Novel innate immune variants causing autoinflammatory disease

We manage the Australian Autoinflammatory Disease Registry (AADRY.org), and collaborate widely to identify genetic variants that may be the cause of chronic inflammatory disease for patients from all over Australia. We now have several candidate variants of interest that we need to test to see if they are pathogenic, which could represent a novel mechanism, or in some cases the first time the disease has been identified. Given that Autoinflammatory diseases primarily feature inflammation from innate immune cells, we frequently examine the effect of the genetic variant using CRISPR in relevant cell lines (eg. monocytes) using readouts such as cytokine production (eg. ELISA or QPCR). More specific tests may need to be applied depending on the gene of interest. All results are confirmed using primary samples from patients (eg PBMC) where possible. At the conclusion of this project it should be possible to confirm the pathogenicity of a particular variant for a patient or family with Autoinflammatory disease, and add to the list of genes that are known to cause these conditions.