LAUSR

We thank Gao and colleagues for their interest in our recent study on adenosine deaminase 2 (ADA2) as a biomarker of macrophage activation syndrome.1 In their letter, the authors demonstrated a strong correlation between total adenosine deaminase (tADA) and ADA2 levels in the peripheral blood of healthy controls and patients with immune-mediated diseases.2 They suggest that, as it is easier to measure tADA than ADA2 activity, tADA activity alone would be suitable as a diagnostic marker. Because tADA is the sum of ADA1 and ADA2 activity, the biology of both ADA isoforms should be considered in evaluating this claim. Among several differences between ADA1 and ADA2, two are relevant to their assay in clinical laboratories: the affinity of ADA1 for adenosine is 100-fold greater than that of ADA2, and ADA1 is inhibited by the analogue erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA), but ADA2 is not.3 Plasma ADA2 activity is therefore performed at a saturating adenosine concentration that is ~10 000-fold higher than physiological, and in the presence of EHNA to inhibit ADA1. Under these in vitro conditions, ADA2 accounts for the majority of measured ADA activity in plasma. The correlation between …