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APL-1, an altered peptide ligand derived from heat-shock protein, alone or combined with methotrexate attenuates murine collagen-induced arthritis

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Abstract

Induction of tolerance to autoantigens in vivo is a complex process that involves several mechanisms such as the induction of regulatory T cells and changes in the cytokine and chemokine profiles. This approach represents an attractive alternative for treatment of autoimmune diseases. APL-1 is an altered peptide ligand derived from a novel CD4 + T cell epitope of human heat-shock protein of 60 kDa (HSP60), an autoantigen involved in the pathogenesis of rheumatoid arthritis (RA). We have shown previously that this peptide efficiently inhibited the course of adjuvant-induced arthritis in Lewis rats and induced regulatory T cell (Treg) in ex vivo assay with PBMC isolated from RA patients. This study was undertaken to evaluate the therapeutic effect of APL-1 and its combination with methotrexate (MTX) in collagen-induced arthritis (CIA). CIA was induced in male DBA/1 mice at 8 weeks of age by immunization with chicken collagen. APL, MTX or both were administrated beginning from arthritis onset. Therapeutic effect was evaluated by arthritis and joint pathologic scores. In addition, TNFα and IL-10 in sera were measured by ELISA. Treg induction was assessed by FACS analysis. APL-1 inhibits efficiently the course of arthritis in CIA, similar to MTX. In addition, therapy with APL-1 plus MTX reduced CIA in mice, associated with an increase in Treg. These facts reinforce the therapeutic possibilities of APL-1 as a candidate drug for treatment of RA.

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Authors and Affiliations

  1. Biomedical Research Department, Center for Genetic Engineering and Biotechnology, P.O. Box 6162, 10600, Havana, Cuba

    Norailys Lorenzo & Maria del Carmen Dominguez

  2. Department of Genetics, Biology and Biochemistry, Molecular Biotechnology Center, Turin, Italy

    Fiorella Altruda & Lorenzo Silengo

Authors
  1. Norailys Lorenzo
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  2. Fiorella Altruda
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  3. Lorenzo Silengo
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  4. Maria del Carmen Dominguez
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Correspondence to Maria del Carmen Dominguez.

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Lorenzo, N., Altruda, F., Silengo, L. et al. APL-1, an altered peptide ligand derived from heat-shock protein, alone or combined with methotrexate attenuates murine collagen-induced arthritis. Clin Exp Med 17, 209–216 (2017). https://doi.org/10.1007/s10238-016-0412-7

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  • DOI: https://doi.org/10.1007/s10238-016-0412-7

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