Autoimmune response to transthyretin in juvenile idiopathic arthritis.
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ABSTRACT:
SUBMITTER: Clement CC
PROVIDER: S-EPMC4784708 | biostudies-literature | 2016 Feb
REPOSITORIES: biostudies-literature
Publications
Autoimmune response to transthyretin in juvenile idiopathic arthritis.
Clement Cristina C CC Moncrieffe Halima H Lele Aditi A Janow Ginger G Becerra Aniuska A Bauli Francesco F Saad Fawzy A FA Perino Giorgio G Montagna Cristina C Cobelli Neil N Hardin John J Stern Lawrence J LJ Ilowite Norman N Porcelli Steven A SA Santambrogio Laura L
JCI insight 20160225 2
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 ...[more]
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Project description:Juvenile idiopathic arthritis (JIAs) is the most common chronic rheumatic disease of childhood and is an important cause of disability. The folic acid analog methotrexate is the first choice disease-modifying anti-rheumatic drug in this disease, however, 35-45% of patients fail to respond. Molecular elements, such as variants in genes of pharmacological relevance, influencing response to methotrexate in JIA, would be important to individualize treatment strategies. Several studies have evaluated the effects of candidate genetic variants in the complex pathway of genes involved in methotrexate pharmacodynamics and pharmacokinetics, however, results are still contrasting and no definitive genetic marker of methotrexate response useful for the clinician to tailor therapy of children with JIA has been identified. Recently, genome-wide approaches have been applied, identifying new potential biological processes involved in methotrexate response in JIA such as TGF-beta signaling and calcium channels. If these genomic results are properly validated and integrated with innovative analyses comprising deep sequencing, epigenetics, and pharmacokinetics, they will greatly contribute to personalize therapy with methotrexate in children with JIA.
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