The genetic profile of RF-positive polyarticular juvenile idiopathic arthritis (JIA) resembles adult rheumatoid arthritis (RA).
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2018-02-09
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OBJECTIVE: Juvenile idiopathic arthritis (JIA) is comprised of seven heterogeneous categories of chronic childhood arthritides. About 5% of children with JIA have rheumatoid factor (RF) positive arthritis, which phenotypically resembles adult rheumatoid arthritis (RA). Our objective was to compare and contrast the genetics of RF-positive polyarticular JIA with RA, and selected other JIA categories, to more fully understand the pathophysiological relationships of inflammatory arthropathies. METHODS: RF-positive polyarticular JIA cases (n=340) and controls (n=14,412) were genotyped using the Immunochip array. Single nucleotide polymorphisms (SNPs) were tested for association using a logistic regression model adjusting for admixture proportions. Weighted genetic risk scores (wGRS) of published RA and JIA risk loci were calculated and their ability to predict RF-positive polyarticular JIA were compared. RESULTS: As expected, the HLA region was strongly associated with RF-positive polyarticular JIA (p=5.51x10-31). Nineteen of 44 RA risk loci and 6 of 27 oligoarticular/RF-negative polyarticular JIA risk loci were associated (p<0.05) with RF-positive polyarticular JIA. The RA wGRS predicted RF-positive polyarticular JIA (AUC=0.71) better than the oligoarticular/RF-negative polyarticular JIA wGRS (AUC=0.56). RF-positive polyarticular JIA was also genetically more similar to RA patients with age at onset <30 years compared to RA onset >70 years. CONCLUSIONS: RF-positive polyarticular JIA is genetically more similar to adult RA than to the most common JIA categories and thus appears to be a childhood-onset presentation of autoantibody positive RA. These findings suggest common disease mechanisms, which could lead to novel therapeutic targets and shared treatment strategies. This article is protected by copyright. All rights reserved.
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Hinks, Anne, Miranda C Marion, Joanna Cobb, Mary E Comeau, Marc Sudman, Hannah C Ainsworth, John Bowes, undefined Juvenile Idiopathic Arthritis Consortium for Immunochip, et al. (2018). The genetic profile of RF-positive polyarticular juvenile idiopathic arthritis (JIA) resembles adult rheumatoid arthritis (RA). Arthritis Rheumatol. 10.1002/art.40443 Retrieved from https://hdl.handle.net/10161/16095.
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Mara Becker
Dr. Becker is currently a Professor of Pediatrics and the Vice Dean for Faculty at Duke University School of Medicine. Prior to arriving at Duke in 2019, she spent 13 years at Children’s Mercy, Kansas City where she completed additional fellowship training in pediatric clinical pharmacology and served as Division Director of Rheumatology and Associate Chair for the Department of Pediatrics. At Duke, Dr. Becker served as the Vice Chair for Faculty in Pediatrics, until she assumed the role of Vice Dean for Faculty in July, 2022.
Dr. Becker’s translational research interest is to identify factors that enhance response and minimize toxicity to drugs used for the treatment of diseases in children, focusing on an individualized therapeutic strategy. Her work focuses on methotrexate and its effect upon the folate pathway, utilizing cellular biomarkers and genetic differences to predict drug efficacy in patients with JIA. Her research has been funded by the Kansas City Area Life Sciences Institute, the PhRMA Foundation, the Rheumatology Research Foundation, and the National Institutes of Health. She has also served as a faculty leader at the Duke Clinical Research Institute where her work expanded to developing and supporting novel networks to carry out research and clinical trials, focusing on children with rare rheumatic and genetic conditions including the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry.
In her new role as Vice Dean, she has focused on fortifying and reimagining the Office for Faculty and the multiple programs and offices that support faculty in the School of Medicine. New efforts in this role will focus on identifying opportunities to create standardized and transparent processes within the office, prioritizing leadership development for current leaders in the School of Medicine, and developing a training and mentorship program in Restorative Justice to strengthen community and support a healthy and productive work climate. In addition to her administrative work at Duke, Dr. Becker has held multiple leadership roles in national committees and organizations in her field.
Ann Marie Reed
I have spent my career caring for children with autoimmune disorders and immune dysfunction. I have focused my work caring for children with juvenile dermatomyositis and auto inflammatory disorders. I have overseen a research program for 24 years studying the genetics and cause of human autoimmune disease, focused on dermatomyositis in children and adults. The long-term goal of my research team is to develop new biomarkers of diseases to identify those predisposed to develop disease, as well as monitor disease activity and response to treatment. My team makes extensive use of genomics, gene expression, protein expression and immunohistochemical techniques to study the inflammatory and non-inflammatory aspects of dermatomyositis diseases. Other autoimmune disease processes, including systemic lupus and vasculitis, have been focused on as well.
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