1/21. Abnormal immunological response to mycobacterium tuberculosis antigens in a patient with chronic myelocytic leukemia and active tuberculosis.The pathogenic mechanisms of immunosuppression leading to susceptibility of mycobacterium tuberculosis (MT) infection in chronic myelocytic leukemia (CML) are not clear. To address this issue, we measured the proliferative response, variation of T cell subpopulations (CD4 , CD8 , TCR-V delta 2 and TCR-V beta 8 T cells) and the cytokine profile (IL-1 beta, IL-2, IL-4, IL-6, IL-10, TNF-alpha, IFN-gamma) after MT stimulation of peripheral blood mononuclear cells (PBMC) in a patient with concomitant CML and active pulmonary tuberculosis. The results were compared to four patients with active pulmonary tuberculosis and no other coexistent diseases. The immunologic response to phytohemagglutinin (PHA) was also evaluated. In contrast to controls, the CML PBMC failed to proliferate in response to MT antigens. Mycobacterium-reactive CD4 , V delta 2 and V beta 8 T cells did not expand after MT stimulation of the CML PBMC. In MT antigens-stimulated cultures from the CML patient, IL-2 was not produced and mild reduction of IL-1 beta and INF-gamma were observed. In contrast, IL-10 was markedly elevated in these cultures. Similarly, PHA-stimulated PBMC from the CML patient showed no expansion of CD4 and CD8 . T cells. In these cell cultures, INF-gamma concentration in supernatants was decreased and IL-10 was significantly elevated. This study suggests that patients with CML may present a profound immunosuppression of essential cellular and molecular immune effectors, a scenario which might contribute to the development of active tuberculosis. These findings further support the need of establishing immunotherapeutic modalities with potential value for myeloproliferative disorders.- - - - - - - - - - ranking = 1keywords = antigen (Clic here for more details about this article) |
2/21. Uncommon presentations of tuberculosis: the potential value of a novel diagnostic assay based on the mycobacterium tuberculosis-specific antigens ESAT-6 and CFP-10.SETTING: Leiden University Medical Center, Leiden, the netherlands. OBJECTIVE: To illustrate the potential value of a recently developed diagnostic assay for detection of tuberculosis (TB), based on T cell responses to the early secreted antigenic target 6 kDa protein (ESAT-6) and culture filtrate protein 10 (CFP-10). These antigens are mycobacterium tuberculosis specific because they are expressed by M. tuberculosis but absent from M. bovis bacille Calmette-Guerin (BCG) and most environmental mycobacteria. In recent studies, the assay had a high sensitivity and specificity for detection of active TB. DESIGN: We describe five patients with uncommon presentations of tuberculosis, in whom the diagnosis was delayed by negative or conflicting results of diagnostic procedures aimed at detection of M. tuberculosis and an uninformative tuberculin skin test. IFN-gamma production in response to ESAT-6 and CFP-10 by peripheral blood mononuclear cells from these patients was evaluated before and during anti-tuberculosis treatment. RESULTS: In all five patients, IFN-gamma responses to ESAT-6 and/or CFP-10 were above the cut-off level defined in a previous study. During treatment, IFN-gamma responses generally increased. CONCLUSION: These results indicate that T cell responses to M. tuberculosis-specific antigens have potential diagnostic value when TB is suspected and the results of other diagnostic tests are inconclusive, especially in BCG-vaccinated individuals.- - - - - - - - - - ranking = 1.1666666666667keywords = antigen (Clic here for more details about this article) |
3/21. Failure of commercial ligase chain reaction to detect mycobacterium tuberculosis dna in sputum samples from a patient with smear-positive pulmonary tuberculosis due to a deletion of the target region.We report on a strain of mycobacterium tuberculosis with a deletion in the protein antigen B gene overlapping the probe binding sites for the Abbott Diagnostics LCx M. tuberculosis (LCx-MTB) probe assay. A false-negative result with the LCx-MTB assay delayed a laboratory diagnosis of tuberculosis.- - - - - - - - - - ranking = 0.16666666666667keywords = antigen (Clic here for more details about this article) |
4/21. American cutaneous leishmaniasis, lepromatous leprosy, and pulmonary tuberculosis coinfection with downregulation of the T-helper 1 cell response.Cutaneous leishmaniasis, leprosy, and tuberculosis are caused by intracellular pathogens whose development depends on impaired cell-mediated immunity. We report an exceptional triple association of American cutaneous leishmaniasis, lepromatous leprosy, and pulmonary tuberculosis in a man with no recognized immunodeficiency. Normal immunological assessment of the interferon-gamma pathway does not support the hypothesis of a genetic defect in any of the genes involved in the T helper (Th)-1 cytokine cascade in this patient. Unresponsiveness to interleukin (IL)-12 of his T cells after stimulation with leishmania guyanensis, mycobacterium bovis bacille Calmette-Guerin, and mycobacterium leprae antigens suggested the inability to mount an appropriate Th cell response to upregulate the IL-12 receptor expression.- - - - - - - - - - ranking = 0.16666666666667keywords = antigen (Clic here for more details about this article) |
5/21. Extrapulmonary small-cell carcinoma of the liver.A 53-year-old man was admitted to our hospital for the evaluation of a mass (13 x 10 cm) in the left lobe of the liver seen by imaging studies. On subsequent biopsy of the mass, the lesion was histologically diagnosed as malignant small round-cell tumor, consistent with metastatic small-cell carcinoma. Segment IV segmentectomy was performed. On pathological examination, the mass showed a yellowish-gray granular appearance with multifocal hemorrhage and necrosis. The phenotypes shown by immunohistochemistry revealed characteristic patterns of small-cell carcinoma (neuron-specific enolase [NSE] , synaptophysin , c-Kit , cluster designation [CD]56 , epithelial membrane antigen [EMA] , cytokeratin [CK]7-). High resolution-computed tomography (HRCT) revealed inactive pulmonary tuberculosis with small calcified tuberculoma in the right upper lobe. sputum cytology was negative for malignancy. The postoperative course was uneventful, and platinum-based chemotherapy (cisplatin, etoposide) was initiated.- - - - - - - - - - ranking = 0.16666666666667keywords = antigen (Clic here for more details about this article) |
6/21. Transmission of mycobacterium tuberculosis undetected by tuberculin skin testing.RATIONALE: The development of tuberculin skin test (TST) positivity following infection by mycobacterium tuberculosis is not invariable and may depend on bacillary as well as host factors. OBJECTIVES: First, to compare the diagnostic performance of the TST and a form of in vitro IFN-gamma release assay (IFNGRA) in the circumstances of a contact investigation prompted by an unusually severe index case of infectious pulmonary tuberculosis. Second, to investigate the ability of the strain of M. tuberculosis responsible to induce cytokine secretion from monocytes in vitro. methods: A routine TST-based tuberculosis-contact screening procedure supplemented by the use of an "in house" IFNGRA that assays the T-cell response to the M. tuberculosis-specific antigens ESAT-6, CFP-10 (presented as a fusion protein within the inactivated adenylate cyclase of bordetella pertussis), and purified protein derivative of M. tuberculosis. Isolation and genetic typing of the strain of M. tuberculosis responsible, and investigation of its ability to induce cytokine secretion from monocytes in vitro. MEASUREMENTS AND MAIN RESULTS: TST screening suggested a low rate of transmission with just 2/75 unequivocally positive responses. By contrast, the IFNGRA suggested an infection rate of 16/75 (22%). When compared with two reference strains of M. tuberculosis (H37Rv and CDC1551), the outbreak strain induced lower levels of tumor necrosis factor-alpha and interleukin-12p40 (p < 0.04), cytokines associated with the development of delayed-type hypersensitivity. CONCLUSIONS: These data suggest that infection by M. tuberculosis can be undetected by TST, and that this may partially relate to strain differences in immunogenicity.- - - - - - - - - - ranking = 0.16666666666667keywords = antigen (Clic here for more details about this article) |
7/21. Detection of mannophosphoinositide antigens in sputum of tuberculosis patients by dot enzyme immunoassay.A simple and economical dot ELISA for the detection of mannophosphoinositide antigen in sputum samples of tuberculosis patients has been developed using affinity-purified antibodies. This test is able to detect free as well as bound antigen. sputum samples from 94 patients suffering from tuberculosis and 30 non-tuberculosis patients were screened and an overall sensitivity and specificity of 89% and 93.3%, respectively, was obtained. The sensitivity of the test among the different groups of tuberculosis patients did not vary significantly.- - - - - - - - - - ranking = 1keywords = antigen (Clic here for more details about this article) |
8/21. Early detection of perinatal tuberculosis using a whole blood interferon-gamma release assay.BACKGROUND: The diagnosis of perinatal tuberculosis (TB) is problematic because of its nonspecific presentation, the difficulty of obtaining microbiological confirmation, and the unreliability of the tuberculin skin test. Immunodiagnosis of TB has received new attention with the discovery of mycobacterium tuberculosis-specific immunodominant antigens (early secreted antigenic target 6 [ESAT-6] and culture filtrate protein 10 [CFP-10]) that are encoded by the RD1 region of the pathogen. A whole blood assay has recently been developed to quantitatively measure interferon- gamma production by lymphocytes specific to these antigens, but its evaluation in the diagnosis of TB in infants and children has been limited to date. methods: In addition to routine diagnostic evaluation (tuberculin skin tests, culture of early-morning gastric aspirate samples, and chest radiographs), 2 infants with suspected perinatal TB were investigated with a whole blood interferon-gamma release assay. RESULTS: The results of the tuberculin skin tests were negative for both patients. The findings of the chest radiographs were abnormal with features suggestive of miliary TB. A whole blood interferon- gamma release assay was performed and yielded positive results within 48 h after admission to the hospital for both patients, prompting early antituberculous treatment. M. tuberculosis was cultured after 6 weeks from gastric aspirate samples collected on admission to the hospital from both infants. At 6 months of age, both infants were thriving and had acheived normal developmental milestones. CONCLUSIONS: The advent of interferon- gamma release assays may prove to be useful in the evaluation of infants with suspected perinatal TB.- - - - - - - - - - ranking = 0.5keywords = antigen (Clic here for more details about this article) |
9/21. Cutaneous tuberculosis and phlyctenular keratoconjunctivitis: a forgotten association.Cutaneous tuberculosis may be associated with concurrent systemic foci in the body such as lung, lymph node, bone or CNS. Phlyctenular keratoconjunctivitis (PKC) is a manifestation of immunological response to a variety of antigens in the eye, tubercular focus (evident or occult) being the commonest in india. Reports in the existing literature have shown lungs and lymph nodes to be the predominant underlying focus associated with PKC, whereas cutaneous tuberculosis has seldom been found in this situation. We report this forgotten association in two children with cutaneous tuberculosis, one each with lupus vulgaris and scrofuloderma, who also had PKC. Interestingly, one of the cases also had simultaneous lichen scrofulosorum, which is also an immunological response to tubercular antigen and manifests in the skin, thus showing immunological manifestation in two different organ systems along with cutaneous focus of tuberculosis.- - - - - - - - - - ranking = 0.33333333333333keywords = antigen (Clic here for more details about this article) |
10/21. Detection by ELISA of specific IgG to mycobacterial antigen 60 in a tuberculous exudate.A case of active multicavitary tuberculosis is reported. In the 3rd month of treatment, an x-ray film of the thorax showed right pleural effusion. The properties of the pleural fluid were those of an exudate with high adenosine deaminase activity. An ELISA was performed to detect specific IgG antibody to mycobacterial antigen 60 in serum before the treatment and on a two-monthly basis following the initiation of therapy until completion of the course. Values were all above 1,750 U. Moreover, an ELISA test using the same antigen was done on pleural fluid, and a high IgG titer was obtained (950 U). A cutoff for a positive ELISA test was established at 240 U in serum and 150 U in other biologic fluids.- - - - - - - - - - ranking = 1keywords = antigen (Clic here for more details about this article) |
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