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Pathophysiology of Antigen 85 in Patients with Active Tuberculosis: Antigen 85 Circulates as Complexes with Fibronectin and Immunoglobulin G
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| Zeitschriftentitel: | Infection and Immunity |
|---|---|
| Personen und Körperschaften: | , , , , |
| In: | Infection and Immunity, 67, 1999, 2, S. 581-588 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
American Society for Microbiology
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| Schlagwörter: |
| author_facet |
Bentley-Hibbert, Stuart I. Quan, Xin Newman, Thomas Huygen, Kris Godfrey, Henry P. Bentley-Hibbert, Stuart I. Quan, Xin Newman, Thomas Huygen, Kris Godfrey, Henry P. |
|---|---|
| author |
Bentley-Hibbert, Stuart I. Quan, Xin Newman, Thomas Huygen, Kris Godfrey, Henry P. |
| spellingShingle |
Bentley-Hibbert, Stuart I. Quan, Xin Newman, Thomas Huygen, Kris Godfrey, Henry P. Infection and Immunity Pathophysiology of Antigen 85 in Patients with Active Tuberculosis: Antigen 85 Circulates as Complexes with Fibronectin and Immunoglobulin G Infectious Diseases Immunology Microbiology Parasitology |
| author_sort |
bentley-hibbert, stuart i. |
| spelling |
Bentley-Hibbert, Stuart I. Quan, Xin Newman, Thomas Huygen, Kris Godfrey, Henry P. 0019-9567 1098-5522 American Society for Microbiology Infectious Diseases Immunology Microbiology Parasitology http://dx.doi.org/10.1128/iai.67.2.581-588.1999 <jats:title>ABSTRACT</jats:title><jats:p>Antigen 85 (Ag85) complex proteins are major secretory products of<jats:italic>Mycobacterium tuberculosis</jats:italic>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<jats:italic>M. avium-intracellulare</jats:italic>disease or other nontuberculous pulmonary disease or in healthy controls (<jats:italic>P</jats:italic>< 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<jats:italic>M. avium</jats:italic>disease could be distinguished from those with disease due to<jats:italic>M. tuberculosis</jats:italic>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.</jats:p> Pathophysiology of Antigen 85 in Patients with Active Tuberculosis: Antigen 85 Circulates as Complexes with Fibronectin and Immunoglobulin G Infection and Immunity |
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American Society for Microbiology, 1999 |
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| title |
Pathophysiology of Antigen 85 in Patients with Active Tuberculosis: Antigen 85 Circulates as Complexes with Fibronectin and Immunoglobulin G |
| title_unstemmed |
Pathophysiology of Antigen 85 in Patients with Active Tuberculosis: Antigen 85 Circulates as Complexes with Fibronectin and Immunoglobulin G |
| title_full |
Pathophysiology of Antigen 85 in Patients with Active Tuberculosis: Antigen 85 Circulates as Complexes with Fibronectin and Immunoglobulin G |
| title_fullStr |
Pathophysiology of Antigen 85 in Patients with Active Tuberculosis: Antigen 85 Circulates as Complexes with Fibronectin and Immunoglobulin G |
| title_full_unstemmed |
Pathophysiology of Antigen 85 in Patients with Active Tuberculosis: Antigen 85 Circulates as Complexes with Fibronectin and Immunoglobulin G |
| title_short |
Pathophysiology of Antigen 85 in Patients with Active Tuberculosis: Antigen 85 Circulates as Complexes with Fibronectin and Immunoglobulin G |
| title_sort |
pathophysiology of antigen 85 in patients with active tuberculosis: antigen 85 circulates as complexes with fibronectin and immunoglobulin g |
| topic |
Infectious Diseases Immunology Microbiology Parasitology |
| url |
http://dx.doi.org/10.1128/iai.67.2.581-588.1999 |
| publishDate |
1999 |
| physical |
581-588 |
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<jats:title>ABSTRACT</jats:title><jats:p>Antigen 85 (Ag85) complex proteins are major secretory products of<jats:italic>Mycobacterium tuberculosis</jats:italic>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<jats:italic>M. avium-intracellulare</jats:italic>disease or other nontuberculous pulmonary disease or in healthy controls (<jats:italic>P</jats:italic>< 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<jats:italic>M. avium</jats:italic>disease could be distinguished from those with disease due to<jats:italic>M. tuberculosis</jats:italic>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.</jats:p> |
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| author | Bentley-Hibbert, Stuart I., Quan, Xin, Newman, Thomas, Huygen, Kris, Godfrey, Henry P. |
| author_facet | Bentley-Hibbert, Stuart I., Quan, Xin, Newman, Thomas, Huygen, Kris, Godfrey, Henry P., Bentley-Hibbert, Stuart I., Quan, Xin, Newman, Thomas, Huygen, Kris, Godfrey, Henry P. |
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| description | <jats:title>ABSTRACT</jats:title><jats:p>Antigen 85 (Ag85) complex proteins are major secretory products of<jats:italic>Mycobacterium tuberculosis</jats:italic>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<jats:italic>M. avium-intracellulare</jats:italic>disease or other nontuberculous pulmonary disease or in healthy controls (<jats:italic>P</jats:italic>< 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<jats:italic>M. avium</jats:italic>disease could be distinguished from those with disease due to<jats:italic>M. tuberculosis</jats:italic>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.</jats:p> |
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| spelling | Bentley-Hibbert, Stuart I. Quan, Xin Newman, Thomas Huygen, Kris Godfrey, Henry P. 0019-9567 1098-5522 American Society for Microbiology Infectious Diseases Immunology Microbiology Parasitology http://dx.doi.org/10.1128/iai.67.2.581-588.1999 <jats:title>ABSTRACT</jats:title><jats:p>Antigen 85 (Ag85) complex proteins are major secretory products of<jats:italic>Mycobacterium tuberculosis</jats:italic>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<jats:italic>M. avium-intracellulare</jats:italic>disease or other nontuberculous pulmonary disease or in healthy controls (<jats:italic>P</jats:italic>< 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<jats:italic>M. avium</jats:italic>disease could be distinguished from those with disease due to<jats:italic>M. tuberculosis</jats:italic>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.</jats:p> Pathophysiology of Antigen 85 in Patients with Active Tuberculosis: Antigen 85 Circulates as Complexes with Fibronectin and Immunoglobulin G Infection and Immunity |
| spellingShingle | Bentley-Hibbert, Stuart I., Quan, Xin, Newman, Thomas, Huygen, Kris, Godfrey, Henry P., Infection and Immunity, Pathophysiology of Antigen 85 in Patients with Active Tuberculosis: Antigen 85 Circulates as Complexes with Fibronectin and Immunoglobulin G, Infectious Diseases, Immunology, Microbiology, Parasitology |
| title | Pathophysiology of Antigen 85 in Patients with Active Tuberculosis: Antigen 85 Circulates as Complexes with Fibronectin and Immunoglobulin G |
| title_full | Pathophysiology of Antigen 85 in Patients with Active Tuberculosis: Antigen 85 Circulates as Complexes with Fibronectin and Immunoglobulin G |
| title_fullStr | Pathophysiology of Antigen 85 in Patients with Active Tuberculosis: Antigen 85 Circulates as Complexes with Fibronectin and Immunoglobulin G |
| title_full_unstemmed | Pathophysiology of Antigen 85 in Patients with Active Tuberculosis: Antigen 85 Circulates as Complexes with Fibronectin and Immunoglobulin G |
| title_short | Pathophysiology of Antigen 85 in Patients with Active Tuberculosis: Antigen 85 Circulates as Complexes with Fibronectin and Immunoglobulin G |
| title_sort | pathophysiology of antigen 85 in patients with active tuberculosis: antigen 85 circulates as complexes with fibronectin and immunoglobulin g |
| title_unstemmed | Pathophysiology of Antigen 85 in Patients with Active Tuberculosis: Antigen 85 Circulates as Complexes with Fibronectin and Immunoglobulin G |
| topic | Infectious Diseases, Immunology, Microbiology, Parasitology |
| url | http://dx.doi.org/10.1128/iai.67.2.581-588.1999 |