Mycobacterium avium Antigenuria in Patients with AIDS and Disseminated M. avium Disease

Sippola, A A; Gillespie, Susan L.; Lewis, Jennifer A.; Daniel, Thomas M.

doi:10.1093/infdis/168.2.466

Cited by 3 publications

(2 citation statements)

References 8 publications

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“…Moreover, high levels of Ag85 antigenemia in tuberculosis patients were not associated with appreciable Ag85 antigenuria. Ag85 is a small enough protein to expect that it would be readily cleared by the kidney from the circulation, much as other small secreted mycobacterial proteins are (36). The discovery that circulating Ag85 in patients with active tuberculosis existed primarily as complexes with fibronectin and IgG provided a reasonable explanation for its low renal clearance.…”

Section: Discussionmentioning

confidence: 99%

“…It has been recognized for some time that mycobacterial growth products are detectable in tissues and tissue fluids of patients with active infections (6,10,29,32,35,36,42). Analysis of the pathophysiological interaction of growth products such as Ag85 with the host has previously focused on analyzing immune responses (16,22,26,38) or the composition of circulating immune complexes (31).…”

Section: Discussionmentioning

confidence: 99%

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Pathophysiology of Antigen 85 in Patients with Active Tuberculosis: Antigen 85 Circulates as Complexes with Fibronectin and Immunoglobulin G

Bentley–Hibbert¹,

Quan²,

Newman³

et al. 1999

Infect. Immun.

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Antigen 85 (Ag85) complex proteins are major secretory products of Mycobacterium tuberculosis and induce strong cellular and humoral immune responses in infected experimental animals and human beings. We have previously shown that nanogram doses of these 30-to 32-kDa fibronectin-binding proteins inhibit local expression of delayed hypersensitivity by a T-cell fibronectin-dependent mechanism. Circulating levels of Ag85 might be expected to be elevated in patients with active tuberculosis and possibly to play a role in systemic anergy in these patients. To test this hypothesis, Ag85 was measured in serum and urine by a monoclonal antibody-based dot immunobinding assay in 56 patients and controls with known skin test reactivity. Median serum Ag85 levels were 50-to 150-fold higher in patients with active tuberculosis than in patients with active M. aviumintracellulare disease or other nontuberculous pulmonary disease or in healthy controls (P < 0.001). The median and range of serum Ag85 in patients with active tuberculosis was not significantly different between skin test-positive and -negative subjects. Patients with active M. avium disease could be distinguished from those with disease due to M. tuberculosis by monoclonal anti-Ag85 antibodies of appropriate specificities. No increases in urinary Ag85 were detected in any patient, regardless of the Ag85 level in serum. Chromatographic analysis and immunoprecipitation studies of serum revealed that Ag85 existed in the serum of these patients complexed to either fibronectin or immunoglobulin G (IgG). Uncomplexed circulating Ag85 was demonstrable in serum from fewer than 20% of patients with active tuberculosis. In patients with active tuberculosis, Ag85 is therefore likely to circulate primarily as complexes with plasma fibronectin and IgG rather than in unbound form. The existence of Ag85 complexes with plasma proteins would account for its lack of urinary clearance.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Pathophysiology of Antigen 85 in Patients with Active Tuberculosis: Antigen 85 Circulates as Complexes with Fibronectin and Immunoglobulin G

Bentley–Hibbert¹,

Quan²,

Newman³

et al. 1999

Infect. Immun.

View full text Add to dashboard Cite

show abstract

Pathophysiology of Antigen 85 in Patients with Active Tuberculosis: Antigen 85 Circulates as Complexes with Fibronectin and Immunoglobulin G

Bentley–Hibbert¹,

Quan²,

Newman

et al. 1999

Infect Immun

View full text Add to dashboard Cite

Antigen 85 (Ag85) complex proteins are major secretory products ofMycobacterium tuberculosis and induce strong cellular and humoral immune responses in infected experimental animals and human beings. We have previously shown that nanogram doses of these 30- to 32-kDa fibronectin-binding proteins inhibit local expression of delayed hypersensitivity by a T-cell fibronectin-dependent mechanism. Circulating levels of Ag85 might be expected to be elevated in patients with active tuberculosis and possibly to play a role in systemic anergy in these patients. To test this hypothesis, Ag85 was measured in serum and urine by a monoclonal antibody-based dot immunobinding assay in 56 patients and controls with known skin test reactivity. Median serum Ag85 levels were 50- to 150-fold higher in patients with active tuberculosis than in patients with active M. avium-intracellulare disease or other nontuberculous pulmonary disease or in healthy controls (P < 0.001). The median and range of serum Ag85 in patients with active tuberculosis was not significantly different between skin test-positive and -negative subjects. Patients with active M. aviumdisease could be distinguished from those with disease due to M. tuberculosis by monoclonal anti-Ag85 antibodies of appropriate specificities. No increases in urinary Ag85 were detected in any patient, regardless of the Ag85 level in serum. Chromatographic analysis and immunoprecipitation studies of serum revealed that Ag85 existed in the serum of these patients complexed to either fibronectin or immunoglobulin G (IgG). Uncomplexed circulating Ag85 was demonstrable in serum from fewer than 20% of patients with active tuberculosis. In patients with active tuberculosis, Ag85 is therefore likely to circulate primarily as complexes with plasma fibronectin and IgG rather than in unbound form. The existence of Ag85 complexes with plasma proteins would account for its lack of urinary clearance.

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The Purification and Immunogenicity of TB-14 Recombinant Protein of Mycobacterium tuberculosis

Song

Kim

et al. 2006

Tuberc Respir Dis

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Background: Culture filtrate proteins secreted by mycobacteria are thought to play an important role in inducing protective immunity and to develop new methods for diagnosing tuberculosis. Methods: A culture filtrate protein of M. avium that was strongly reactive with goat antiserum against M. intracellulare was constructed. Its homologous protein (TB-14) in M. tuberculosis was cloned, expressed and purified. The inductions of IFN-γ stimulated with 10 ㎍ of TB-14 recombinant protein and 10 ㎍ PPD were estimated by using whole bloods from seven PPD (-) subjects, seven PPD (+) healthy volunteers and nine tuberculosis patients. Results: M. avium culture filtrate protein was confirmed as a hypothetical protein that was termed contig 116. A novel 14-kDa recombinant protein (TB-14) of M. tuberculosis was composed of 148 amino acids, including 30 amino acids of the signal peptide, and it showed 78% homology with M. avium. In the PPD (+) healthy volunteers, recombinant TB-14 protein strongly induced the secretion of IFN-γ in whole blood cultures. Conclusion: These results suggest that TB-14 recombinant protein might play an important role in inducing cell-mediated immunity against tuberculosis. Furthermore, TB-14 protein antigen and its antiserum will be available for the development of new diagnostic tools for tuberculosis. (Tuberc Respir Dis 2006; 61: 239-247)

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Mycobacterium avium Antigenuria in Patients with AIDS and Disseminated M. avium Disease

Cited by 3 publications

References 8 publications

Pathophysiology of Antigen 85 in Patients with Active Tuberculosis: Antigen 85 Circulates as Complexes with Fibronectin and Immunoglobulin G

Pathophysiology of Antigen 85 in Patients with Active Tuberculosis: Antigen 85 Circulates as Complexes with Fibronectin and Immunoglobulin G

Pathophysiology of Antigen 85 in Patients with Active Tuberculosis: Antigen 85 Circulates as Complexes with Fibronectin and Immunoglobulin G

The Purification and Immunogenicity of TB-14 Recombinant Protein of Mycobacterium tuberculosis

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