Kamphuis S et al. (2005) Tolerogenic immune responses to novel T-cell epitopes from heat-shock protein 60 in juvenile idiopathic arthritis. Lancet 366: 50–56

T-cell reactivity to autologous HEAT-SHOCK PROTEIN 60 (HSP60) in juvenile idiopathic arthritis (JIA) is often associated with positive patient outcome. Specific HSP60 TOLEROGENIC EPITOPES need to be identified in order for further research into HSP60-peptide immunotherapy in autoimmune diseases to be possible.

In their recent study, Kamphuis and colleagues analyzed 8 potential HSP60 epitopes in patients with JIA. The epitopes, which were obtained using a computer algorithm, originated from both self and microbial HSP60 binding to different HLA-DR molecules. T-cell responses to each of these potential tolerogenic epitopes were analyzed in a total of 57 patients with JIA, 27 healthy controls and 20 disease control patients with diabetes.

Out of the 8 potential HSP60 epitopes, 5 peptides resulted in tolerogenic T-cell immune responses in patients with JIA (50–70%). Tolerogenic responses were not seen in either of the control patient groups. Further investigation into peptide-specific cytokine production showed that peripheral-blood mononuclear cells from both the patients with JIA and the healthy controls produced interferon-γ when reacting to the peptides in question. Antigen-specific production of interleukin-10, however, was only induced in cells from patients with JIA.

The authors conclude that the set of pan-DR peptides identified can provide better insight into the inflammation control mechanism observed in oligoarticular JIA. Further studies should investigate if the newly identified epitopes are involved in other HSP60-related inflammatory diseases, such as rheumatoid arthritis and atherosclerosis.