# Improving screening for antibody deficiency using calculated globulin and serum protein electrophoresis

## TL;DR

This study identifies optimal thresholds for calculated globulin and serum protein electrophoresis to screen for antibody deficiencies like CVID in adults and adolescents.

## Contribution

The study establishes age-specific cut-offs for calculated globulin and gammaglobulins to detect hypogammaglobulinemia in hospitalized patients.

## Key findings

- A CG cut-off of 22 g/L detected 80% of hypogammaglobulinemia cases with 87% specificity.
- Gammaglobulin cut-off of 8.9 g/L achieved 96% sensitivity and 88% specificity.
- CG and gammaglobulin levels correlated strongly with IgG levels, explaining up to 75% of the variance.

## Abstract

Antibody deficiencies, particularly Common Variable Immunodeficiency (CVID), represent a major health concern due to comorbidities linked to delayed diagnosis. Calculated globulin (CG) and the gammaglobulins derived from serum protein electrophoresis have been proposed as reliable indices for screening hypogammaglobulinemia. This study aimed to establish optimal cut-offs for CG and the gammaglobulins to identify patients with low IgG among hospitalized adolescents and adults from Algeria.

Serum samples and clinical data were collected from hospitalized patients aged over 10 years. Total protein and albumin were determined by the biuret and bromocresol green methods, IgG was quantified by nephelometry, and gammaglobulins were determined by gel or capillary serum protein electrophoresis. In addition, a control group was included for cut-off verification.

A total of 980 patients were recruited, including 762 adults (≥ 18 years) and 218 adolescents (10–17 years), with a median age of 47 years. The control group comprised 20 patients with confirmed CVID. The most frequent clinical manifestations were autoimmune disorders (33%), inflammatory disorders (31%), and severe infections (24%). Hypogammaglobulinemia was identified in 94 patients, including 6 with primary causes. IgG levels correlated significantly with both CG and gammaglobulins. Linear regression analysis showed that IgG accounted for 49% of the variance in CG and 75% in the gammaglobulins. A CG cut-off value of 22 g/L yielded a sensitivity of 80% and a specificity of 87%, whereas a gammaglobulin cut-off of 8.9 g/L achieved a sensitivity of 96% and a specificity of 88%. Gammaglobulin cut-off values were consistent between adult and pediatric groups, while differences in CG cut-offs were observed (adult group: 22.25 g/L; pediatric group: 24.15 g/L). Thirteen of the 20 patients with CVID in the control group (65%) had a CG level below 22 g/L.

CG and serum protein electrophoresis are reliable tools for screening hypogammaglobulinemia. Although both tests demonstrated satisfactory sensitivity and specificity, certain cases may be underestimated or overestimated. Therefore, thorough clinical evaluation and, whenever possible, direct immunoglobulin measurement remain essential.