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: 2.47). 03/2010; 17(3):372-5. DOI: 10.1128/CVI.00287-09
Source: PubMed


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.

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    • "Rv2241 was the most immunogenic protein studied, with some potential in terms of practical application as biomarker. Interestingly, Rv2241 is a secreted protein, a feature that has been previously highlighted regarding humoral immune responses in human TB [21] [22] [23] [24] "
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    • "A range of known antigens has been tested for immunogenicity as mixtures, fusion proteins and peptides. These include chimeric Ag85B/ESAT6 with adjuvants monophosphoryl lipid A (MPL) and trehalose 6,6'-dimycolate,15 hsp16.3 with dimethyl-dioctadecyl-ammonium bromide/MPL (DDA/MPL) adjuvant,16 fusion protein M. tuberculosis protein 64 (MPT64)–ESAT6,17 resuscitation-promoting factor B (Rv1009),18 or CFP10, ESAT6 or RpfE (Rv2450) with nitrocellulose,19,20 or Rv377221 and Rv342522 with incomplete Freund's adjuvant; or Ag85B/MPT64190–198/Mtb8.4 plus a novel adjuvant of DDA with BCG extract.23 In-silico analysis of putative MHC Class 1-restricted epitopes present in antigens encoded within the region of difference 1 (RD-1) to RD-16 regions of M. bovis genome has revealed potential high-affinity HLA binders24 and profiles of human humoral responses to 38-kDa, MTB48, CFP10/ESAT6 antigens have been defined.25 Screening of human immune sera against an expression library of M. tuberculosis open reading frames revealed three novel antigens among the top 20 most strongly recognized: Rv1987, Rv3807c and Rv3887c.26 "
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    • "Approximately 90% of patients produce antibodies to Mtb proteins with antibody profiles showing great inter-individual variation. So far, a clear correlation between antibody profiles and disease status has not been clearly established, making its use for routine diagnostics problematic (Lyashchenko et al., 1998; Wu et al., 2010). Recently, a major contribution to the field has been published by Kunnath-Velayudhan and colleagues (Kunnath-Velayudhan et al., 2010). "

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