Clinical and Experimental Medicine

, Volume 15, Issue 1, pp 31–39

APL-2, an altered peptide ligand derived from heat-shock protein 60, induces interleukin-10 in peripheral blood mononuclear cell derived from juvenile idiopathic arthritis patients and downregulates the inflammatory response in collagen-induced arthritis model

  • Norailys Lorenzo
  • Dolores Cantera
  • Ariana Barberá
  • Amaris Alonso
  • Elsy Chall
  • Lourdes Franco
  • Julio Ancizar
  • Yanetsy Nuñez
  • Fiorella Altruda
  • Lorenzo Silengo
  • Gabriel Padrón
  • Maria del Carmen Dominguez
Original Article

DOI: 10.1007/s10238-014-0273-x

Cite this article as:
Lorenzo, N., Cantera, D., Barberá, A. et al. Clin Exp Med (2015) 15: 31. doi:10.1007/s10238-014-0273-x

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.

Keywords

Altered peptide ligand Juvenile idiopathic arthritis Collagen-induced arthritis Tolerance Interleukin-10 

Copyright information

© Springer-Verlag Italia 2014

Authors and Affiliations

  • Norailys Lorenzo
    • 1
  • Dolores Cantera
    • 2
  • Ariana Barberá
    • 1
  • Amaris Alonso
    • 3
  • Elsy Chall
    • 4
  • Lourdes Franco
    • 4
  • Julio Ancizar
    • 1
  • Yanetsy Nuñez
    • 3
  • Fiorella Altruda
    • 5
  • Lorenzo Silengo
    • 5
  • Gabriel Padrón
    • 1
  • Maria del Carmen Dominguez
    • 1
  1. 1.Biomedical Research DepartmentCenter for Genetic Engineering and BiotechnologyHavanaCuba
  2. 2.Pedro Borras HospitalHavanaCuba
  3. 3.William Soler HospitalHavanaCuba
  4. 4.Hospital of Centro HabanaHavanaCuba
  5. 5.Department of Molecular Biotechnology and Health SciencesMolecular Biotechnology CenterTurinItaly