Epitopes described in "Tolerogenic immune responses to novel T-cell epitopes from heat-shock protein 60 in juvenile idiopathic arthritis."

Article Authors:Sylvia Kamphuis; Wietse Kuis; Wilco de Jager; Gijs Teklenburg; Margherita Massa; Grace Gordon; Marjolein Boerhof; Ger T Rijkers; Cuno S Uiterwaal; Henny G Otten; Alessandro Sette; Salvatore Albani; Berent J Prakken
Article Title:Tolerogenic immune responses to novel T-cell epitopes from heat-shock protein 60 in juvenile idiopathic arthritis.
Reference Detail
Reference ID:1014625
Abstract:BACKGROUND: Juvenile idiopathic arthritis is a heterogeneous autoimmune disease characterised by chronic inflammation of one or more joints. In patients with this disease, T-cell reactivity to autologous heat-shock protein 60 (HSP60) is associated with a favourable prognosis. We sought to identify HSP60 T-cell epitopes to find potential targets for HSP60 immunotherapy and to assess whether immune responses to these epitopes contribute to the distinct clinical outcome of this disease. METHODS: We identified eight potential epitopes using a computer algorithm from both self and microbial HSP60 binding to many HLA-DR molecules. We analysed the pattern of T-cell responses induced by these HSP60 peptides in peripheral-blood mononuclear cells (PBMC) of 57 patients with juvenile idiopathic arthritis, 27 healthy controls, and 20 disease controls. We undertook in-vitro MHC binding studies with the identified peptides, and HLA class II typing of a subset of patients with juvenile idiopathic arthritis. FINDINGS: Five of the eight peptides identified yielded proliferative T-cell responses in 50-70% of PBMC from patients with juvenile idiopathic arthritis irrespective of MHC genotype, but not in PBMC from healthy or disease controls. Although PBMC from both patients with juvenile idiopathic arthritis and healthy controls produced interferon gamma in response to these peptides, only PBMC from patients with the disease produced interleukin 10. INTERPRETATION: The recorded T-cell-induction in juvenile idiopathic arthritis is tolerogenic. In patients with oligoarticular disease, the immune responses to the HSP60 epitopes identified could contribute to disease remission. RELEVANCE TO PRACTICE: The broad recognition of these HSP60 epitopes in a population of patients with polymorphic MHC genotypes opens the way for HSP60-peptide immunotherapy, representing a novel treatment option to specifically modulate the immune system in patients with juvenile idiopathic arthritis.
Reference Type:Literature
PubMed ID:15993233
Journal Volume:366
Article Pages:50-6
Journal ISSN:1474-547X
Article Chemical List:Chaperonin 60;Cytokines;Epitopes, T-Lymphocyte
Article MeSH List:Adolescent; Arthritis, Juvenile(genetics; immunology; therapy); Chaperonin 60(immunology); Child; Child, Preschool; Cytokines(metabolism); Epitopes, T-Lymphocyte(immunology); Female; Humans; Immune Tolerance; Immunotherapy, Active; Lymphocyte Activation; Major Histocompatibility Complex; Male; Prognosis; T-Lymphocytes(immunology)
Curation Last Updated:2015-01-27 20:37:30