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

• Published in: Arthritis & rheumatology (Hoboken, N.J.) N.J.), 2018-06, Vol.70 (6), p.957-962
• Main Authors: Hinks, Anne, Marion, Miranda C., Cobb, Joanna, Comeau, Mary E., Sudman, Marc, Ainsworth, Hannah C., Bowes, John, Becker, Mara L., Bohnsack, John F., Haas, Johannes‐Peter, Lovell, Daniel J., Mellins, Elizabeth D., Nelson, J. Lee, Nordal, Ellen, Punaro, Marilynn, Reed, Ann M., Rose, Carlos D., Rosenberg, Alan M., Rygg, Marite, Smith, Samantha L., Stevens, Anne M., Videm, Vibeke, Wallace, Carol A., Wedderburn, Lucy R., Yarwood, Annie, Yeung, Rae S. M., Langefeld, Carl D., Thompson, Susan D., Thomson, Wendy, Prahalad, Sampath
• Format: Article
• Language: English
• Subjects: Admixtures; Adolescent; Adult; Arthritis; Arthritis, Juvenile - genetics; Arthritis, Juvenile - immunology; Arthritis, Rheumatoid - genetics; Arthritis, Rheumatoid - immunology; Autoantibodies; Autoantibodies - genetics; Brief Report; Categories; Child; Children; Clinical medical disciplines: 750; Female; Genetic Profile; Genetics; Genotype; Histocompatibility antigen HLA; Humans; Inflammation; Klinisk medisinske fag: 750; Loci; Logistic Models; Male; Medical disciplines: 700; Medisinske Fag: 700; Patients; Pediatric Rheumatology; Phenotype; Phenotypes; Polymorphism, Single Nucleotide; Regression models; Reumatologi: 759; Rheumatoid arthritis; Rheumatoid factor; Rheumatoid Factor - genetics; Rheumatoid Factor - immunology; Rheumatology: 759; Risk; Therapeutic applications; VDP
• ISSN: 2326-5191; 2326-5205; 2326-5205
• DOI: 10.1002/art.40443

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.