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.

Figure 1

Comparison of the weighted genetic risk score (wGRS) generated using loci associated with the highest risk of rheumatoid arthritis (RA) with the wGRS generated using loci associated with the highest risk of oligoarticular/rheumatoid factor (RF)–negative polyarticular juvenile idiopathic arthritis (JIA) for the purpose of predicting cases of RF‐positive polyarticular JIA (RFposPolys). AUC = area under the curve.

Figure 2

A, Comparison of the ability of the wGRS generated using loci associated with the highest risk of RA to predict cases of RF‐positive polyarticular JIA with the ability of the same wGRS to predict cases of early‐onset RA (ages 16–29 years). B, Comparison of the ability of the wGRS generated using loci associated with the highest risk of RA to predict cases of RF‐positive polyarticular JIA with the ability of the same wGRS to predict cases of later‐onset RA (age ≥70 years). See Figure 1 for definitions.