Genomic profiling at a single center cracks the code in inborn errors of immunity.

Abstract

Inborn errors of immunity (IEI) entail a diverse group of disorders resulting from hereditary or de novo mutations in single genes, leading to immune dysregulation. This study explores the clinical utility of next-generation sequencing (NGS) techniques in diagnosing monogenic immune defects. Eight patients attending the immunodeficiency clinic and with unclassified antibody deficiency were included in the analysis. Clinical records, immune characteristics, and family histories were reviewed, and a target gene panel (TGP) sequencing was performed to identify pathogenic variants. TGPs identified seven variants in TNFRSF13B (TACI), CARMIL2, STAT1, STAT3, and ORAI1 genes. These findings provided definitive diagnoses and proper prognostic assessment. Patients exhibited a wide range of clinical manifestations, including recurrent infections, autoimmune cytopenias, and organ-specific complications. The genetic diversity observed highlights the importance of genetic testing in diagnosing IEIs and tailoring treatments. This study underscores the role of TGPs in diagnosing IEIs, revealing significant genetic heterogeneity and phenotypic variability. They offer a precise tool for identifying underlying genetic defects, facilitating personalized medicine approaches, and eventually improving patient outcomes. The findings emphasize the need for comprehensive genetic testing to uncover novel pathogenic variants, enhancing our understanding of immune system dysfunction. NGS is a critical tool for the management of IEI, enabling precise diagnosis and personalized treatment strategies. Despite resource limitations, the progressive affordability is likely to expand its clinical utility, ultimately improving patient care and advancing the field of immunology. In the meantime, accurate phenotypic assessment is essential for resource optimization and case prioritization.