TY - JOUR
T1 - Autoimmune response to transthyretin in juvenile idiopathic arthritis
AU - Clement, Cristina C.
AU - Moncrieffe, Halima
AU - Lele, Aditi
AU - Janow, Ginger
AU - Becerra, Aniuska
AU - Bauli, Francesco
AU - Saad, Fawzy A.
AU - Perino, Giorgio
AU - Montagna, Cristina
AU - Cobelli, Neil
AU - Hardin, John
AU - Stern, Lawrence J.
AU - Ilowite, Norman
AU - Porcelli, Steven A.
AU - Santambrogio, Laura
N1 - Publisher Copyright:
© 2016 American Society for Clinical Investigation. All rights reserved.
PY - 2016/2/25
Y1 - 2016/2/25
N2 - Juvenile idiopathic arthritis (JIA) is the most common pediatric rheumatological condition. Although it has been proposed that JIA has an autoimmune component, the autoantigens are still unknown. Using biochemical and proteomic approaches, we identified the molecular chaperone transthyretin (TTR) as an antigenic target for B and T cell immune responses. TTR was eluted from IgG complexes and affinity purified from 3 JIA patients, and a statistically significant increase in TTR autoantibodies was observed in a group of 43 JIA patients. Three cryptic, HLA-DR1-restricted TTR peptides, which induced CD4+ T cell expansion and IFN-γ and TNF-α production in 3 out of 17 analyzed patients, were also identified. Misfolding, aggregation and oxidation of TTR, as observed in the synovial fluid of all JIA patients, enhanced its immunogenicity in HLA-DR1 transgenic mice. Our data point to TTR as an autoantigen potentially involved in the pathogenesis of JIA and to oxidation and aggregation as a mechanism facilitating TTR autoimmunity.
AB - Juvenile idiopathic arthritis (JIA) is the most common pediatric rheumatological condition. Although it has been proposed that JIA has an autoimmune component, the autoantigens are still unknown. Using biochemical and proteomic approaches, we identified the molecular chaperone transthyretin (TTR) as an antigenic target for B and T cell immune responses. TTR was eluted from IgG complexes and affinity purified from 3 JIA patients, and a statistically significant increase in TTR autoantibodies was observed in a group of 43 JIA patients. Three cryptic, HLA-DR1-restricted TTR peptides, which induced CD4+ T cell expansion and IFN-γ and TNF-α production in 3 out of 17 analyzed patients, were also identified. Misfolding, aggregation and oxidation of TTR, as observed in the synovial fluid of all JIA patients, enhanced its immunogenicity in HLA-DR1 transgenic mice. Our data point to TTR as an autoantigen potentially involved in the pathogenesis of JIA and to oxidation and aggregation as a mechanism facilitating TTR autoimmunity.
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U2 - 10.1172/jci.insight.85633
DO - 10.1172/jci.insight.85633
M3 - Article
AN - SCOPUS:85057026254
SN - 2379-3708
VL - 1
JO - JCI Insight
JF - JCI Insight
IS - 2
M1 - e85633
ER -