The Genetic Profile of Rheumatoid Factor-Positive Polyarticular Juvenile Idiopathic Arthritis Resembles That of Adult Rheumatoid Arthritis

• Authors: Anne Hinks, University of Manchester; Miranda C. Marion, Wake Forest University; Joanna Cobb, University of Manchester; Mary E. Comeau, Wake Forest University; Marc Sudman, Cincinnati Children's Hospital Medical Center; Hannah C. Ainsworth, Wake Forest University; John Bowes, University of Manchester; Mara L. Becker, Childrens Mercy Kansas City; John F. Bohnsack, University of Utah; Johannes‐Peter Haas, German Centre for Pediatric and Adolescent Rheumatology; Daniel J. Lovell, Cincinnati Children's Hospital Medical Center; Elizabeth D. Mellins, Stanford University; J. Lee Nelson, University of Washington; Ellen Nordal, The Arctic University of Norway; Marilynn Punaro, University of Texas; Ann M. Reed, Duke University; Carlos D. Rose, DuPont Children's Hospital; Alan M. Rosenberg, University of Saskatchewan; Marite Rygg, Norwegian University of Science and Technology; Samantha L. Smith, University of Manchester; Anne M. Stevens, University of Washington; Vibeke Videm, Norwegian University of Science and Technology; Carol A. Wallace, Seattle Childrens Hosp & Res Inst; Lucy R. Wedderburn, University College London; Annie Yarwood, University of Manchester; Rae S. M. Yeung, University of Toronto; Carl D. Langefeld, Wake Forest University; Susan D. Thompson, Cincinnati Children's Hospital Medical Center; Wendy Thomson, University of Manchester; Sampath Prahalad, Emory University
• Journal Title: Arthritis and Rheumatology
• Volume: Volume 70, Number 6
• Publisher: Wiley: 12 months | 2018-06-06, Pages 957-962
• Type of Work: Article | Final Publisher PDF
• Publisher DOI: http://doi.org/10.1002/art.40443
• Subjects: Biology, Genetics; Health Sciences, Medicine and Surgery
• Keywords: Science & Technology; Life Sciences & Biomedicine; Rheumatology; SUSCEPTIBILITY LOCI; ASSOCIATION; RISK; MHC; HLA

Abstract

Objective: Juvenile idiopathic arthritis (JIA) comprises 7 heterogeneous categories of chronic childhood arthritides. Approximately 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 those of RA and selected other JIA categories, to more fully understand the pathophysiologic relationships of inflammatory arthropathies. Methods: Patients with RF-positive polyarticular JIA (n = 340) and controls (n = 14,412) were genotyped using the Immunochip array. Single-nucleotide polymorphisms were tested for association using a logistic regression model adjusting for admixture proportions. We calculated weighted genetic risk scores (wGRS) of reported RA and JIA risk loci, and we compared the ability of these wGRS to predict RF-positive polyarticular JIA. Results: As expected, the HLA region was strongly associated with RF-positive polyarticular JIA (P = 5.51 × 10−31). Nineteen of 44 RA risk loci and 6 of 27 oligoarticular/RF-negative polyarticular JIA risk loci were associated with RF-positive polyarticular JIA (P < 0.05). The RA wGRS predicted RF-positive polyarticular JIA (area under the curve [AUC] 0.71) better than did the oligoarticular/RF-negative polyarticular JIA wGRS (AUC 0.59). The genetic profile of patients with RF-positive polyarticular JIA was more similar to that of RA patients with age at onset 16–29 years than to that of RA patients with age at onset ≥70 years. Conclusion: 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.