The genetic profile of RF-positive polyarticular juvenile idiopathic arthritis (JIA) resembles adult rheumatoid arthritis (RA).
Abstract
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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https://hdl.handle.net/10161/16095Published Version (Please cite this version)
10.1002/art.40443Publication Info
Hinks, 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.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
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Show full item recordScholars@Duke
Mara Becker
Professor of Pediatrics
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 rol
Ann Marie Reed
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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