Enhanced clinical decision-making to optimize targeted gene panel testing for inborn errors of immunity

Area of Science:

• Immunology
• Genetics
• Pediatrics

Background:

• Targeted gene panels (TGPs) are increasingly utilized for diagnosing inborn errors of immunity (IEI) due to advancements in understanding monogenic causes.
• Optimizing the clinical indications for TGPs can improve diagnostic test yields.

Purpose of the Study:

• To identify clinical factors associated with positive diagnostic results from targeted gene panels (TGPs) in pediatric patients suspected of having inborn errors of immunity (IEI).

Main Methods:

• A retrospective analysis was conducted on 350 pediatric patients with suspected IEI who underwent TGP testing over five years at a US tertiary hospital.
• Data included patient demographics, clinical diagnoses, and genetic testing outcomes.

Main Results:

• 8.3% of patients received diagnostic genetic testing results (pathogenic or likely pathogenic variants).
• Diagnostic yield was significantly higher for patients with positive severe combined immunodeficiency (SCID) newborn screens (OR 10.21), and clinical diagnoses of combined immunodeficiency (CID) (OR 11.85) or SCID (OR 51.2).
• Immune dysregulation without infections, coupled with multiple autoimmune conditions or non-atopic skin lesions, also correlated with higher diagnostic rates.

Conclusions:

• Genetic testing via TGPs should be strongly considered for pediatric patients presenting with a positive newborn SCID screen.
• Patients with clinical diagnoses of CID or SCID, and those exhibiting immune dysregulation with multiple autoimmune conditions or non-atopic skin lesions, warrant genetic evaluation for IEI.