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Oral tolerization w...
Oral tolerization with peptide 336-351 linked to cholera toxin B subunit in preventing relapses of uveitis in Behcet's disease.
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Stanford, M. (författare)
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Whittall, T (författare)
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Bergmeier, L A (författare)
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- Lindblad, Marianne, 1941 (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för medicinsk mikrobiologi och immunologi,Institute of Medical Microbiology/Immunology
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- Lundin, Samuel B, 1970 (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för medicinsk mikrobiologi och immunologi,Institute of Medical Microbiology/Immunology
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Shinnick, T (författare)
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Mizushima, Y (författare)
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- Holmgren, Jan, 1944 (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för medicinsk mikrobiologi och immunologi,Institute of Medical Microbiology/Immunology
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Lehner, T. (författare)
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(creator_code:org_t)
- 2004-06-10
- 2004
- Engelska.
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Ingår i: Clinical and experimental immunology. - : Oxford University Press (OUP). - 0009-9104 .- 1365-2249. ; 137:1, s. 201-8
- Relaterad länk:
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https://www.ncbi.nlm...
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https://gup.ub.gu.se...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Behcet's disease (BD) specific peptide (p336-351) was identified within the human 60 kD heat shock protein (HSP60). Oral p336-351 induced uveitis in rats which was prevented by oral tolerization with the peptide linked to recombinant cholera toxin B subunit (CTB). This strategy was adopted in a phase I/II clinical trial by oral administration of p336-351-CTB, 3 times weekly, followed by gradual withdrawal of all immunosuppressive drugs used to control the disease in 8 patients with BD. The patients were monitored by clinical and ophthalmological examination, as well as extensive immunological investigations. Oral administration of p336-351-CTB had no adverse effect and withdrawal of the immunosuppressive drugs showed no relapse of uveitis in 5 of 8 patients or 5 of 6 selected patients who were free of disease activity prior to initiating the tolerization regimen. After tolerization was discontinued, 3 of 5 patients remained free of relapsing uveitis for 10-18 months after cessation of all treatment. Control of uveitis and extra-ocular manifestations of BD was associated with a lack of peptide-specific CD4+ T cell proliferation, a decrease in expression of TH1 type cells (CCR5, CXCR3), IFN-gamma and TNF-alpha production, CCR7+ T cells and costimulatory molecules (CD40 and CD28), as compared with an increase in these parameters in patients in whom uveitis had relapsed. The efficacy of oral peptide-CTB tolerization will need to be confirmed in a phase III trial, but this novel strategy in humans might be applicable generally to autoimmune diseases in which specific antigens have been identified.
Nyckelord
- Adjuvants
- Immunologic
- administration & dosage
- Administration
- Oral
- Adult
- Antigens
- CD
- immunology
- Behcet Syndrome
- complications
- immunology
- CD4-Positive T-Lymphocytes
- Cell Division
- immunology
- Cholera Toxin
- administration & dosage
- Humans
- Immune Tolerance
- Interferon Type II
- immunology
- Male
- Middle Aged
- Peptide Fragments
- Phenotype
- Receptors
- Chemokine
- immunology
- T-Lymphocytes
- immunology
- Th1 Cells
- immunology
- Tumor Necrosis Factor-alpha
- immunology
- Uveitis
- complications
- immunology
- prevention & control
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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Stanford, M.
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Whittall, T
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Bergmeier, L A
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Lindblad, Marian ...
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Lundin, Samuel B ...
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Shinnick, T
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visa fler...
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Mizushima, Y
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Holmgren, Jan, 1 ...
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Lehner, T.
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Clinical and exp ...
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Göteborgs universitet