Delineation of Human Antibody Responses to Culture Filtrate Antigens of<i>Mycobacterium tuberculosis</i>

Samanich, Karen M.; Belisle, John T.; Sonnenberg, Michael G.; Keen, Marc A.; Zolla‐Pazner, Susan; Laal, Suman

doi:10.1086/314438

Cited by 54 publications

(75 citation statements)

References 12 publications

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“…It has been previously shown that active TB patients display circulating IgG Ab against several Mtb secreted molecules [40,41]. In the present work, we have shown that active TB patients presented high titers of anti-sMTL-13 IgG, a response that decreased following therapy.…”

Section: Discussionsupporting

confidence: 66%

Mycobacterium tuberculosis Rv1419 encodes a secreted 13 kDa lectin with immunological reactivity during human tuberculosis

et al. 2010

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In this study, we have identified a secreted 13 kDa lectin from Mtb (Mtb, Mycobacterium tuberculosis; sMTL-13) by homology search of a non-redundant lectin database. Bioinformatic analysis revealed that sMTL-13 belongs to the ricin-type b-trefoil family of proteins containing a Sec-type signal peptide present in Mtb complex species, but not in nontuberculous mycobacteria. Following heterologous expression of sMTL-13 and generation of an mAb (clone 276.B7/IgG1j), we confirmed that this lectin is present in culture filtrate proteins from Mtb H37Rv, but not in non-tuberculous mycobacteria-derived culture filtrate proteins. In addition, sMTL-13 leads to an increased IFN-c production by PBMC from active tuberculosis (ATB) patients. Furthermore, sera from ATB patients displayed high titers of IgG Ab against sMTL-13, a response found to be decreased following successful antituberculosis therapy. Together, our findings reveal a secreted 13 kDa ricin-like lectin from Mtb, which is immunologically recognized during ATB and could serve as a biomarker of disease treatment.

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Section: Discussionsupporting

confidence: 66%

Mycobacterium tuberculosis Rv1419 encodes a secreted 13 kDa lectin with immunological reactivity during human tuberculosis

et al. 2010

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“…38 kDa, a major protein present in culture filtrates of M. tuberculosis, has been studied extensively (1,17,22). Several studies have shown an association between the presence of anti-38 kDa antibodies and advanced cavitary TB (14,22,75). In smear-positive patients, recombinant 38 kDa yielded a sensitivity of 47% (95% CI, 39 to 55) and a specificity of 94% (95% CI, 86 to 98) (8,27,33,35,37,55,77,81).…”

Section: Resultsmentioning

confidence: 99%

Performance of Purified Antigens for Serodiagnosis of Pulmonary Tuberculosis: a Meta-Analysis

Steingart

Dendukuri

Henry

et al. 2009

Clin Vaccine Immunol

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The failure to diagnose tuberculosis (TB) accurately and rapidly is a key challenge in curbing the epidemic (45,88,116). Sputum microscopy, currently the sole diagnostic test in most areas where TB is endemic, has several limitations; in particular, the sensitivity compared with that of culture is variable (80,97,104,116), multiple patient visits are required (56,93,114), considerable technical training is necessary, and the procedure is labor-intensive (45, 65). Antibody detection tests (serological tests) are used for the diagnosis of many infectious diseases and could potentially improve the means of diagnosis of TB. These tests measure the presence of specific antibodies (most often immunoglobulin G [IgG]) directed against immunodominant antigens of the pathogen in question. Compared with microscopy, antibody detection methods may enable the rapid diagnosis of TB, as these tests have the advantages of speed (results can be available within hours), technological simplicity, and minimal training requirements. In addition, these tests can be adapted to point-of-care formats that can be implemented at lower levels of health services in low-and middle-income countries (21,22,57,65).Efforts to develop antibody detection tests for the diagnosis of TB have been under way for decades, and the performance of these tests has been well described (13,17,22,32,40,47,48,52,60,64,100,107). Several systematic reviews of these tests have been published (discussed below) (28,94,95).First-generation antibody detection tests were based on crude mixtures of constituents and products of Mycobacterium tuberculosis, for example, culture filtrate proteins and purified protein derivative, the preparation used in the tuberculin skin test. Several of these early tests had low specificities, as the tests contained antigens shared among different bacterial species (1,22,48,57). During the past two decades, an increased understanding of humoral immune responses to M. tuberculosis and the new tools of

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“…These data are in the range of those of other studies that examined humoral immunity to recombinant M. tuberculosis proteins, whereby, depending upon the antigen evaluated and its method of production, the sera of 12 to 58% of TB patients were found to contain specific antibodies (38,41). Overall, the available data indicate that the spectrum of M. tuberculosis antigens recognized humorally varies dramatically between patients (41,58). One contributing factor is the expansion of the repertoire of humoral specificities to M. tuberculosis antigens as TB progresses (2,58).…”

Section: Vol 71 2003mentioning

confidence: 99%

TheMycobacterium tuberculosisComplex-Restricted Genecfp32Encodes an Expressed Protein That Is Detectable inTuberculosis Patients and Is Positively Correlated with PulmonaryInterleukin-10

et al. 2003

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Human tuberculosis (TB) is caused by the bacillus Mycobacterium tuberculosis, a subspecies of the M. tuberculosis complex (MTC) of mycobacteria. Postgenomic dissection of the M. tuberculosis proteome is ongoing and critical to furthering our understanding of factors mediating M. tuberculosis pathobiology. Towards this end, a 32-kDa putative glyoxalase in the culture filtrate (CF) of growing M. tuberculosis (originally annotated as Rv0577 and hereafter designated CFP32) was identified, cloned, and characterized. The cfp32 gene is MTC restricted, and the gene product is expressed ex vivo as determined by the respective Southern and Western blot testing of an assortment of mycobacteria. Moreover, the cfp32 gene sequence is conserved within the MTC, as no polymorphisms were found in the tested cfp32 PCR products upon sequence analysis. Western blotting of M. tuberculosis subcellular fractions localized CFP32 predominantly to the CF and cytosolic compartments. Data to support the in vivo expression of CFP32 were provided by the serum recognition of recombinant CFP32 in 32% of TB patients by enzyme-linked immunosorbent assay (ELISA) as well as the direct detection of CFP32 by ELISA in the induced sputum samples from 56% of pulmonary TB patients. Of greatest interest was the observation that, per sample, sputum CFP32 levels (a potential indicator of increasing bacterial burden) correlated with levels of expression in sputum of interleukin-10 (an immunosuppressive cytokine and a putative contributing factor to disease progression) but not levels of gamma interferon (a key cytokine in the protective immune response in TB), as measured by ELISA. Combined, these data suggest that CFP32 serves a necessary biological function(s) in tubercle bacilli and may contribute to the M. tuberculosis pathogenic mechanism. Overall, CFP32 is an attractive target for drug and vaccine design as well as new diagnostic strategies.The Mycobacterium tuberculosis complex (MTC) is a group of highly related pathogenic mycobacteria that include M. tuberculosis, Mycobacterium africanum (subtypes I and II), Mycobacterium bovis (along with the attenuated M. bovis bacillus Calmette-Guérin [BCG] vaccine strain), Mycobacterium bovis subsp. caprae, and Mycobacterium microti (13). The MTC taxon is extraordinary in that its members exhibit a restricted number of fixed single-nucleotide polymorphisms between subspecies but differ from one another by the presence or absence of large chromosomal deletion loci, severity of disease, and mammalian host spectra (13,43,66

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Delineation of Human Antibody Responses to Culture Filtrate Antigens ofMycobacterium tuberculosis

Cited by 54 publications

References 12 publications

Mycobacterium tuberculosis Rv1419 encodes a secreted 13 kDa lectin with immunological reactivity during human tuberculosis

Mycobacterium tuberculosis Rv1419 encodes a secreted 13 kDa lectin with immunological reactivity during human tuberculosis

Performance of Purified Antigens for Serodiagnosis of Pulmonary Tuberculosis: a Meta-Analysis

TheMycobacterium tuberculosisComplex-Restricted Genecfp32Encodes an Expressed Protein That Is Detectable inTuberculosis Patients and Is Positively Correlated with PulmonaryInterleukin-10

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