Differences between total IgG and sum of the IgG subclasses in clinical samples

Area of Science:

• Immunology
• Clinical Chemistry

Background:

• Immunoglobulin G (IgG) subclass measurement is crucial for diagnosing immunodeficiency and autoimmune diseases.
• Discrepancies between the sum of IgG subclasses (IgGsum) and total IgG can occur in patient samples.
• Understanding the frequency and magnitude of these discrepancies is important for accurate clinical interpretation.

Purpose of the Study:

• To determine the frequency and degree of discrepancies between IgGsum and total IgG in routine clinical samples.
• To investigate the relationship between IgG subclass differences and IgG1 levels.
• To evaluate the impact of sample dilution on observed discrepancies.

Main Methods:

• Retrospective analysis of 571 consecutive IgG subclass samples analyzed by nephelometric/turbidimetric assays.
• Total IgG was measured using nephelometry or turbidimetry.
• Fifty samples with >15% difference between IgGsum and total IgG were re-tested at dilution.

Main Results:

• The mean IgGsum was 3.7% higher than total IgG.
• Sixty-two samples (10.9%) exhibited a difference >15% between IgGsum and total IgG.
• The observed difference correlated with the proportion of IgG1 but not its absolute level; dilution did not significantly alter the discrepancies.

Conclusions:

• Significant discrepancies (>15%) between IgGsum and total IgG are common in routine testing.
• Implementing adjusted reference ranges based on these findings could reduce the need for additional testing.
• Samples falling outside the proposed adjusted range warrant further clinical review.