Inborn errors of immunity (IEI) represent a wide spectrum of primary immunodeficiencies (PID) and immune dysregulatory diseases, often with underlying genetic causes. PID genetic panels permit better characterization of a patient’s underlying immune abnormality, potentially leading to improved treatment. We analyzed the demographics of patients undergoing genetic testing, how successfully genetic causes for IEI were identified, and whether a genetic diagnosis changed patient treatment and care.
We categorized patients into phenotypes based on clinical presentation and supporting non-molecular laboratory tests, then assessed whether treatment/care changed after genetic testing via next generation sequencing of PID gene panels.
From 2013-2018, 105 complex patients (80% of whom were followed by multidisciplinary teams) received immunologic genetic testing, while having the following clinical phenotypes based on IUIS categories: Immune Dysregulation (27%); Predominantly Antibody Deficiencies (24%), Autoinflammatory (13%); Combined Immunodeficiency (14%); Complement Deficiency (2%); Phagocyte Deficiency (3%), and uncategorized (16%). 8% of the patients had various malignancies. Potential genetic abnormalities (predicted disease-causing variant related to clinical phenotype) were detected in 44/105 (42%) patients; 22 of these (21% of all patients) received a molecular diagnosis. Clinical diagnosis changed for 15/22 patients diagnosed molecularly and for 2/20 patients with a variant of unknown significance (VoUS). Altogether, 29 patients underwent management changes, and 11/42 patients with significant molecular findings underwent further functional testing of their immune system.
Genetic panel testing, a continually evolving diagnostic tool, provided valuable, treatment-guiding information for 25% of the immunologically complex patients in this cohort. VoUS, especially if consistent with clinical phenotype, remain clinical challenges.