Expanding the diagnostic toolbox for complex genetic immune disorders.

Abstract

Laboratory-based immunology evaluation is essential to the diagnostic workup of patients with complex immune disorders, and is as essential, if not more so, depending on the context, as genetic testing, because it enables identification of aberrant pathways amenable to therapeutic intervention and clarifies variants of uncertain significance. There have been considerable advances in techniques and instrumentation in the clinical laboratory in the past 2 decades, although there are still "miles to go." One of the goals of the clinical laboratory is to ensure advanced diagnostic testing is widely accessible to physicians and thus patients, through reference laboratories, particularly in the context of academic medical centers. This ensures a greater likelihood of translating research discoveries into the diagnostic laboratory, on the basis of patient care needs rather than a sole emphasis on commercial utility. However, these advances are under threat from burdensome regulatory oversight that can compromise, at best, and curtail, at worst, the ability to rapidly diagnose rare immune disorders and ensure delivery of precision medicine. This review discusses the clinical utility of diagnostic immunology tools, beyond cellular immunophenotyping of lymphocyte subsets, which can be used in conjunction with clinical and other laboratory data for diagnosis as well as monitoring of therapeutic response in patients with genetic immunologic diseases.