Australian Autoinflammatory Diseases Registry (AADRY): A national approach to the genetic and immunological evaluation of patients with suspected autoinflammatory disease. [Internal Medicine Journal.]

Abstract

Traditionally defined as periodic fever syndromes lacking markers of autoimmunity such as high titre self-reactive T cells and auto-antibodies, the spectrum of monogenic autoinflammatory diseases has broadened substantially in recent years. The clinical heterogeneity of newly described conditions such as STING associated vasculopathy with onset in infancy (SAVI) and Deficiency in ADA2 (DADA2) has forced reconsideration of traditional designations, with the common link between these disorders being inappropriate inflammation and cytokine dysregulation. These new diagnoses can be attributed to the introduction of whole exome sequencing (WES) into the diagnostic algorithm of patients with suspected, but currently genetically undefined, autoinflammatory diseases. We believe it's important to take a national approach to the diagnosis of autoinflammatory disorders given their rarity and introduce the establishment of AADRY, an Australian Autoinflammatory Diseases RegistrY. AADRY proposes to collect epidemiological and clinical data on patients with suspected and confirmed autoinflammatory diseases, and will perform whole exome sequencing in patients who are yet to be genetically characterised. We also aim to perform in vitro testing and harness CRISPR-Cas9 gene editing technology to determine the functional significance of novel variants and their potential contribution to clinical phenotype. We describe bioinformatic analyses and other results from the first 12 AADRY cases analysed, including one trio and one family of five.