J Pharm Pharmacogn Res 2(Suppl. 1): S41, 2014
Special supplement with the abstract book of LATINFARMA 2013
CO 066: CIGB-814, A PEPTIDE AS IMMUNOMODULATOR FOR THE TREATMENT OF RHEUMATOID ARTHRITIS
Domínguez MC1, Lorenzo N1, Barberá A1, Ancizar JA1, Torres AM2, Hernandez MV2, Hernandez I2, Gil R2, Altruda F3, Silengo L3, Padrón GR1.
Induction of immune tolerance as therapeutic approach for autoimmune diseases constitutes a current research focal point. In this sense, we aimed to evaluate an Altered Peptides Ligand (APL) for induction of peripheral tolerance in patients with Rheumatoid Arthritis (RA). A novel T cell epitope from human heat-shock protein 60 (Hsp60), an autoantigen involved in the pathogenesis of RA, was identified by bioinformatics tools and an APL was design from this epitope (CIGB-814). Firstly, we investigated the ability of this peptide for inducing regulatory T cells (Treg cells) in mice. CIGB-814 induced an increase of the proportions of Treg cells in the draining lymph nodes of the injected site in mice. On other hand, this peptide increases the proportions of the CD4+CD25highFoxP3+ Treg cells in ex vivo assays using PBMC isolated from RA patients. In addition, we evaluated the therapeutic effect of this APL in two animal models: adjuvant induced arthritis (AA) in Lewis rat and collagen induced arthritis (CIA) in DBA/1 mice. Our approach was compared to metotrexate (MTX), the gold standard treatment for RA, in CIA model. Clinical score, Treg, TNFα levels and histopathology were monitored. CIGB-814 efficiently inhibited the course of AA and CIA, with significant reduction of the clinical and histopathology score. The therapeutic effect induced by CIGB-814 is mediated by an increase of the proportions of Treg cells and a decrease of TNFα levels. These results indicate a therapeutic potentiality of this peptide and support further investigation of this candidate drugs for treatment of RA. 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 shows here, represents an attractive therapeutic approach for autoimmune diseases.
Citation Format: Domínguez MC, Lorenzo N, Barberá A, Ancizar JA, Torres AM, Hernandez MV, Hernandez I, Gil R, Altruda F, Silengo L, Padrón GR (2014) EARLY PHASE OF SYSTEMIC REACTION TO ORAL ASPIRIN CHALLENGE IS RELATED TO AN INCREASE IN THE LEVELS OF IL-6 AND THE PERCENTAGE OF EFFECTORS MEMORY T-CELLS. [abstract]. In: Proceedings of the LATINFARMA 2013; 2013 October 21–25; La Habana, Cuba: SCF; J Pharm Pharmacogn Res 2(Suppl. 1): S41.
© 2014 Journal of Pharmacy & Pharmacognosy Research (JPPRes)