Precision diagnostics for pediatric hyperinflammatory syndromes

Pediatric hyperinflammatory syndromes represent a heterogenous group of life-threatening disorders associated with impaired immunity and excessive inflammation. A majority of patients lack a molecular diagnosis and treatments of these conditions are not standardized. There is a critical need for personalized medicine.

Building on advanced clinical pipelines and unique patient samples, the specific aims of our proposal are to (1) establish systematic, longitudinal sampling and analyses of pediatric patients with suspected primary immunodeficiency disease (PID), (2) establish systems to evaluate protein-coding variants of unknown significance in genes associated with the most severe PID, (3) identify new PIDs through cutting-edge functional genomic analyses, and (4) determine and understand the pathophysiological mechanisms of novel hyperinflammatory disorders with poor clinical outcome.

Our innovative approach combines unique patient material with advanced bioinformatic algorithms and cellular methodology.

This proposal is supported by the pioneering translational immunological expertise of the lead investigator and will benefit from a worldwide network of collaborators.

Ultimately, we will identify novel molecular causes of hyperinflammatory syndromes which can facilitate personalized medicine.

It will also provide proof-of-concept methodology that can be employed in the diagnostics of other unexplained patients with suspected monogenic disease.