Miss Loryn Halliday

Research project: The influence of adenosine deaminase 2 (ADA2) on the endothelium

Abstract

Adenosine deaminase 2 deficiency (DADA2) was first reported in 2014, and identified in children with symptoms of early-onset strokes, livedo rashes and systematic vasculopathy, which did not equate to any known familial autoinflammatory diseases.  Studies to date have shown that the disease onset can be as young as 2 months old and the severity of the clinical manifestations can vary; children with the most serve cases are reported to have died before their first birthday.  Whilst inflammation and vascular pathology have been linked to ADA2 deficiency due to the symptoms presented, the mechanism is not understood.  Therefore, it is of importance to understand ADA2's role and its interactions with adenosine, the endothelium and leukocytes.  This in turn may also provide knowledge for the most suitable treatments for this group of patients, who do not respond well to conventional steroid treatment.

Thus far, research into ADA2 has shown a wide range of clinical manifestations, a range of mutations in the ADA2 gene, the need for asymptomatic patients to be closely monitored or treated, and the diagnostic potential of ADA2 for vasculitis.  This study aims to look at: whether ADA2 is having a direct effect on the endothelium, which adenosine receptors and downstream pathways are involved, how does this cause the disease pathology seen in ADA2 deficiency.  Whilst DADA2 is a rare condition, it can have fatal results for the children affected and this research aims to provide insight as to the most effective treatment for both, symptomatic and asymptomatic patients.