Quantitative Serum Immunoglobulin G (IgG) Test
Primary Purpose
Quantitative serum IgG testing measures the concentration of immunoglobulin G antibodies in blood to diagnose and manage antibody deficiency disorders, guide immunoglobulin replacement therapy, and evaluate immune function. 1
Clinical Indications for Testing
Diagnosing Primary Immunodeficiencies
IgG measurement is essential for diagnosing Common Variable Immunodeficiency (CVID), which requires IgG <450-500 mg/dL plus IgA or IgM below the 5th percentile, with impaired specific antibody production. 2
Agammaglobulinemia diagnosis requires severely reduced or absent IgG levels along with absent or severely reduced B cells, typically presenting with early-onset severe bacterial infections. 3, 2
The test helps distinguish primary immunodeficiencies (where only immunoglobulin production is affected and albumin remains normal) from secondary hypogammaglobulinemia (where both total protein and albumin are low due to protein loss). 2
Monitoring Immunoglobulin Replacement Therapy
Patients receiving intravenous or subcutaneous immunoglobulin therapy require IgG trough level monitoring monthly during initial therapy, then every 6-12 months once stable. 2
The dose of immunoglobulin replacement therapy (typically 200-800 mg/kg monthly) is adjusted based on trough IgG levels and clinical response, though infection frequency is more important than serum levels alone for assessing adequacy. 3, 2
Increasing IgG trough levels while maintaining constant dosing intervals indicates recovery of the patient's own IgG production, which may allow discontinuation of replacement therapy in transient hypogammaglobulinemia of infancy. 3
Assessing Infection Risk
Patients with IgG <300 mg/dL are at high risk for life-threatening bacterial infections and require urgent immunoglobulin replacement therapy. 2
IgG <400 mg/dL with recurrent infections (≥3 events/year) or ≥2 severe recurrent infections by encapsulated bacteria (regardless of IgG level) indicates need for immunoglobulin replacement therapy. 2
Test Composition and Normal Values
IgG normally comprises approximately 80% of total serum immunoglobulins, with IgA at 15%, IgM at 5%, IgD at 0.2%, and IgE in trace amounts. 1
The test measures total IgG protein concentration, not functional antibody activity—functional assessment requires measuring specific antibody responses to protein and polysaccharide antigens. 3, 2
Critical Diagnostic Distinctions
Primary vs. Secondary Hypogammaglobulinemia
Concurrent low total protein and albumin levels strongly suggest secondary hypogammaglobulinemia from protein loss through the gastrointestinal tract, lymphatics, or kidney, requiring evaluation for nephrotic syndrome, protein-losing enteropathy, or lymphatic disorders before diagnosing primary immunodeficiency. 2
Medications (antiepileptics, gold) and hematologic malignancies (B-cell lymphomas, multiple myeloma) can cause secondary hypogammaglobulinemia and must be excluded. 2
Combined Immunodeficiency Evaluation
Low IgG should prompt T-cell evaluation including complete blood count with differential and lymphocyte subset analysis (CD4, CD8, CD19, memory B-cell counts) to identify combined immunodeficiency. 2
B-cell enumeration by flow cytometry is essential to distinguish CVID (normal or moderately reduced B cells) from agammaglobulinemia (absent or severely reduced B cells). 3, 2
Important Limitations
Antibody values must reflect functional antibody responses rather than simply protein concentration to be clinically meaningful—quantitative IgG levels do not correlate perfectly with protection against infection. 3
The opsonophagocytic assay measuring killing of organisms by vaccine-elicited antibodies provides more valuable information than quantitative IgG measurement alone for establishing true antibody deficiency. 3
Different individuals catabolize administered immunoglobulin at different rates, so dose titration must be individualized based on maintaining infection-free status rather than achieving arbitrary IgG targets. 3
Clinical Context Requirements
Diagnosis of primary immunodeficiency requires clinical correlation with documented susceptibility to infectious diseases, particularly recurrent bacterial respiratory infections—laboratory values alone are insufficient. 3
Testing specific antibody responses to the 23-valent pneumococcal polysaccharide vaccine (comparing pre- and post-immunization titers) is considered the most definitive test of B-cell function, though this assay has significant laboratory-to-laboratory variability. 3