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 [1]. But, some children with JIA do not respond or are intolerant to treatment with disease-modifying antirheumatic drugs [2]. 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 [3]. 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.

References

1. Prakken B, Albani Se, Martini A (2011) Juvenile idiopathic arthritis. Lancet. 377:2138–49.

2. Horneff G, Schmeling H, Biedermann T et al (2004) The German etanercept registry for treatment of juvenile idiopathic arthritis. Ann. Rheum. Dis. 63:1638–44.

3. 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

DOI 10.1136/annrheumdis-2014-eular.1908