Validation of calculated globulin (CG) as a screening test for antibody deficiency in an Italian University Hospital

Background: Morbidity and mortality of primary and secondary antibody deficiencies (AD) are frequently associated with diagnostic delays. These could be avoided by a combination of factors including a widespread and effective development in screening tests. Methods: Calculated globulin (CG), derived from the difference between serum total protein and albumin levels, reflects immunoglobulin serum levels and has shown to have a predictive value in the early diagnosis of antibody deficiencies. This study investigated the possibility to use low levels of CG to detect antibody deficiency in an Italian University Hospital. Results: First, we conducted an analysis of anonymized adult samples collected at our biochemistry laboratory with a range of calculated globulin levels from 15 to 22 g/l. A CG cut-off of 19 g/l detected subjects with IgG lower than 600 mg/dl with a sensitivity of 70% and a specificity of 75%. To further verify the clinical usefulness of CG, we retrospectively evaluated the relationship between CG values and serum IgG levels in 38 patients diagnosed with CVID at our Institution. Using a CG cut-off of 19 g/l, we detected antibody deficiency in 97.3% (37/38) of the subjects present in our cohort. Conclusion: Finally, we chose a CG value of 19 g/l as the cut-off for a prospective AD screening program. The results of this study show that a screening CG test can be used as a tool to reduce diagnostic delays, improve long-term prognosis and reduce the healthcare costs of antibody deficiency.