The genetic profile of RF-positive polyarticular juvenile idiopathic arthritis (JIA) resembles adult rheumatoid arthritis (RA).

Research output: Contribution to journalArticle

  • External authors:
  • Anne Hinks
  • Miranda C. Marion
  • Joanna Cobb
  • Mary E. Comeau
  • Marc Sudman
  • Hannah C Ainsworth
  • Mara L Becker
  • John F. Bohnsack
  • Johannes-Peter Haas
  • Daniel J Lovell
  • Elizabeth D Mellins
  • J. Lee Nelson
  • Ellen Nordal
  • Marilynn Punaro
  • Ann M. Reed
  • Carlos D. Rosé
  • Alan M Rosenberg
  • Marite Rygg
  • Samantha L Smith
  • Anne M Stevens
  • Vibeke Videm
  • Carol A. Wallace
  • Lucy R Wedderburn
  • Rae S M Yeung
  • Carl D. Langefeld
  • Susan D. Thompson
  • Sampath Prahalad

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.

Bibliographical metadata

Original languageEnglish
Pages (from-to)957-962
JournalArthritis and Rheumatology
Volume70
Issue number6
Early online date9 Feb 2018
DOIs
Publication statusPublished - 2018

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