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

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.

• Authors: 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
• Journal: Arthritis & rheumatology (Hoboken, N.J.) (Arthritis Rheumatol) Vol. 70 Issue 6 Pg. 957-962 (06 2018) ISSN: 2326-5205 [Electronic] United States
• PMID: 29426059 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © 2018 The Authors. Arthritis & Rheumatology published by Wiley Periodicals, Inc. on behalf of American College of Rheumatology.

Chemical References

• Autoantibodies
• Rheumatoid Factor

Topics

• Adolescent
• Adult
• Arthritis, Juvenile (genetics, immunology)
• Arthritis, Rheumatoid (genetics, immunology)
• Autoantibodies (genetics)
• Child
• Female
• Genetic Profile
• Genotype
• Humans
• Logistic Models
• Male
• Phenotype
• Polymorphism, Single Nucleotide
• Rheumatoid Factor (genetics, immunology)