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Oral tolerization w...
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Stanford, M.
(författare)
Oral tolerization with peptide 336-351 linked to cholera toxin B subunit in preventing relapses of uveitis in Behcet's disease.
- Artikel/kapitelEngelska2004
Förlag, utgivningsår, omfång ...
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2004-06-10
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Oxford University Press (OUP),2004
Nummerbeteckningar
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LIBRIS-ID:oai:gup.ub.gu.se/53347
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https://gup.ub.gu.se/publication/53347URI
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https://doi.org/10.1111/j.1365-2249.2004.02520.xDOI
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Ämneskategori:ref swepub-contenttype
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Ämneskategori:art swepub-publicationtype
Anmärkningar
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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.
Ämnesord och genrebeteckningar
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Adjuvants
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Immunologic
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administration & dosage
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Administration
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Oral
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Adult
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Antigens
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CD
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immunology
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Behcet Syndrome
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complications
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immunology
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CD4-Positive T-Lymphocytes
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Cell Division
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immunology
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Cholera Toxin
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administration & dosage
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Humans
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Immune Tolerance
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Interferon Type II
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immunology
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Male
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Middle Aged
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Peptide Fragments
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Phenotype
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Receptors
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Chemokine
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immunology
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T-Lymphocytes
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immunology
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Th1 Cells
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immunology
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Tumor Necrosis Factor-alpha
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immunology
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Uveitis
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complications
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immunology
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prevention & control
Biuppslag (personer, institutioner, konferenser, titlar ...)
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Whittall, T
(författare)
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Bergmeier, L A
(författare)
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Lindblad, Marianne,1941Gothenburg University,Göteborgs universitet,Institutionen för medicinsk mikrobiologi och immunologi,Institute of Medical Microbiology/Immunology(Swepub:gu)xlimar
(författare)
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Lundin, Samuel B,1970Gothenburg University,Göteborgs universitet,Institutionen för medicinsk mikrobiologi och immunologi,Institute of Medical Microbiology/Immunology(Swepub:gu)xlusam
(författare)
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Shinnick, T
(författare)
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Mizushima, Y
(författare)
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Holmgren, Jan,1944Gothenburg University,Göteborgs universitet,Institutionen för medicinsk mikrobiologi och immunologi,Institute of Medical Microbiology/Immunology(Swepub:gu)xholja
(författare)
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Lehner, T.
(författare)
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Göteborgs universitetInstitutionen för medicinsk mikrobiologi och immunologi
(creator_code:org_t)
Sammanhörande titlar
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Ingår i:Clinical and experimental immunology: Oxford University Press (OUP)137:1, s. 201-80009-91041365-2249
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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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Mizushima, Y
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Holmgren, Jan, 1 ...
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Lehner, T.
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Göteborgs universitet