Genomic tests will help early diagnosis and targeted treatment of JIA

A new genomic risk score (GRS) for juvenile idiopathic arthritis (JIA) has the potential to help children with pain get faster access to the right treatments, rheumatologists have shown.

An international group of researchers led by Australians developed an overall JIA GRS using machine learning in a large UK cohort of cases and controls and validated the score in two smaller US and Australian datasets.

Seven subtype-specific GRSs were also constructed for systemic arthritis, oligoarthritis, rheumatoid-factor-positive polyarthritis (RF-positive), rheumatoid-factor-negative polyarthritis (RF-negative), enthesitis-related arthritis (ERA), psoriatic arthritis and undifferentiated arthritis.

The study, published in Annals of Rheumatic Diseases, found the overall GRS alone could predict JIA in the validation cohorts with odds ratios of 1.831 and 2.008, respectively.

And the strongest subtype-specific GRS were those for oligoarthritis, the most commonly reported JIA subtype, and ERA, the JIA subtype which incurs the longest time to referral to a paediatric rheumatologist.

“Given the cost effectiveness of a genotyping array and the time-invariant properties of germline DNA, these JIA GRSs hold promise for rapid clinical translation as means of diagnosis and risk stratification,” the study authors said.

“At-risk children can be non-invasively stratified as high-risk much earlier in the diagnostic pathway, and children with low risk non-inflammatory disease can be appropriately triaged and managed earlier.”

Joint senior author on the study, paediatric rheumatologist Professor Jane Munro from the Royal Children’s Hospital Melbourne and the Murdoch Children’s Research Institute, told the limbic that non-inflammatory conditions in children such as growing pains and sports injuries contributed to a diagnostic delay in JIA.

“Often they take a long time to get to the right clinicians …[it] would be really great if we had quite a cheap test out in the community at the primary care level. So that’s really the purpose of this study,” she said.

“The risk score is really aimed at helping that early diagnosis and getting early treatment by getting people to the right doctors at the right time.”

“I think the initial aim is trying to assist with a genomic risk score at the GP level and as this evolves and we get larger case sets we may be able to help the whole specialty understand the subtypes at the biology level better.”

Professor Munro said Australia had just 23 paediatric rheumatologists.

“So there is not a huge workforce and the same thing internationally. Some states in America don’t have a paediatric rheumatologist. In Asia Pacific and in Africa, there is a huge workforce gap.”

“So in some parts of the world you can imagine, if we could screen out children who don’t have inflammatory disease, then we could at least target who we need to see.”

She said physiotherapists, orthopaedic and sports medicine physicians, and paediatricians could be dealing with the non-inflammatory conditions while rheumatologists focussed on the children requiring immunosuppressive medications for their JIA.

Associate Professor Michael Inouye, head of systems genomics at the Baker Heart & Diabetes Institute, was the other joint senior author on the study.

The genetic variants and weights of the JIA GRS are publicly available via the Polygenic Score Catalog.

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