Rheumatology International

, Volume 32, Issue 6, pp 1819–1825

Weak CD4+ T-cell responses to citrullinated vimentin in rheumatoid arthritis patients carrying HLA-DR9 alleles

  • Diego Catalán
  • Octavio Aravena
  • Roberto Zúñiga
  • Natalia Silva
  • Alejandro Escobar
  • Francisca Sabugo
  • Pamela Wurmann
  • Lilian Soto
  • Rodrigo González
  • Jorge Alfaro
  • Milton Larrondo
  • Miguel Cuchacovich
  • Juan Carlos Aguillón
Short Communication

DOI: 10.1007/s00296-011-2039-z

Cite this article as:
Catalán, D., Aravena, O., Zúñiga, R. et al. Rheumatol Int (2012) 32: 1819. doi:10.1007/s00296-011-2039-z

Abstract

Citrullinated vimentin (cVIM) is one of the antigens specifically targeted by anti-citrullinated protein antibodies (ACPA) in rheumatoid arthritis (RA) patients. The association between ACPA and certain HLA-DRB1 alleles, those coding for the shared epitope (SE), suggests that this response could be T-cell mediated. HLA-DR9 alleles, which do not code for the SE, have recently been associated with ACPA (+) RA. The objective of this work was to study CD4+ T cell responses to cVIM in RA patients and healthy controls carrying HLA-DR9 alleles. Fourteen RA patients and ten healthy controls previously genotyped for HLA-DRB1 were studied for the presence of serum anti-cVIM antibodies by Western blot and ELISA. Peripheral blood mononuclear cells were stimulated with native vimentin and cVIM, and CD4+ T cells proliferation was assessed by flow cytometry. Citrulline-specific CD4+ T cells proliferation was found not only in RA patients but also in healthy controls. Although most patients carrying HLA-DR9 alleles present anti-cVIM antibodies, HLA-DR9 alleles were associated with weaker cVIM-driven CD4+ T-cell responses among RA patients. These results suggest that HLA-DR9 alleles could exert a protective effect on the recognition of cVIM epitopes by CD4+ T cells. In this context, other citrullinated proteins may break T and B cell tolerance, with cVIM only acting as a cross-reactive target for ACPA.

Keywords

Rheumatoid arthritis Vimentin Anti-citrullinated protein antibodies Autoantigens CD4+ T cells HLA-DRB1 

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Diego Catalán
    • 1
    • 2
  • Octavio Aravena
    • 1
  • Roberto Zúñiga
    • 1
  • Natalia Silva
    • 1
  • Alejandro Escobar
    • 1
  • Francisca Sabugo
    • 3
  • Pamela Wurmann
    • 3
  • Lilian Soto
    • 3
  • Rodrigo González
    • 3
  • Jorge Alfaro
    • 3
  • Milton Larrondo
    • 3
  • Miguel Cuchacovich
    • 3
  • Juan Carlos Aguillón
    • 1
    • 2
  1. 1.Programa Disciplinario de Inmunología, Instituto de Ciencias Biomédicas (ICBM), Facultad de MedicinaUniversidad de ChileIndependenciaChile
  2. 2.Millennium Institute on Immunology and Immunotherapy P09-016-FIndependenciaChile
  3. 3.Hospital ClínicoUniversidad de ChileIndependenciaChile

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