Background Juvenile idiopathic arthritis (JIA) is a heterogeneous group of diseases characterized by autoimmune arthritis of unknown cause. Current treatment focuses on reduction of inflammation through anti-inflammatory and immunosuppressive strategies, including methotrexate and anti-TNF-α therapies . But, some children with JIA do not respond or are intolerant to treatment with disease-modifying antirheumatic drugs . Induction of peripheral tolerance has long been considered a promising approach to the treatment of chronic autoimmune diseases
Objectives To evaluate the therapeutic potentialities of an altered peptides ligand (APL) derived from human heat-shock protein 60 (hHsp60) for the treatment of JIA.
Methods A novel epitope of T cells located in the N terminal region of hHsp60, an autoantigen involved in the pathogenesis of autoimmune arthritis, was identified by bioinformatics tools and an APL (called APL-1) was designed starting from this epitope . We investigated the ability of this peptide for inducing regulatory T cells (Treg cells) in ex vivo assays using mononuclear cells isolated from JIA patients. In addition, we evaluated the therapeutic effect of APL-1 in collagen induced arthritis (CIA) model. Clinical score, TNFα levels and histopathology were monitored.
Results APL-1 induced a substantial increment of Treg cells in ex vivo assays using PBMC from JIA patients. The evaluation of this peptide in CIA model shows a significant reduction of arthritis score in treated mice, without present any histological damage in the joints at day 60. In addition therapy with the peptide induced a significant reduction of TNFα levels.
Conclusions The results shown here reinforce the therapeutic possibilities of APL-1 as a candidate drug for treatment of JIA. Interference of the pathogenic T cell function in a specific manner using an APL derived from an autoantigen that can induce tolerance mediated by activation of Tregs as shown here, represents an attractive therapeutic approach for autoimmune diseases.
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MC Domínguez, N. Lorenzo, A. Barbera et al (2011) An altered peptide ligand corresponding to a novel epitope from heat-shock protein 60 induces regulatory T cells and suppresses pathogenic responses in an animal model of adjuvant induced arthritis. Autoimmunity. 44:471-82.
Disclosure of Interest None declared
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