Effect of ontogeny and vaccination on plasma adenosine deaminase (ADA)-1 and -2 levels across the first week of human life

Abstract

Abstract Introduction Adenosine is a purine metabolite that acts on its leukocyte receptors to inhibit inflammatory and Th1-polarizing cytokine production. Newborns exhibit lower plasma levels of adenosine deaminase (ADA), an enzyme that metabolizes extracellular adenosine, resulting in elevated plasma adenosine levels and a Th2/anti-inflammatory bias. Humans express two ADA isoforms: ADA1 and ADA2. Characterizing the impact of ontogeny and vaccination on levels of ADA1 and ADA2 may provide insight into mechanisms regulating early life immune development. Methods Newborns were recruited at the MRC Unit-Gambia and randomized to either Hepatitis B (HepB), BCG, or the combination of both vaccines. Plasma was collected at birth (day of life (DOL) 0) and at DOL 1, 3, or 7. Plasma levels of ADA1 and ADA2 were measured by a chromogenic assay. Log-transformed ADA concentrations were compared using ANOVA. Results In this interim analysis, we measured n = 51–53 participants per vaccine group per timepoint. ADA2 activity ex vivo in plasma derived from Gambian newborns increased by median fold changes of 1.6 (control), 1.6 (HepB), 1.5 (BCG), and 1.9 (HepB+BCG) over the first week of life. The changes in ADA2 for all groups were statistically significant over DOL 0. HepB and BCG immunizations were both associated with statistically significant 1.5-fold decrease in ADA1 across the first week of life. Conclusions Neonatal plasma ADA2 activity rises across the first week of life, suggestive of ontogeny-specific changes that promote Th2/anti-inflammatory immune status. Immunization at birth with HepB or BCG may be associated with lower ADA1 across the first week of life. ADA isoforms may be useful biomarkers of immune development and vaccine responses.