Proinflammatory responses to self HLA epitopes are triggered by molecular mimicry to Epstein-Barr virus proteins in oligoarticular juvenile idiopathic arthritis

Margherita Massa, Federica Mazzoli, Patrizia Pignatti, Fabrizio De Benedetti, Maristella Passalia, Stefania Viola, Rodrigo Samodal, Antonio La Cava, Francesca Giannoni, W. Ollier, Alberto Martini, Salvatore Albani

Research output: Contribution to journalArticlepeer-review

Abstract

Objective. To evaluate whether abnormal T cell recognition may be generated by exposure to exogenous antigens presenting sequence homology with epitopes contained in self HLA alleles, and if such recognition may be part of the mechanisms that fuel inflammation in autoimmune diseases associated with certain HLA alleles. Methods. Cytotoxic responses of peripheral blood mononuclear cells to 9-mer peptides derived from HLA molecules (DRB1*1101, DRB1*0801, or DPB1*0201) associated with oligoarticular juvenile idiopathic arthritis (JIA) or homologous peptides derived from Epstein-Barr virus (EBV) proteins (Bolfl or Balf2) were analyzed in patients with oligoarticular JIA and in healthy controls matched for HLA-DRB1*1101, DRB1*0801, or DPB1*0201. Production of proinflammatory cytokines in culture supernatants was determined by enzyme-linked immunosorbent assay. Results. T cell cytotoxic responses and production of proinflammatory cytokines in response to stimulation with self HLA-derived peptides were found only in patients with oligoarticular JIA, and not in controls. Patients with oligoarticular JIA, but none of the healthy controls, had EBV-self HLA cross-reactive T cells. Conclusion. Our data suggest a disease- and allele-specific mechanism of autoimmunity in oligoarticular JIA. This mechanism may be part of the pathogenesis of the disease, and could be the basis of one of the likely multiple candidates for antigen-specific immunotherapy approaches in the future.

Original languageEnglish
Pages (from-to)2721-2729
Number of pages9
JournalArthritis and Rheumatism
Volume46
Issue number10
DOIs
Publication statusPublished - Oct 1 2002

ASJC Scopus subject areas

  • Immunology
  • Rheumatology

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