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Adenosine deaminase 2 as a biomarker of macrophage activation syndrome in systemic juvenile idiopathic arthritis.

Publication ,  Journal Article
Lee, PY; Schulert, GS; Canna, SW; Huang, Y; Sundel, J; Li, Y; Hoyt, KJ; Blaustein, RB; Wactor, A; Do, T; Halyabar, O; Chang, MH; Dedeoglu, F ...
Published in: Ann Rheum Dis
February 2020

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.

Duke Scholars

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Published In

Ann Rheum Dis

DOI

EISSN

1468-2060

Publication Date

February 2020

Volume

79

Issue

2

Start / End Page

225 / 231

Location

England

Related Subject Headings

  • Sensitivity and Specificity
  • Reference Values
  • Mucocutaneous Lymph Node Syndrome
  • Male
  • Macrophage Activation Syndrome
  • Lupus Erythematosus, Systemic
  • Interleukin-18
  • Intercellular Signaling Peptides and Proteins
  • Humans
  • Ferritins
 

Citation

APA
Chicago
ICMJE
MLA
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Lee, P. Y., Schulert, G. S., Canna, S. W., Huang, Y., Sundel, J., Li, Y., … Nigrovic, P. A. (2020). Adenosine deaminase 2 as a biomarker of macrophage activation syndrome in systemic juvenile idiopathic arthritis. Ann Rheum Dis, 79(2), 225–231. https://doi.org/10.1136/annrheumdis-2019-216030
Lee, Pui Y., Grant S. Schulert, Scott W. Canna, Yuelong Huang, Jacob Sundel, Ying Li, Kacie J. Hoyt, et al. “Adenosine deaminase 2 as a biomarker of macrophage activation syndrome in systemic juvenile idiopathic arthritis.Ann Rheum Dis 79, no. 2 (February 2020): 225–31. https://doi.org/10.1136/annrheumdis-2019-216030.
Lee PY, Schulert GS, Canna SW, Huang Y, Sundel J, Li Y, et al. Adenosine deaminase 2 as a biomarker of macrophage activation syndrome in systemic juvenile idiopathic arthritis. Ann Rheum Dis. 2020 Feb;79(2):225–31.
Lee, Pui Y., et al. “Adenosine deaminase 2 as a biomarker of macrophage activation syndrome in systemic juvenile idiopathic arthritis.Ann Rheum Dis, vol. 79, no. 2, Feb. 2020, pp. 225–31. Pubmed, doi:10.1136/annrheumdis-2019-216030.
Lee PY, Schulert GS, Canna SW, Huang Y, Sundel J, Li Y, Hoyt KJ, Blaustein RB, Wactor A, Do T, Halyabar O, Chang MH, Dedeoglu F, Case SM, Meidan E, Lo MS, Sundel RP, Richardson ET, Newburger JW, Hershfield MS, Son MB, Henderson LA, Nigrovic PA. Adenosine deaminase 2 as a biomarker of macrophage activation syndrome in systemic juvenile idiopathic arthritis. Ann Rheum Dis. 2020 Feb;79(2):225–231.

Published In

Ann Rheum Dis

DOI

EISSN

1468-2060

Publication Date

February 2020

Volume

79

Issue

2

Start / End Page

225 / 231

Location

England

Related Subject Headings

  • Sensitivity and Specificity
  • Reference Values
  • Mucocutaneous Lymph Node Syndrome
  • Male
  • Macrophage Activation Syndrome
  • Lupus Erythematosus, Systemic
  • Interleukin-18
  • Intercellular Signaling Peptides and Proteins
  • Humans
  • Ferritins