A Review of Adenosine Deaminase 2 (ADA2) as a Biomarker of Monocyte/Macrophage Activation

Adenosine deaminase 2 (ADA2) is predominantly expressed by and secreted from activated monocytes and macrophages into plasma. This review explores the utility of ADA2 as a biomarker of monocyte/macrophage activation in a range of conditions and suggests potential applications for its clinical use.

Elevated ADA2 activity has been observed in conditions associated with granulomatous inflammation and macrophage activation, including tuberculosis, sarcoidosis, and macrophage activation syndrome. This finding has also been reported in liver fibrosis, malignancy, infection, and autoimmune diseases such as rheumatoid arthritis and systemic lupus erythematosus. Absent or near absent ADA2 activity is associated with deficiency of ADA2 (DADA2), an autosomal recessive inborn error of immunity. Increased ADA2 activity correlates with monocyte/macrophage activity, making it a potential biomarker in diseases characterized by excessive macrophage activation. Although ADA2 activity is relatively easy to measure in plasma and may assist with diagnosis when conventional approaches are unavailable, invasive, or carry additional risks, it lacks disease specificity. The absence of ADA2 activity in plasma combined with a characteristic clinical phenotype and biallelic genetic mutations inADA2 is diagnostic of DADA2.