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  • Stanford, M. (author)

Oral tolerization with peptide 336-351 linked to cholera toxin B subunit in preventing relapses of uveitis in Behcet's disease.

  • Article/chapterEnglish2004

Publisher, publication year, extent ...

  • 2004-06-10
  • Oxford University Press (OUP),2004

Numbers

  • LIBRIS-ID:oai:gup.ub.gu.se/53347
  • https://gup.ub.gu.se/publication/53347URI
  • https://doi.org/10.1111/j.1365-2249.2004.02520.xDOI

Supplementary language notes

  • Language:English

Part of subdatabase

Classification

  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • 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.

Subject headings and genre

  • 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

Added entries (persons, corporate bodies, meetings, titles ...)

  • Whittall, T (author)
  • Bergmeier, L A (author)
  • Lindblad, Marianne,1941Gothenburg University,Göteborgs universitet,Institutionen för medicinsk mikrobiologi och immunologi,Institute of Medical Microbiology/Immunology(Swepub:gu)xlimar (author)
  • Lundin, Samuel B,1970Gothenburg University,Göteborgs universitet,Institutionen för medicinsk mikrobiologi och immunologi,Institute of Medical Microbiology/Immunology(Swepub:gu)xlusam (author)
  • Shinnick, T (author)
  • Mizushima, Y (author)
  • Holmgren, Jan,1944Gothenburg University,Göteborgs universitet,Institutionen för medicinsk mikrobiologi och immunologi,Institute of Medical Microbiology/Immunology(Swepub:gu)xholja (author)
  • Lehner, T. (author)
  • Göteborgs universitetInstitutionen för medicinsk mikrobiologi och immunologi (creator_code:org_t)

Related titles

  • In:Clinical and experimental immunology: Oxford University Press (OUP)137:1, s. 201-80009-91041365-2249

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