Adenosine deaminase 2 activity negatively correlates with age during childhood

Sarah M Bowers,Kristen M Gibson,Kelly L Brown,David A Cabral

doi:10.1186/s12969-020-00446-5

Abstract

BackgroundHuman adenosine deaminase 2 (ADA2) is an extracellular enzyme that negatively regulates adenosine-mediated cell signaling by converting adenosine to inosine. Altered ADA2 enzyme activity has been associated with some viral infections and rheumatic diseases. The potential utility of ADA2 as a biomarker is, however, limited by the absence of established ranges of ADA2 concentration and enzyme activity in the healthy population. It is known that ADA2 enzyme activity is lower in adults, but when (and why) this decline happens is not known. The purpose of this study was to establish normative ranges of ADA2 enzyme activity and protein concentration in the healthy pediatric population.MethodsWe modified a commercially available ADA2 enzyme activity assay to enable higher throughput analysis of fresh, frozen and hemolyzed blood samples. With this assay and ADA2 protein immunoblotting, we analyzed ADA2 enzyme activity and protein concentration in blood plasma from a cohort of children and adolescents (n = 94) aged 5 months to 18 years. One-way ANOVA with subsequent Tukey multiple comparison test was used to analyze group differences. Reference intervals were generated using the central 95% of the population (2–97.5 percentiles).ResultsADA2 enzyme activity was consistent in fresh, frozen, and hemolyzed sera and plasma as measured by our modified assay. Analysis of plasma samples from the healthy pediatric cohort revealed that ADA2 enzyme activity is significantly lower in older children than in younger children (p < 0.0001). In contrast, there was no significant correlation between ADA2 protein concentration and either age or ADA2 enzyme activity.ConclusionWe observed that ADA2 enzyme activity, but not ADA2 protein concentration, negatively correlates with age in a cohort of children and adolescents. Our findings stress the importance of appropriate age-matched controls for assessing ADA2 enzyme activity in the clinical setting.

Highlights

Human adenosine deaminase 2 (ADA2) is an extracellular enzyme that negatively regulates adenosine-mediated cell signaling by converting adenosine to inosine
Adenosine deaminase 2 (ADA2) activity has been studied in a number of adult rheumatic conditions and increased adenosine deaminase activity is observed in individuals with rheumatoid arthritis (RA) [13, 14], systemic lupus erythematous (SLE) [15], and Crohn’s disease [16]
We performed the assay over a time course from 10 min to 8 h (Supplementary Figure 2A – 2B, Additional file 1) using sera and plasma from healthy individuals and from children with abrogated ADA2 enzyme activity due to Deficiency of ADA2 (DADA2) [21]

Summary

Introduction

Human adenosine deaminase 2 (ADA2) is an extracellular enzyme that negatively regulates adenosine-mediated cell signaling by converting adenosine to inosine. ADA2 activity has been studied in a number of adult rheumatic conditions and increased adenosine deaminase activity is observed in individuals with rheumatoid arthritis (RA) [13, 14], systemic lupus erythematous (SLE) [15], and Crohn’s disease [16]. ADA2 enzyme activity is elevated and may be used as a diagnostic tool for tuberculosis [17] and HIV [18] infection, as well as for assessing benign versus malignant tumors [19]. These data suggest a regulatory role for ADA2 in inflammation and a potential to develop ADA2 as a diagnostic or disease activity biomarker for inflammatory diseases

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