A specific mutation in the MEFV gene, which has been linked to inflammation, may be a risk factor for developing systemic juvenile idiopathic arthritis (sJIA), a study in China suggests.

However, more research is needed to validate these findings, and assess whether the mutation impacts disease severity.

The study, “The association of MEFV gene mutations with the disease risk and severity of systemic juvenile idiopathic arthritis,” was published in the journal Pediatric Rheumatology.

The MEFV gene codes for a protein called pyrin, which is thought to keep inflammation under control. Mutations in MEFV are the cause of an inflammatory disease called familial Mediterranean fever (FMF).

Many common symptoms of sJIA, such as fever and joint pain, also are frequent in FMF, which has led to misdiagnosis. As such, researchers in China hypothesized that MEFV mutations might play a role in sJIA.

To learn more, the team analyzed the sequence of the MEFV gene in 57 children with sJIA and in 2,573 healthy people (controls). Among those with childhood arthritis, who were recruited from January 2011 to August 2018, the median age at sJIA onset was nearly 6.4 years; median follow-up duration was 54 months. These patients had a median of five affected joints.

Seven MEFV mutations were identified. The most common, E148Q, was detected in about a quarter of children both with and without sJIA. All patients with the E148Q mutation were heterozygous, meaning that the mutation was found in only one of the two gene copies — each person inherits one copy from each parent.

Statistical analyses did not indicate any significant associations between MEFV mutations and sJIA risk.

To draw more definitive conclusions, the researchers then combined their data with the findings of six previous studies that also assessed MEFV mutations in sJIA. Notably, three of these studies addressed adult onset Still’s disease (AOSD), another rare type of inflammatory arthritis. However, the similar disease processes, genetic backgrounds, and complications in sJIA and AOSD led the team to pool all of the studies in the same analysis.

Those results revealed that one MEFV mutation, termed M694V/I, was associated with a more than seven times greater risk of sJIA/AOSD. Other mutations in MEFV were not significantly associated with disease risk.

“This study suggests that the mutation p.M694V/I in MEFV gene might be a risk factor for sJIA/AOSD,” the researchers wrote.

All but one of the studies that investigated the mutation involved people living in countries around the Mediterranean. “Therefore, we should be cautious to extend the conclusions to other populations,” they wrote.

Among the children with sJIA included in the original analysis, 28 had no MEFV mutations, while 18 had one such mutation, and 11 had more than one. Patients with one mutation had significantly shorter disease activity than children with more mutations.

A subsequent analysis that accounted for variables such as age at disease onset and time to treatment initiation did not find significant associations between the number of MEFV mutations and any disease activity parameter. The researchers said this may be due to the small number of participants in the study, pointing to a need for further investigation.