What is the Immunoglobulin G (IgG) Test Used For?
The IgG test measures the level of immunoglobulin G antibodies in blood to diagnose and manage antibody deficiency disorders, assess functional immune responses, and guide immunoglobulin replacement therapy decisions.
Primary Clinical Applications
Diagnosis of Antibody Deficiency Syndromes
IgG testing is essential for diagnosing primary immunodeficiency diseases (PIDD), including common variable immunodeficiency (CVID), X-linked agammaglobulinemia, and selective antibody deficiency 1.
Hypogammaglobulinemia requiring treatment is defined by IgG levels <400-500 mg/dL combined with recurrent infections (at least 3 events per year) 2.
For patients on B-cell depleting therapies like rituximab, the threshold may be raised to 650 mg/dL due to iatrogenic immune suppression 2.
Assessment of Functional Antibody Responses
Measurement of baseline IgG levels should be followed by functional antibody testing, particularly pneumococcal antibody responses to the 23-valent polysaccharide vaccine, to distinguish true antibody deficiency from isolated low IgG levels 1.
Post-vaccination antibody titers are measured 4-8 weeks after immunization, with protective threshold defined as >1.3 μg/mL for more than 70% of pneumococcal serotypes 1.
Functional antibody assessment using opsonophagocytic assays provides more clinically meaningful information than simple quantitative antibody measurements, as it measures actual killing of organisms rather than just antibody concentration 1.
Guiding Immunoglobulin Replacement Therapy
IgG levels determine eligibility for intravenous immunoglobulin (IVIG) or subcutaneous immunoglobulin (SCIG) replacement therapy in patients with documented antibody deficiency and recurrent infections 2.
Target trough IgG levels during replacement therapy are 600-800 mg/dL, with monitoring required every 6-12 months to adjust dosing 2.
Serial IgG measurements help determine if hypogammaglobulinemia is transient or permanent, guiding decisions about continuing or discontinuing therapy 2.
Secondary Clinical Applications
Detection of B-Cell Malignancies and Paraproteinemias
Polyclonal elevation of IgG commonly occurs in bronchiectasis and chronic infections, reflecting ongoing inflammation 1.
Serum protein electrophoresis distinguishes polyclonal from monoclonal IgG elevations, identifying conditions like multiple myeloma, Waldenström's macroglobulinemia, chronic lymphocytic leukemia, and monoclonal gammopathy of uncertain significance (MGUS) 1.
Patients with B-cell lymphoproliferative disorders frequently develop secondary antibody deficiency requiring IgG monitoring and potential replacement therapy 2.
Monitoring Immune Recovery
For transient hypogammaglobulinemia, IgG levels are monitored every 3-6 months to assess recovery of endogenous antibody production 2.
Rising trough IgG levels while maintaining constant replacement doses indicate recovery of the patient's own antibody production 2.
Concurrent monitoring of IgA and IgM levels provides additional evidence of immune system recovery 2.
Important Clinical Caveats
Interpretation Pitfalls
IgG levels alone do not define immunodeficiency—clinical correlation with infection history and functional antibody responses is mandatory 1.
Marginally low IgG levels (near the lower limit of normal) require functional antibody testing before diagnosing true antibody deficiency 1.
During active infections, IgG catabolism accelerates significantly, shortening half-life from 18-23 days to 1-10 days, which affects interpretation of levels and replacement dosing 2.
Testing Strategy
Complete diagnostic evaluation should include: IgG quantification, IgA and IgM levels, lymphocyte subset enumeration (CD19, CD4, CD8, memory B cells), and pneumococcal vaccine challenge testing 2.
Document infection patterns before initiating replacement therapy: culture-proven bacterial infections, hospitalizations for infections, or failure of antibiotic therapy 2.
Consider antibiotic prophylaxis as an alternative to immunoglobulin replacement in borderline cases 2.
Specialized Applications
MOG-IgG testing uses cell-based assays to detect autoantibodies in MOG-associated encephalomyelitis, distinct from standard IgG quantification 1.
IgG subclass testing (IgG1-4) may be indicated when total IgG is normal but recurrent sinopulmonary infections suggest selective subclass deficiency 2, 3.
Post-transplant monitoring: IgG <400 mg/dL within 100 days of hematopoietic stem cell transplant indicates need for prophylactic IVIG 2.