Response of IFN-γ and IgG to ESAT-6 and 38 kDa recombinant proteins and their peptides from Mycobacterium tuberculosis in tuberculosis patients and asymptomatic household contacts may indicate possible early-stage infection in the latter

López-Vidal, Yolanda; León-Rosales, Samuel Ponce de; Castañón-Arreola, Mauricio; Rangel‐Frausto, M. Sigfrido; Meléndez-Herrada, Enrique; Sada-Dı́az, Eduardo

doi:10.1016/j.arcmed.2004.04.008

Cited by 19 publications

(21 citation statements)

References 34 publications

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“…In contrast with the other individual proteins, 38 kDa was the most specific antigen for TST Ϫ controls, displaying the lowest IFN-γ average production (13.9Ϯ5.8 pg/ml, PϽ0.026) and similarly low T cell response for TB patients and TST ϩ controls (Pϭ0.103), corroborating previous results (24). However, the improvement of IFN-γ production with 38 kDa/CFP-10 combination related to the individual antigens in TB patients is evident (Fig.…”

Section: Discussionsupporting

confidence: 79%

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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

Tavares

Salgado

Moreira

et al. 2007

Microbiology and Immunology

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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‐γ 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‐γ production in TB patients was significantly 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‐γ response to 38 kDa/CFP‐10 showed an increased tendency in treated patients, although not significant (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.

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Section: Discussionsupporting

confidence: 79%

“…Several other proteins, such as 38 kDa and MPT-64, have been exploited as diagnostic reagents and vaccine components. In guinea pigs, the combination of ESAT-6/MPT-64 has higher potential as a reagent for a new skin test than ESAT-6 alone (9,19,24,35,36).…”

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confidence: 99%

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

Tavares

Salgado

Moreira

et al. 2007

Microbiology and Immunology

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“…These individuals suffered occupational exposure, and subclinical disease cannot be excluded. Lopez-Vidal et al [36], studying the response to ESAT-6 and 38kDa recombinant proteins in tuberculosis patients and in asymptomatic household contacts, concluded that ESAT-6 recognition by HHC could indicate early-stage infections.…”

Section: Discussionmentioning

confidence: 99%

Combined use of Western blot/ELISA to improve the serological diagnosis of human tuberculosis

Beck¹,

Leite²,

Arruda³

et al. 2005

Braz J Infect Dis

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Two recombinant antigens and a crude bacterial antigen of a wild M. tuberculosis strain were used to detect specific IgG antibodies in sera from 52 patients with pulmonary tuberculosis, confirmed by an acid-fast smear and serum culture of these patients and that of 25 contacts. The patients were not infected with HIV. We evaluated the sensitivity and specificity of ELISA, based on the recombinant TbF6® ® ® ® ® and TbF6/DPEP antigen and a search for reactivity patterns in the Western blot technique, using whole mycobacterium antigen. Serum samples from 22 healthy individuals and from 30 patients with lung diseases other than tuberculosis were used as controls. The best ELISA results were obtained with the TbF6/DPEP antigen combination, which gave 85% sensitivity and 91% specificity. ELISA sensitivity improved from 85% to 92% when the Western blot results were used. Western blot specificity was 100% when antibody reactivity with different antigenic bands was analyzed and associated. The association of TbF6/DPEP antigens used in ELISA with specific patterns of reactivity determined by Western blot can help make an identification when classic methods for the diagnosis of pulmonary tuberculosis are not sufficient.

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“…M. tuberculosis ESAT-6 antigen is small [~100 amino acids (aa), an apparent molecular mass of 6 kDa], highly immunogenic and has been shown to induce antibody production. Therefore, it is plausible that the detection of a humoral response to ESAT-6 may play a fundamental role in the identification of individuals that have been exposed to TB recently and have an increased risk of disease in endemic areas (Harboe 1998, López-Vidal et al 2004. Often, the Ag85c proteins are the most common proteins identified in M. tuberculosis culture supernatants.…”

Section: The Goal Of This Study Was To Demonstrate the Usefulness Of mentioning

confidence: 99%

“…At least eight proteins secreted by M. tuberculosis have been isolated and characterised. Of these proteins, the ESAT-6 and the Ag85 complexes (Ag85c) have been tested to determine their accuracy and consistency for use in a diagnostic assay for TB infection (Wiker & Harboe 1992, López-Vidal et al 2004. M. tuberculosis ESAT-6 antigen is small [~100 amino acids (aa), an apparent molecular mass of 6 kDa], highly immunogenic and has been shown to induce antibody production.…”

Section: The Goal Of This Study Was To Demonstrate the Usefulness Of mentioning

confidence: 99%

Immunologic evaluation and validation of methods using synthetic peptides derived from Mycobacterium tuberculosis for the diagnosis of tuberculosis infection

Araujo¹,

Giampietro²,

Bochichio³

et al. 2013

Mem. Inst. Oswaldo Cruz

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The World Health Organization (WHO) lists tuberculosis (TB) as the most important fatal infection worldwide (WHO 2009). The development of a new diagnostic test for TB infection is an important component of the Global Plan to Stop TB and the WHO Stop TB Strategy. In 2005 alone, an estimated 8.8 million individuals were infected with TB and 1.6 million people died of the disease (WHO 2009). Importantly, less than one half of the total 8.8 million estimated cases were diagnosed as smear-positive; the diagnosis of smear-negative patients has proven to be more challenging. Currently, a definitive diagnosis of both pulmonary TB (PTB) and extrapulmonary TB (EPTB) relies on the time consuming culture of mycobacteria. A vast majority of TB cases occur in developing countries that have limited resources. Rapid, inexpensive diagnostic tests would aid these countries in limiting the spread of infection within their communities (WHO 2009). In addition, molecular methods based on nucleic acid amplification to diagnose TB infection are rapid, highly specific and more sensitive than microscopic examination of smears, but are less sensitive compared to culture assays for smear-negative TB cases (Abebe et al. 2007).Serological tests that rely on the detection of antibodies against Mycobacterium tuberculosis-specific antigens possess several advantages: they are simple, inexpensive and feasible for the diagnosis of TB. Potential M. tuberculosis antigens were recently reviewed in a metaanalysis. A total of 254 studies were identified that encompassed nine native proteins, 27 recombinant proteins, 15 lipid-derived antigens and 30 combination antigen targets. These results indicated that highly specific tests frequently exhibited poor sensitivity, which limited the use of these antigens when a single antigen was used in the assay (Steingart et al. 2009). Recently, there has been renewed interest in the development of antibody-based diagnostic assays that utilise multiple antigens to achieve high sensitivity and specificity (Abebe et al. 2007). Many attempts to develop a serologic TB test have been made. These assays need to discriminate active from latent infection, avoid cross-reactivity with Bacillus Calmette-

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Response of IFN-γ and IgG to ESAT-6 and 38 kDa recombinant proteins and their peptides from Mycobacterium tuberculosis in tuberculosis patients and asymptomatic household contacts may indicate possible early-stage infection in the latter

Cited by 19 publications

References 34 publications

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

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

Combined use of Western blot/ELISA to improve the serological diagnosis of human tuberculosis

Immunologic evaluation and validation of methods using synthetic peptides derived from Mycobacterium tuberculosis for the diagnosis of tuberculosis infection

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