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

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 EpsteinBarr virus (EBV) proteins (Bolf1 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 enzymelinked 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.

Allele-dependent Similarity between Viral and Self-peptide Presentation by HLA-B27 Subtypes

“…4 and this study). On the other hand, although the presence of EBV-specific and self-cross-reactive CTL has been demonstrated in the periphery and joints, for example in patients with oligoarticular juvenile idiopathic arthritis (49), an epidemiological association between AS and EBV has not been found so far and is hard to demonstrate given the fact that about 90% of humans get this infection during the first decades of life (35). Furthermore, no animal models are available involving presentation of pVIPR and pLMP2 in the context of HLA-B27.…”

Antibiotic Exposure and Juvenile Idiopathic Arthritis: A Case–Control Study

“…1 Despite the presence of known genetic risk factors, population-based studies suggest that genetics explains only 10% to 25% of disease incidence. 2,3 Environmental triggers such as viral infections have been suggested, [4][5][6] but other studies have not substantiated these findings. [7][8][9][10] One study found that hospitalization for infection in the first year of life was associated with an increased risk of developing JIA.…”

New advances in juvenile idiopathic arthritis

“…Patients with JIA have been reported to have higher rates of infection with mycoplasma pneumonia, (20) streptococcus, (21) parvovirus B19, (22) and Epstein-Barr virus than children who do not have JIA. (23) However, the mechanism through which infection increases the risk of JIA and other autoimmune diseases remains unclear. Molecular mimicry, whereby self-reactivity is triggered by cross-recognition of a self-peptide and an infectious peptide because of sequence similarity, has been reported.…”