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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
1
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pubmed:dateCreated |
2004-6-15
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pubmed:abstractText |
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.
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/15196263-10450513,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15196263-10528040,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15196263-10605020,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15196263-10743813,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15196263-10816874,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15196263-11007763,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15196263-1180305,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15196263-12118893,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15196263-12594851,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15196263-12813024,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15196263-1970380,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15196263-2004821,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15196263-2137841,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15196263-2503672,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15196263-2664172,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15196263-2925239,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15196263-500134,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15196263-606446,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15196263-6181359,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15196263-7519530,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15196263-7526379,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15196263-7688396,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15196263-7835927,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15196263-7929845,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15196263-8622334,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15196263-9152063,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15196263-9158087,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15196263-9176706,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15196263-9238837,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15196263-9243768,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15196263-9710222
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
0009-9104
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
137
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
201-8
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pubmed:dateRevised |
2009-11-18
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pubmed:meshHeading |
pubmed-meshheading:15196263-Adjuvants, Immunologic,
pubmed-meshheading:15196263-Administration, Oral,
pubmed-meshheading:15196263-Adult,
pubmed-meshheading:15196263-Antigens, CD,
pubmed-meshheading:15196263-Behcet Syndrome,
pubmed-meshheading:15196263-CD4-Positive T-Lymphocytes,
pubmed-meshheading:15196263-Cell Division,
pubmed-meshheading:15196263-Cholera Toxin,
pubmed-meshheading:15196263-Humans,
pubmed-meshheading:15196263-Immune Tolerance,
pubmed-meshheading:15196263-Interferon-gamma,
pubmed-meshheading:15196263-Male,
pubmed-meshheading:15196263-Middle Aged,
pubmed-meshheading:15196263-Peptide Fragments,
pubmed-meshheading:15196263-Phenotype,
pubmed-meshheading:15196263-Receptors, Chemokine,
pubmed-meshheading:15196263-T-Lymphocytes,
pubmed-meshheading:15196263-Th1 Cells,
pubmed-meshheading:15196263-Tumor Necrosis Factor-alpha,
pubmed-meshheading:15196263-Uveitis
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pubmed:year |
2004
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pubmed:articleTitle |
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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pubmed:affiliation |
Department of Ophthalmology, Guy's, King's and St. Thomas' School of Medicine and Dentistry, Guy's Hospital, London, UK.
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pubmed:publicationType |
Journal Article,
Clinical Trial,
Randomized Controlled Trial,
Research Support, Non-U.S. Gov't
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