Implementing calculated globulin screening for immunodeficiencies: The benefits and challenges

There is a need for pragmatic and cost-effective methodologies to facilitate earlier diagnosis of patients with primary and secondary immunodeficiencies, who often experience diagnostic delays that impact their quality of life, morbidity, and mortality. This review article will consider the utility of calculated globulin (CG) as a simple and unbiased screening tool for immunodeficiencies. We review literature indicating that CG can serve as an inexpensive and routinely performed proxy for immunoglobulin levels due to their established correlation. We also set out a workflow for the implementation of CG into clinical practice and discuss optimal approaches to embedding into laboratory reporting systems, and integration of AI approaches could expedite diagnoses. Finally, we discuss the challenges and pitfalls of CG screening, including the need for established CG cutoffs/action values across different patient age cohorts. Collaboration among biochemistry and immunology laboratories, clinicians, and patient organizations will be required to manage the logistics of effective broader implementation of CG screening into clinical practice.