PT  - JOURNAL ARTICLE
AU  - Pui Y Lee
AU  - Grant S Schulert
AU  - Scott W Canna
AU  - Yuelong Huang
AU  - Jacob Sundel
AU  - Ying Li
AU  - Kacie J Hoyt
AU  - Rachel B Blaustein
AU  - Alexandra Wactor
AU  - Thuy Do
AU  - Olha Halyabar
AU  - Margaret H Chang
AU  - Fatma Dedeoglu
AU  - Siobhan M Case
AU  - Esra Meidan
AU  - Mindy S Lo
AU  - Robert P Sundel
AU  - Edward T Richardson
AU  - Jane W Newburger
AU  - Michael S Hershfield
AU  - Mary Beth Son
AU  - Lauren A Henderson
AU  - Peter A Nigrovic
TI  - Adenosine deaminase 2 as a biomarker of macrophage activation syndrome in systemic juvenile idiopathic arthritis
AID  - 10.1136/annrheumdis-2019-216030
DP  - 2020 Feb 01
TA  - Annals of the Rheumatic Diseases
PG  - 225--231
VI  - 79
IP  - 2
4099  - http://ard.bmj.com/content/79/2/225.short
4100  - http://ard.bmj.com/content/79/2/225.full
SO  - Ann Rheum Dis2020 Feb 01; 79
AB  - Objective Macrophage activation syndrome (MAS) is a life-threatening complication of systemic juvenile idiopathic arthritis (sJIA) characterised by a vicious cycle of immune amplification that can culminate in overwhelming inflammation and multiorgan failure. The clinical features of MAS overlap with those of active sJIA, complicating early diagnosis and treatment. We evaluated adenosine deaminase 2 (ADA2), a protein of unknown function released principally by monocytes and macrophages, as a novel biomarker of MAS.Methods We established age-based normal ranges of peripheral blood ADA2 activity in 324 healthy children and adults. We compared these ranges with 173 children with inflammatory and immune-mediated diseases, including systemic and non-systemic JIA, Kawasaki disease, paediatric systemic lupus erythematosus and juvenile dermatomyositis.Results ADA2 elevation beyond the upper limit of normal in children was largely restricted to sJIA with concomitant MAS, a finding confirmed in a validation cohort of sJIA patients with inactive disease, active sJIA without MAS or sJIA with MAS. ADA2 activity strongly correlated with MAS biomarkers including ferritin, interleukin (IL)-18 and the interferon (IFN)-γ-inducible chemokine CXCL9 but displayed minimal association with the inflammatory markers C reactive protein and erythrocyte sedimentation rate. Correspondingly, ADA2 paralleled disease activity based on serial measurements in patients with recurrent MAS episodes. IL-18 and IFN-γ elicited ADA2 production by peripheral blood mononuclear cells, and ADA2 was abundant in MAS haemophagocytes.Conclusions These findings collectively identify the utility of plasma ADA2 activity as a biomarker of MAS and lend further support to a pivotal role of macrophage activation in this condition.