StemCell Therapy

Certain levels of plasma protein adenosine deaminase 2 (ADA2) are sensitive and specific, and can be used as a novel biomarker of macrophage activation syndrome in patients with systemic juvenile idiopathic arthritis (JIA), according to research results published in the Annals of the Rheumatic Diseases.

Researchers sought to evaluate the role and function of ADA2 as a novel biomarker of macrophage activation syndrome because of the overlapping clinical features between macrophage activation syndrome and active systemic JIA.

A reference range for plasma ADA2 activity was first established using samples from 324 healthy individuals (174 children and 150 adults). Spectrophotometric assays showed that patients with biallelic ADA2 mutations had a near absence of ADA2 activity compared with carriers who had approximately half-normal plasma ADA2 activity.

After establishing the reference range, the researchers compared ADA2 levels in children with Kawasaki disease, pediatric systemic lupus erythematosus, and juvenile dermatomyositis with age-matched healthy controls. Investigators established that ADA2 levels did not correlate with markers of disease activity and were not a general marker of systemic inflammation in any of the 3 disorders.

Among the JIA population, most patients showed plasma ADA2 activity levels that were comparable with age-matched healthy controls; however, a small subset had levels well above the upper limit of normal. After stratification by JIA category, investigators found that ADA2 activity was present in children with oligoarticular and polyarticular JIA, enthesitis-related arthritis, and psoriatic arthritis.

Using multiple macrophage activation syndrome biomarkers, researchers compared ADA2 activity in patients with JIA and created a correlation matrix based on Spearman rank correlation r values. The comparisons demonstrated that ADA2 levels correlated with ferritin, interleukin-18, and C-X-C Motif Chemokine Ligand 9. ADA2 activity also correlated well with increased aspartate aminotransferase levels in macrophage activation syndrome, but not with conventional markers of inflammation.

Although the patterns displayed by these markers were different, all the markers were sensitive and specific in discriminating macrophage activation syndrome from systemic JIA using the upper limit of normal as a cutoff.

Seven patients with macrophage activation syndrome had available serum samples. Consistent with previous analyses, investigators found that ADA2 levels were generally higher during a confirmed episode of macrophage activation syndrome compared with other time points. Researchers noted that patients who experienced recurrent episodes of macrophage activation syndrome exhibited ADA2 levels near the upper limit of normal even when macrophage activation syndrome was absent.

Whether ADA2 contributes to the pathophysiology of [macrophage activation syndrome] is not clear, the researchers concluded. The [physiologic] function of ADA2 remains to be determined.

Reference

Lee PY, Schulert GS, Canna SW, et al. Adenosine deaminase 2 as a biomarker of macrophage activation syndrome in systemic juvenile idiopathic arthritis [published online November 9, 2019]. Ann Rheum Dis. doi: 10.1136/annrheumdis-2019-216030

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Novel Biomarker of Macrophage Activation Syndrome Identified in Juvenile Idiopathic Arthritis - Rheumatology Advisor

This entry was posted on December 3, 2019 at 6:46 pm and is filed under Arthritis. You can follow any responses to this entry through the RSS 2.0 feed. Both comments and pings are currently closed. |