Genetic Differences by Type of Juvenile Idiopathic Arthritis

Genetic risk factors for systemic juvenile idiopathic arthritis are uniquely different from other types of juvenile idiopathic arthritis, shows a study published in the Annals of the Rheumatic Diseases.

In this study, published in December, researchers found no shared heritable risk factors between systemic juvenile idiopathic arthritis and juvenile idiopathic arthritis. They did, however, find two novel susceptibly loci that met genome-wide significance for association with systemic juvenile idiopathic arthritis. These findings may inform reclassifications of juvenile idiopathic arthritis as well as new therapies for treating systemic juvenile idiopathic arthritis.

Systemic juvenile idiopathic arthritis is a rare form of juvenile idiopathic arthritis characterized by systemic inflammation, rash and fever. Macrophage activation system can also occur as a result of systemic juvenile idiopathic arthritis. To date, no single therapy is universally effective in treating systemic juvenile idiopathic arthritis and great variability exists with regard to therapy response. Current treatment options include methotrexate and glucorticoids. Given the unique clinical features of systemic juvenile idiopathic arthritis, some argue that it should be classified as an autoinflammatory disease and distinguished from other forms of child-onset arthritis.

“These distinct genetic data provide hard evidence that these conditions differ in pathophysiology, strongly supporting the clinical distinction between sJIA and the other JIA subtypes. Considering the ongoing discussions about restructuring the JIA nomenclature, these studies will help inform and guide the debate surrounding sJIA and how it should be classified,” wrote researchers led by Michael Ombrello of the U.S. Department of Health and Human Services.

The Study

The study was conducted through the International Childhood Arthritis Genetics consortium, this was a genome-wide association study with 770 cases of systemic juvenile idiopathic arthritis from nine countries and 6,947 controls. Children were matched based on geography and ancestry, yielding nine case-control strata. Genomic DNA was extracted from samples and genotyped using Human Omni1M arrays (Illumina). Various statistical techniques were used to compare the genetic architecture of systemic juvenile idiopathic arthritis to other forms juvenile idiopathic arthritis.

Major findings demonstrated that two novel susceptibly loci met genome-wide significance for association with systemic juvenile idiopathic arthritis: single nucleotide polymorphisms in the class II major histocompatibility complex locus and single nucleotide polymorphisms on chromosome 1. Additionally, 23 other candidate loci were suggestive of association with systemic juvenile idiopathic arthritis.

“The identification of these loci is an important step towards the elucidation of the specific pathways and pathogenic mechanisms in sJIA, which in turn will allow the development of therapies to more specifically target sJIA pathophysiology in affected children. Several of the susceptibility loci that warrant further investigation include strong candidates for therapeutic modulation, and many novel loci or genes that have been poorly studied, to date,” Dr. Ombrello and colleagues wrote.

Recommended Next Steps

More research is needed to better understand the underlying mechanisms of systemic juvenile idiopathic arthritis and its genetic associations. New classification frameworks for juvenile idiopathic arthritis should also be explored.

Disclosures:

This study was supported in part by the Intramural Research Programs of the National Institute of Arthritis and Musculoskeletal and Skin Diseases, and the National Human Genome Research Institute of the National Institutes of Health.

References:

Michael Ombrello, Victoria Arthur, Elaine Remmers, et. al. “Genetic architecture distinguishes systemic juvenile idiopathic arthritis from other forms of juvenile idiopathic arthritis: clinical and therapeutic implications.” Annals of the Rheumatic Diseases. Published online December 7, 2016. DOI: 10.1136/annrheumdis-2016-210324

Juvenile Arthritis. American College of Rheumatology. http://www.rheumatology.org/I-Am-A/Patient-Caregiver/Diseases-Conditions/Juvenile-Arthritis. Updated June 2015. Accessed December 24, 2016.