|Göteborgs universitets publikationer
Oral tolerization with peptide 336-351 linked to cholera toxin B subunit in preventing relapses of uveitis in Behcet's disease.
Författare och institution:
M. Stanford (-); T Whittall (-); L A Bergmeier (-); Marianne Lindblad (Institutionen för medicinsk mikrobiologi och immunologi); Samuel B Lundin (Institutionen för medicinsk mikrobiologi och immunologi); T Shinnick (-); Y Mizushima (-); Jan Holmgren (Institutionen för medicinsk mikrobiologi och immunologi); T. Lehner (-)
Clinical and experimental immunology, 137 ( 1 ) s. 201-8
Artikel, refereegranskad vetenskaplig
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.
Ämne (baseras på Högskoleverkets indelning av forskningsämnen):
MEDICIN OCH HÄLSOVETENSKAP
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