title: Interferon gamma response to combinations 38 kDa/CFP-10, 38 kDa/MPT-64, ESAT-6/MPT-64 and ESAT-6/CFP-10, each related to a single recombinant protein of Mycobacterium tuberculosis in individuals from tuberculosis endemic areas.
abstract: Several antigens of Mycobacterium tuberculosis have been identified and specificity to one or multiple antigens could determine the distinction between protective and pathogenic host reaction. Therefore T cell immune response to combinations 38 kDa/CFP-10, 38 kDa/MPT-64, ESAT-6/MPT-64 and ESAT-6/CFP-10 (each related to a single protein of Mycobacterium tuberculosis) in individuals from tuberculosis endemic areas have been examined. ELISA was used to detect IFN-gamma production in PBMC priming with single proteins and combinations in a panel of 105 individuals: 38 tuberculosis patients (6 untreated and 32 treated) and 67 healthy controls with tuberculin skin test positive or negative (TST). Brazilian TB patients highly recognized ESAT-6 (66%), but combinations improved response in the following order: ESAT-6/MPT-64 (89%) > ESAT-6/CFP-10 (73%) > 38 kDa/CFP-10 (70%), the last combination showing the highest specificity (TST(/) = 42% and TST(-) = 83%). Average IFN-gamma production in TB patients was signifi-cantly higher for 38 kDa/CFP-10 (P = 0.012) and 38 kDa/MPT-64 (P <0.035), when compared to single antigens. None of the combinations was able to discriminate TB patients from TST(+) controls; however, 38 kDa/CFP-10 displayed a borderline significance (P = 0.053). Similar to the ESAT-6/CFP-10 combination, IFN-gamma response to 38 kDa/CFP-10 showed an increased tendency in treated patients, although not signifi-cant (P = 0.16). We demonstrated for the first time that 38 kDa/CFP-10 had prediction sensitivity for TB patients similar to the ESAT-6/CFP-10 combination and also significant response improvement related to the single proteins with more selective reactivity among TST-positive individuals, which could be of potential interest for diagnostic evaluation for tuberculosis infection.
authors: Department of Mycobacterioses, IOC, FioCruz, Rio de Janeiro, Brazil.
authors: Ricardo C Oliveira
authors: RC
authors: Tavares
authors: Jorge
authors: J
authors: Salgado
authors: Valéria Barbosa
authors: VB
authors: Moreira
authors: Mônica Antonia S
authors: MA
authors: Ferreira
authors: Fernanda C Queiroz
authors: FC
authors: Mello
authors: Janaína W
authors: JW
authors: Leung
authors: Leila de Souza
authors: Lde S
authors: Fonseca
authors: Ralf
authors: R
authors: Spallek
authors: Mahaviir
authors: M
authors: Singh
authors: Maria Helena F
authors: MH
authors: Saad
mesh_terms: D000328:Adult; D000942:Antigens, Bacterial / Q000276:immunology*; D001426:Bacterial Proteins / Q000276:immunology*; D019353:Endemic Diseases; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D011994:Recombinant Proteins / Q000276:immunology; D014374:Tuberculin Test / Q000379:methods; D014376:Tuberculosis / Q000175:diagnosis / Q000453:epidemiology / Q000276:immunology* / Q000382:microbiology
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; C117940:CFP-10 protein, Mycobacterium tuberculosis; C093276:ESAT-6 protein, Mycobacterium tuberculosis; C510537:MPT64 protein, Mycobacterium tuberculosis; D011994:Recombinant Proteins; D007371:Interferon-gamma