The genetic profile of RF-positive polyarticular juvenile idiopathic arthritis (JIA) resembles adult rheumatoid arthritis (RA).
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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.
Published Version (Please cite this version)10.1002/art.40443
Publication InfoHinks, Anne; Marion, Miranda C; Cobb, Joanna; Comeau, Mary E; Sudman, Marc; Ainsworth, Hannah C; ... Prahalad, Sampath (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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Associate Professor of Pediatrics
My long-term research goal 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. My current translational research focuses on methotrexate and its effect upon the folate pathway, utilizing cellular biomarkers and genetic differences to predict drug efficacy and minimize toxicity in JIA. My work has expanded through key collaborations, to include a mouse model for experi
Samuel L. Katz Distinguished Professor of Pediatrics
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 di
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