded testing could be done more efficiently in laboratories, than at 'points-of-care' and at a lower cost than other tests. The feasibility of this approach towards reducing the delayed diagnosis of the most infectious cases of pulmonary tuberculosis needs to be ascertained in prospective diagnostic trials, in populations at a high risk. Reducing the transmission of tuberculosis is of key importance for achieving its continued decline and therefore it is proposed, that the aims of serological screening should shift from clinical to public health priorities.
    Tuberculosis (Edinburgh, Scotland) 09/2011; 92(1):31-7. · 2.54 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Old tuberculin (OT) and purified protein derivative (PPD) are widely used for tuberculin skin testing (TST) in diagnosis of tuberculosis (TB) but often yield poor specificity and anergy in reaction. Therefore, it is necessary to develop new serological methods as a possible auxiliary diagnostic method for TB. In this study, we characterized the dynamic antibody responses of 10 purified recombinant antigens, PPD, and OT in rhesus monkeys experimentally infected with Mycobacterium tuberculosis and analyzed the time to antibody detection, antibody levels, and their association with the infectious doses. The antibodies were detected as early as 4 weeks after infection in response to 5 antigens (CFP10, CFP10-ESAT-6, U1, MPT64, and Ag85b). Antibodies against most of the other antigens were detected between 4 and 12 weeks after infection. The levels of antibodies were dose dependant. We further evaluated the serodiagnostic potential of these antigens by using indirect enzyme-linked immunosorbent assay in 71 TST-positive and 90 TST-negative serum samples from monkeys. For all 12 antigens, the median optical density values of TST-positive monkeys were statistically significantly higher than those of TST-negative monkeys (P < 0.001). Among those antigens, Ag85b and CFP10 showed higher diagnostic potential than others. A combination of results from Ag85b, the 38-kDa antigen (Ag38kDa), and Ag14kDa reaches a sensitivity of 95.77%, indicating that these antigens may be ideal cocktails in TB diagnosis.
    Clinical and vaccine Immunology: CVI 12/2011; 18(12):2154-60. · 2.60 Impact Factor
  • Source
    Understanding Tuberculosis - Global Experiences and Innovative Approaches to the Diagnosis, 02/2012; , ISBN: 978-953-307-938-7

Full-text (2 Sources)

View
29 Downloads
Available from
May 28, 2014