Genetic Link Found Between Pediatric and Adult Arthritis

Researchers writing in Annals of the Rheumatic Diseases say they have identified a link between juvenile idiopathic arthritis and adult rheumatoid arthritis.

The study demonstrated the value of using genetic data for better understanding associations within categories of juvenile idiopathic arthritis and confirmed that some juvenile idiopathic arthritis categories share genetic links with adult disease. New knowledge about genetic associations for juvenile idiopathic arthritis may inform future treatments, improve the current classification system, and facilitate better transitions of care from child to adult clinical services.

“We identified category-specific associations and have demonstrated for the first time that rheumatoid factor (RF)-negative polyarticular JIA and oligoarticular JIA are genetically similar in their HLA associations. We also observe that each JIA category potentially has an adult counterpart,” wrote researchers led by Anne Hinks of University of Manchester in the United Kingdom.

Treating juvenile idiopathic arthritis remains a challenge for pediatric rheumatologists because it is a diverse set of diseases with seven mutually exclusive categories. Some categories of juvenile idiopathic arthritis have adult counterparts with similar clinical characteristics. For example, enthesitis-related arthritis and adult ankylosing spondylitis have a corresponding relationship.

Prior research has shown a genetic link between juvenile idiopathic arthritis and major histocompatibility region on chromosome 6; however, sample sizes and genetic approaches have been limited. Today, robust imputation methods for genotyping array data are available for classical human leucocyte antigen alleles and amino acids. In the current study, researchers used this technique to evaluate genetic associations within juvenile idiopathic arthritis categories and compare these associations with adult inflammatory arthritis.

The Study

This study was conducted with 5,043 juvenile idiopathic arthritis cases and 14,430 controls from the United Kingdom, United States, Norway, Canada and Germany. Genotype data from human leucocyte antigen region using ImmunoChip were used to impute single-nucleotide polymorphisms.

A major finding was that there were within-category associations for juvenile idiopathic arthritis. Specifically, the study team found that rheumatoid factor (RF)-negative polyarticular and oligoarticular were genetically similar. Comparisons with adult disease showed a shared association of human leucocyte antigen-DRB1 amino acid at position 13 for both child-onset and adult diseases. Moreover, researchers found that associations from a combined dataset for juvenile idiopathic arthritis types oligoarthritis and RF-negative polyarthritis were the same associations seen in adult seronegative rheumatoid arthritis.'

“The results of this study have important implications for understanding disease pathogenesis, aetiology and potential future therapeutic strategies for JIA categories,” Dr. Hinks and colleagues wrote.

Recommended Next Steps

More genetic studies are needed to fully understand novel pathways of arthritis and identify targeted therapies for child-onset and adult-onset inflammatory arthritis. Future research in this area may make it possible for data from adult clinical trials to be generalized to pediatric populations.

Disclosures:

This research was supported in part by the Wellcome Trust; National Institutes of Health; National Institute for Health Research; Doris Duke Charitable Foundation; Sparks UK; Arthritis Research UK; Medical Research Council; Canadian Institutes of Health Research; Liaison Committee between the Central Norway Regional Health Authority and the Norwegian University of Science and Technology; NIH Federal Ministry of Education and Research, Germany; Juvenile Diabetes Research Foundation International; and Texas Scottish Rite Hospital for Children.

References:

A Hinks, J Bowes, J Cobb, et. al. “Fine-mapping the MHC locus in juvenile idiopathic arthritis (JIA) reveals genetic heterogeneity corresponding to distinct adult inflammatory arthritic diseases.” Annals of the Rheumatic Diseases. Published online December 20, 2016. DOI: 10.1136/annrheumdis-2016-210025