A molecular signature depicting remission from juvenile arthritis is described in the open access journal Arthritis Research & Therapy. The findings boost our understanding of the molecular processes involved in the disease, and could be used to help develop strategies to enhance remission.
Juvenile idiopathic arthritis (JIA) is an chronic inflammatory disease of unknown cause that affects around 1 in 1000 children. Remission can be achieved with the anti-rheumatic drug methotrexate and/or drugs that target immune and inflammatory processes; so-called TNF alpha blockers. But remission isn’t always permanent. Indeed clinicians don’t even know what remission is at the molecular and cellular levels.
James N. Jarvis and colleagues compared the gene expression profiles of blood cells taken from drug-treated JIA children in remission and healthy controls, highlighting numerous differences between the two groups.
Remission is a distinct biological state, they show. Children in remission express various genes that healthy children don’t, including some related to a steroid hormone receptor called hepatocyte nuclear factor 4 alpha (HNF4a). Indeed, HNF4a protein can be found in the blood cells of children with JIA.
Mutations in the HNF4a gene have been previously implicated in type 2 diabetes, but this is the first time the molecule has been implicated in arthritis. As such, it may represent a novel target for future therapies directed at JIA and adult forms of rheumatoid arthritis. It could also represent the first steps in the identification of biomarkers that predict which JIA patients are likely to respond to particular therapies.
For now, the data represent a molecular signature of remission. This in itself may have practical value. There are various ongoing clinical trials in JIA, all of which use remission as an important clinical end point. This gene expression data could help define when remission has occurred.