Genetic Data Can Improve Clinical Understanding of Juvenile Idiopathic Arthritis

Personalized Medicine and Genetic Testing to Predict Treatment Response
Personalized Medicine and Genetic Testing to Predict Treatment Response
The study assessed the implications of genetic advances in juvenile idiopathic arthritis; the results of the research may be useful in the treatment of arthritis in children.

Current nomenclature does not accurately reflect the continuity between juvenile idiopathic arthritis (JIA) and adult arthritis, according to research published in Current Opinion in Rheumatology. However, results of the research showed that genetic data can indicate an association between JIA and adult arthritis.

In the review, researchers outlined recent findings in the genetics of JIA, the implications, and how these advances can inform the evolving clinical understanding of inflammatory arthritis in children.

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The International Leagues of Associations for Rheumatology (ILAR) developed 7 categories to classify JIA in patients; however, several challenges exist within these classifications, including “intricate and often counterintuitive” inclusion and exclusion criteria, category-switching in patients followed over time, and evidence that ILAR boundaries do not currently reflect underlying disease biology.

According to the researchers, it is now more important than ever to correctly categorize patient populations with JIA to maximize opportunities associated with mechanism-directed therapy. Recent categorization attempts have used clinical and blood-based biomarkers, joint trajectories, and informed expert opinions, but these efforts have been limited. Researchers also noted that patient phenotyping remains important, particularly when used in conjunction with complementary clinical approaches.

Genetics is one such approach that could be useful in understanding polygenic diseases like JIA. Genome-wide association studies can identify risk modulation from common gene variants, but the interpretation of data results can be challenging. Numerous approaches are currently being examined to address the challenges inherent in genetic subtyping. For example, researchers designed the Immunochip to focus genetic studies on 186 loci of immunologic interest to better localize causal variants.

In addition, investigators noted several well-documented associations between JIA and the human leukocyte antigen (HLA) in the last 40 years. They indicated that the age of onset, not the oligoarticular or polyarticular presentation, is the main driver of HLA association. Such associations typically indicate strong evidence for the involvement of antigen-specific T cells in the pathogenesis of the disease.

Researchers suggest that despite challenges, it is important for clinicians to note the significance of the identified loci for the pathogenesis of JIA.

“Technical and bioinformatic advances have yielded important new insights into the genetics of JIA,” the researchers noted. “At a most basic level, studies of both HLA and non-HLA associations show that the ‘hard stop’ between JIA and adult arthritis at age 16 fails to correspond to a biologic dividing line. Rather, inflammatory arthritis is likely to represent a continuum across the age spectrum.”

The investigators concluded by calling for future studies to examine the loci implicated in both JIA and adult arthritis, which would provide continued insight into disease pathogenesis.


Nigrovic PA, Martinez-Bonet M, Thompson SD. Implications of juvenile idiopathic arthritis genetic risk variants for disease pathogenesis and classification. Curr Opin Rheumatol. 2019;31(5):401-410.