Adenosine deaminase 2 activity negatively correlates with age during childhood
Abstract Background Human 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...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2020-07-01
|
| Series: | Pediatric Rheumatology Online Journal |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12969-020-00446-5 |
| _version_ | 1819229053801988096 |
|---|---|
| author | Sarah M. Bowers Kristen M. Gibson David A. Cabral Kelly L. Brown |
| author_facet | Sarah M. Bowers Kristen M. Gibson David A. Cabral Kelly L. Brown |
| author_sort | Sarah M. Bowers |
| collection | DOAJ |
| description | Abstract Background Human 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. Methods We 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). Results ADA2 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. Conclusion We 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. |
| first_indexed | 2024-12-23T11:07:04Z |
| format | Article |
| id | doaj.art-563e81508bbe493f807e63d614801d13 |
| institution | Directory Open Access Journal |
| issn | 1546-0096 |
| language | English |
| last_indexed | 2024-12-23T11:07:04Z |
| publishDate | 2020-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Pediatric Rheumatology Online Journal |
| spelling | doaj.art-563e81508bbe493f807e63d614801d132022-12-21T17:49:28ZengBMCPediatric Rheumatology Online Journal1546-00962020-07-011811910.1186/s12969-020-00446-5Adenosine deaminase 2 activity negatively correlates with age during childhoodSarah M. Bowers0Kristen M. Gibson1David A. Cabral2Kelly L. Brown3British Columbia Children’s Hospital Research InstituteBritish Columbia Children’s Hospital Research InstituteDepartment of Pediatrics, The University of British ColumbiaBritish Columbia Children’s Hospital Research InstituteAbstract Background Human 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. Methods We 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). Results ADA2 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. Conclusion We 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.http://link.springer.com/article/10.1186/s12969-020-00446-5Adenosine deaminase 2AdenosinePediatricsInflammation |
| spellingShingle | Sarah M. Bowers Kristen M. Gibson David A. Cabral Kelly L. Brown Adenosine deaminase 2 activity negatively correlates with age during childhood Pediatric Rheumatology Online Journal Adenosine deaminase 2 Adenosine Pediatrics Inflammation |
| title | Adenosine deaminase 2 activity negatively correlates with age during childhood |
| title_full | Adenosine deaminase 2 activity negatively correlates with age during childhood |
| title_fullStr | Adenosine deaminase 2 activity negatively correlates with age during childhood |
| title_full_unstemmed | Adenosine deaminase 2 activity negatively correlates with age during childhood |
| title_short | Adenosine deaminase 2 activity negatively correlates with age during childhood |
| title_sort | adenosine deaminase 2 activity negatively correlates with age during childhood |
| topic | Adenosine deaminase 2 Adenosine Pediatrics Inflammation |
| url | http://link.springer.com/article/10.1186/s12969-020-00446-5 |
| work_keys_str_mv | AT sarahmbowers adenosinedeaminase2activitynegativelycorrelateswithageduringchildhood AT kristenmgibson adenosinedeaminase2activitynegativelycorrelateswithageduringchildhood AT davidacabral adenosinedeaminase2activitynegativelycorrelateswithageduringchildhood AT kellylbrown adenosinedeaminase2activitynegativelycorrelateswithageduringchildhood |