One Step Closer for Macrophage Activation Syndrome Testing in Juvenile Arthritis

Researchers reporting at the annual meeting of the American College of Rheumatology earlier this month say they have successfully identified a specific biomarker for macrophage activation syndrome (MAS), a complication of childhood rheumatic disease most often affecting children with systemic juvenile idiopathic arthritis (sJIA).The finding could aid in the prompt diagnosis and treatment of children with this condition which can lead to multi-organ failure and is potentially life threatening.Presented by Pui Lee, M.D., Ph.D., of Boston Children's Hospital, the biomarker-adenosine deaminase 2 (ADA2)-was found to be present within the upper limits of normal in the peripheral blood of children with systemic JIA who had been diagnosed MAS. It was mildly elevated in some patients with SLE and juvenile dermatomyositis.The study included 120 children with multiple forms of juvenile idiopathic arthritis, 13 with systemic lupus erythematosus, 13 with juvenile dermatomyositis and 25 with Kawasaki disease. The results were compared to a group of 175 children without rheumatic disease.n two independent sJIA cohorts, ADA2 activity beyond the upper limit of normal effectively distinguished MAS from active sJIA without MAS, with combined sensitivity = 86% and specificity = 93%.ADA2 activity beyond the upper limit of normal distinguished systemic JIA with MAS from systemic JIA without MAS. Once MAS was successfully treated and resolved, ADA2 levels normalized.Dr. Lee and colleagues described their findings in a conference abstract: “In systemic JIA patients, ADA2 levels correlated closely with other biomarkers of MAS including ferritin, interleukin (IL)-18, and the interferon (IFN)-γ-inducible chemokine CXCL9.  In peripheral blood mononuclear cells, ADA2 was strongly induced by IL-12, IL-18 and IFN-γ. Monocytes were the primary ADA2 source in peripheral blood, with hemophagocytes a prominent source of ADA2 in MAS bone marrow as assessed by confocal microscopy.”The findings may aid in development of formalized testing for ADA2.“While there are many markers currently used for evaluation of MAS, many of them lack specificity unless the cut-off is raised significantly to distinguish MAS from general inflammation. In contrast, elevation of ADA2 levels above the normal limit of healthy individuals has good sensitivity and specificity for diagnosing MAS. This is likely related to the biology of ADA2 as a direct product of activated macrophages. It is our hope that ADA2 testing will be become more available as a clinical test to help diagnose MAS rapidly, which will in turn facilitate treatment initiation and improve patient outcomes,” Dr. Lee stated in a news release.

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ACR 2019 annual meeting, abstract #920