Resumen

DOMINGUEZ, María del C et al. Therapeutic effect of two altered peptide ligands derived from the human heat shock protein 60 in experimental models of rheumatoid arthritis. Biotecnol Apl [online]. 2013, vol.30, n.2, pp.153-156. ISSN 1027-2852.

Induction of immune tolerance as therapeutic approach for autoimmune diseases constitutes a current research focal point. In this sense, two Altered Peptide Ligands (APLs) were evaluated for the induction of peripheral tolerance in patients with Rheumatoid Arthritis (RA). Two novel T cell epitopes from human heat-shock protein 60 (hHsp60), an autoantigen involved in the pathogenesis of RA, were identified by bioinformatics tools and two APLs were designed from these epitopes (APL-1 and APL-2). APL-1 increases the proportions of the CD4+CD25highFoxP3+ regulatory T cells in ex vivo assays using PBMCs isolated from RA patients. While, APL-2 increased the IL-10 level and suppressed IL-17 secretion, and induces the activation of T cells through his ability to modify cell cycle phase's distribution of CD4+ T cells from RA patients. Additionally, the therapeutic effect of these APLs in two animal models was evaluated: adjuvant induced arthritis (AA) in Lewis rat and collagen induced arthritis (CIA) in DBA/1 mice. Our approach was compared to metotrexate (MTX), the treatment of reference for RA, in CIA model. Clinical score, TNF-a levels and histopathology were monitored. Both APLs efficiently inhibited the course of AA and CIA, with significant reduction of the clinical and histopathology scores. The therapeutic effect induced by APLs is mediated by different molecular mechanisms, associated with immunologic tolerance. These results indicate a therapeutic potentiality of these APLs and support further investigation for treatment of RA. This study won the Annual Award of the Academy of Sciences of Cuba in 2012.

Palabras clave : rheumatoid arthritis; altered peptide ligand; hHsp60; immune tolerance; regulatory T cells; collagen induced arthritis; adjuvant induced arthritis.

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