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Clin Exp Med ; 15(1): 31-9, 2015 Feb.
Article in English | MEDLINE | ID: mdl-24474501

ABSTRACT

Juvenile idiopathic arthritis (JIA) is a heterogeneous group of diseases characterized by autoimmune arthritis of unknown cause with onset before age of 16 years. Methotrexate provides clinical benefits in JIA. For children who do not respond to methotrexate, treatment with anti-tumor necrosis factor (TNF)-α is an option. However, some patients do not respond or are intolerant to anti-TNF therapy. Induction of peripheral tolerance has long been considered a promising approach to the treatment of chronic autoimmune diseases. We aimed to evaluate the potentialities of two altered peptide ligands (APLs) derived from human heat-shock protein 60, an autoantigen involved in the pathogenesis of autoimmune arthritis, in JIA patients. Interferon (IFN)-γ, TNF-α and interleukin (IL)-10 levels were determined in ex vivo assays using peripheral blood mononuclear cells (PBMC) from these patients. Wild-type peptide and one of these APLs increased IFN-γ and TNF-α levels. Unlike, the other APLs (called APL2) increased the IL-10 level without affecting IFN-γ and TNF-α levels. On the other hand, APL2 induces a marked activation of T cells since it transforms cell cycle phase's distribution of CD4+ T cells from these patients. In addition, we evaluated the therapeutic effect of APL2 in collagen-induced arthritis model. Therapy with APL2 reduced arthritis scores and histological lesions in mice. This effect was associated to a decrease in TNF-α and IL-17 levels. These results indicate a therapeutic potentiality of APL2 for JIA.


Subject(s)
Arthritis, Experimental/drug therapy , Arthritis, Juvenile/immunology , Autoantigens/pharmacology , Chaperonin 60/chemistry , Leukocytes, Mononuclear/drug effects , Mitochondrial Proteins/chemistry , Peptides/pharmacology , Adolescent , Animals , Antirheumatic Agents/pharmacology , Arthritis, Experimental/genetics , Arthritis, Experimental/immunology , Arthritis, Experimental/pathology , Arthritis, Juvenile/genetics , Arthritis, Juvenile/pathology , Autoantigens/chemistry , Chaperonin 60/genetics , Chaperonin 60/immunology , Child , Child, Preschool , Gene Expression Regulation , Humans , Interferon-gamma/biosynthesis , Interferon-gamma/metabolism , Interleukin-10/biosynthesis , Interleukin-10/metabolism , Interleukin-17/antagonists & inhibitors , Interleukin-17/biosynthesis , Interleukin-17/metabolism , Leukocytes, Mononuclear/immunology , Leukocytes, Mononuclear/pathology , Methotrexate/pharmacology , Mice , Mitochondrial Proteins/genetics , Mitochondrial Proteins/immunology , Peptides/chemical synthesis , Peripheral Tolerance , Primary Cell Culture , Signal Transduction , Sulfasalazine/pharmacology , Tumor Necrosis Factor-alpha/antagonists & inhibitors , Tumor Necrosis Factor-alpha/biosynthesis , Tumor Necrosis Factor-alpha/metabolism
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