Brief Report: The Genetic Profile of Rheumatoid Factor–Positive Polyarticular Juvenile Idiopathic Arthritis Resembles That of Adult Rheumatoid Arthritis

Anne Hinks, Miranda C. Marion, Joanna Cobb, Mary E. Comeau, Marc Sudman, Hannah C. Ainsworth, John Bowes, Juvenile Idiopathic Arthritis Consortium for Immunochip, 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. Rose, Alan M. Rosenberg, Marite Rygg, Samantha L. Smith, Anne M. Stevens, Vibeke Videm, Carol A. Wallace, Lucy R. Wedderburn, Annie Yarwood, Rae S. M. Yeung, Carl D. Langefeld, Susan D. Thompson, Wendy Thomson, Sampath Prahalad

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. 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. 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. 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.