Surrogate Marker of Preclinical Tuberculosis in Human Immunodeficiency Virus Infection: Antibodies to an 88‐kDa Secreted Antigen of<i>Mycobacterium tuberculosis</i>

Laal, Suman; Samanich, Karen M.; Sonnenberg, Michael G.; Belisle, John T.; O’Leary, Jeanne; Simberkoff, Michael S.; Zolla‐Pazner, Susan

doi:10.1086/514015

Cited by 52 publications

(50 citation statements)

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“…In the studies most of the polypeptides above 30 kDa showed prominent seroreactivity. It was not surprising to observe greater antibody responses to higher-molecularmass antigens since a direct relationship between molecular mass and antibody response has been reported earlier (8,26,27). To detect possible differences in the specificity of mycobacterial antigens between T lymphocytes from peripheral blood and from the site of infection, we investigated the pleural fluid lymphocyte responses of tuberculous pleurisy patients.…”

Section: Discussionmentioning

confidence: 60%

“…Attempts to screen human immune responses against these narrow-molecular-mass fractions demonstrate that low-molecular-mass proteins are prominently recognized by T lymphocytes (12,20), while high-molecular-mass proteins are the major targets of B lymphocytes and induce humoral immune responses (26,27). In view of the potential of lowmolecular-mass polypeptides to augment protective cell-medi-ated immune responses in humans, we purified 104 polypeptides (bands) from the low-molecular-mass (Ͻ40 kDa) secretory proteome of M. tuberculosis and evaluated them for recognition by leukocytes from the above-mentioned models of human immunity to TB.…”

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confidence: 99%

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Peripheral Blood and Pleural Fluid Mononuclear Cell Responses to Low-Molecular-Mass Secretory Polypeptides ofMycobacterium tuberculosisin Human Models of Immunity to Tuberculosis

et al. 2005

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A total of 104 polypeptides were purified from the low-molecular-mass secretory proteome of Mycobacterium tuberculosis H 37 Rv using a combination of anion exchange column chromatography and high resolution preparative sodium dodecyl sulfate-polyacrylamide gel electrophoresis followed by electroelution. The goal of this study was to identify polypeptides from a low-molecular-mass secretory proteome recognized by human subjects infected with M. tuberculosis and to ascertain the differences in specificity of antigen recognition by the peripheral blood mononuclear cells (PBMCs) and pleural fluid mononuclear cells (PFMCs) of these individuals. The study identified CFP-8 (Rv0496), CFP-11 (Rv2433c), CFP-14.5 (Rv2445c), and CFP-31 (Rv0831c) as novel T-cell antigens apart from previously characterized ESAT-6, TB10.4, CFP10, GroES, MTSP14, MTSP17, CFP21, MPT64, Ag85A, and Ag85B on the basis of recognition by PBMCs of tuberculosis contacts and treated tuberculosis patients. Further, polypeptides prominently recognized by PFMCs of tuberculous pleurisy patients were the same as those recognized by PBMCs of healthy contacts and treated tuberculosis patients. The results of our study indicate the homogeneity of antigenic target recognition by lymphocytes at the site of infection and at the periphery in the human subjects studied and the need to evaluate these antigenic targets as components of future antituberculous vaccines.

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Section: Discussionmentioning

confidence: 60%

mentioning

confidence: 99%

Peripheral Blood and Pleural Fluid Mononuclear Cell Responses to Low-Molecular-Mass Secretory Polypeptides ofMycobacterium tuberculosisin Human Models of Immunity to Tuberculosis

et al. 2005

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“…This suggests that antibodies to this protein are present in M. tuberculosis-infected individuals who have not yet developed the active disease. Recently, Laal et al [33] have also noted that antibodies to several M. tuberculosis-specific proteins could be detected in the sera of human immunodeficiency virus (HIV)-infected individuals long before they developed the active disease. Our findings clearly indicate the potential of the ORF-14 protein for the development of serodiagnostic tools for specific identification of M. tuberculosis infection and for the distinction between BCG-vaccinated and M. tuberculosis-infected individuals.…”

Section: Discussionmentioning

confidence: 99%

Identification of a Novel Protein Antigen Encoded by a Mycobacterium tuberculosis‐Specific RD1 Region Gene

et al. 1999

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A genomic DNA region, designated RD1, that is present in virulent and clinical strains of Mycobacterium tuberculosis and M. bovis, has been shown to be deleted in bacillus Calmette Guérin (BCG). The DNA segments corresponding to three open reading frames (ORFs: ORF‐10, ORF‐14 and ORF‐15) of the RD1 region, that are deleted in BCG strains, were amplified from M. tuberculosis genomic DNA by polymerase chain reaction (PCR), subcloned into pGEX‐4T vector system and expressed in Escherichia coli as fusion proteins with glutathione‐S‐transferase (GST). The recombinant proteins appeared as major cellular proteins in SDS‐PAGE gels at the expected molecular mass. The identity of each fusion protein was confirmed by reactivity with anti‐GST antibodies in Western immunoblots. When pooled human sera from 11 tuberculosis (TB) patients were used as the source of antibodies, only GST‐ORF‐14 fusion protein reacted in Western immunoblots. The protein corresponding to ORF‐14 was then purified to near homogeneity and isolated free of its fusion partner (GST) by treating the purified GST‐ORF‐14 fusion protein with thrombin protease. In Western immunoblots, the purified ORF‐14 protein reacted with antibodies in 26 of 57 human sera (46%) from TB patients while no reactivity was seen with 11 sera from M. bovis BCG‐vaccinated healthy subjects. Interestingly, sera from nine of 15 (60%) long‐term contacts of TB patients also had antibodies reactive to the ORF‐14 protein. These results suggest that the ORF‐14 protein in combination with other immunodominant proteins could be useful in the serodiagnosis of individuals infected with M. tuberculosis.

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“…A study using ES -38 kDa antigen and anti-ES-38 antibodies have been reported primarily in patients with recurrent advanced chronic TB infection [12]. Laal et al [13] have reported the presence of 88 kDa secreted antigen as a surrogate marker for identifying HIV infected persons with active, subclinical disease who are at the higher risk of developing clinical tuberculosis. A study by Kaplan et al [14] showed difference in antibody levels in patients of new and relapse TB cases using crude culture filtrate antigen by immunodiffusion test.…”

Section: Proteins Released By M Tb Bacilli During Growthmentioning

confidence: 99%

Excretory Secretory Proteins Released during Growth of Mycobacterium tuberculosis (H37Ra), With Diagnostic Potential in Pulmonary and Extra Pulmonary Tuberculosis

Waghmare¹,

Wankhade²,

Jena³

et al. 2016

Mycobact Dis

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TB immunodiagnostics based on antibody and antigen detection for early detection and monitoring tubercular infections at low cost and flexible to adapt to field laboratories are a boon to developing countries. In this context we have explored in-house developed penicillinase based ELISA assays for the detection of antigen, antibody as well as immune-complexed antigen using various excretory secretory antigenic proteins and specific antibodies. Excretory secretory protein antigens such as ES-31, ES-41, ES-43, ES-6, ES-20, ES-100 and EST-6 were studied extensively and found to be useful in various pulmonary and extra pulmonary cases of tuberculosis infection. ES-31 has shown its diagnostic potential in chronic PTB cases, ES-43 in relapse cases and ES-41 in bone and joint TB. Elevated level of ES-20 antigen was observed in patients with weak immune response in TB lymphadenitis. Detection of ES-100 antigen and antibody by penicilinase ELISA was observed to be useful in detection of TB meningitis. ES-6 antigen was shown to be useful in detection of latent infection. These proteins with antigenic properties are utilized for production of specific antibodies against them and observed to be useful in immune diagnostics for detection of specific circulating and immune complexed antigens. Further user friendly peroxidase immunoassay has been standardised and is being routinely used for suspected TB cases attending 1000 bedded Kasturba Hospital attached to medical institute on physician's request.

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Surrogate Marker of Preclinical Tuberculosis in Human Immunodeficiency Virus Infection: Antibodies to an 88‐kDa Secreted Antigen ofMycobacterium tuberculosis

Cited by 52 publications

References 1 publication

Peripheral Blood and Pleural Fluid Mononuclear Cell Responses to Low-Molecular-Mass Secretory Polypeptides ofMycobacterium tuberculosisin Human Models of Immunity to Tuberculosis

Peripheral Blood and Pleural Fluid Mononuclear Cell Responses to Low-Molecular-Mass Secretory Polypeptides ofMycobacterium tuberculosisin Human Models of Immunity to Tuberculosis

Identification of a Novel Protein Antigen Encoded by a Mycobacterium tuberculosis‐Specific RD1 Region Gene

Excretory Secretory Proteins Released during Growth of Mycobacterium tuberculosis (H37Ra), With Diagnostic Potential in Pulmonary and Extra Pulmonary Tuberculosis

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