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


CONCLUSIONS
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.
Massa
Margherita
M
IRCCS Policlinico San Matteo, Pavia, Italy.
Mazzoli
Federica
F
Pignatti
Patrizia
P
De Benedetti
Fabrizio
F
Passalia
Maristella
M
Viola
Stefania
S
Samodal
Rodrigo
R
La Cava
Antonio
A
Giannoni
Francesca
F
Ollier
W
W
Martini
Alberto
A
Albani
Salvatore
S
D000293:Adolescent; D000328:Adult; D001171:Arthritis, Juvenile / Q000276:immunology* / Q000821:virology; D002648:Child; D002675:Child, Preschool; D003429:Cross Reactions / Q000276:immunology; D004268:DNA-Binding Proteins / Q000276:immunology; D000939:Epitopes / Q000276:immunology*; D006684:HLA-DR Antigens / Q000276:immunology*; D059811:HLA-DRB1 Chains; D004854:Herpesvirus 4, Human / Q000276:immunology*; D006801:Humans; D018716:Molecular Mimicry / Q000276:immunology*; D018995:Myosin Heavy Chains / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014764:Viral Proteins / Q000276:immunology
C096364:BALF2 protein, Human herpesvirus 4; C069498:BOLF1 protein, Human herpesvirus 4; D004268:DNA-Binding Proteins; D000939:Epitopes; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; C466440:HLA-DRB1*08:01 antigen; D014764:Viral Proteins; D018995:Myosin Heavy Chains