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22605 IgG Subclasses (IGGS)

IgG Subclasses (IGGS)
Test Code: IGGMAYO
Synonyms/Keywords
​IgG (Immunoglobulin G) Subclasses, IgG Subclasses, IgG1, IgG2, IgG3, IgG4 (Immunoglobulins G1, G2, G3, G4), Immunoglobulin G (IgG), Subclasses, IgG (Immunoglobulin G)
Useful For
​A second-order test for evaluating patients with clinical signs and symptoms of humoral immunodeficiency or combined immunodeficiency (cellular and humoral)
Specimen Requirements
Specimen Type Preferred Container/Tube Acceptable Container/Tube Specimen Volume Specimen Minimum Volume
(allows for 1 repeat)
Pediatric Minimum Volume
(no repeat)
​Serum Red Top Tube (RTT)​ Serum Separator Tube (SST)​ 1 mL​ 0.5 mL​
Collection Processing Instructions

​Fasting preferred but not required

Specimen Stability Information
Specimen Type Temperature Time
Serum​ ​ ​ Refrigerated (preferred)​ 14 days​
Ambient ​ 14 days​
Frozen ​ 14 days​
Rejection Criteria
Gross lipemia
Interference

​Measurement of immunoglobulin G (IgG) subclass proteins is not a first-order test in patients suspected of having an immunodeficiency disease. Quantitation of IgG, immunoglobulin A, and immunoglobulin M levels, along with other first-order tests for immunodeficiency, should be performed first.

Elevations in serum IgG4 concentrations are not specific to IgG4-related disease; they are also found in disorders such as multicentric Castleman disease, allergic disorders, Churg-Strauss syndrome, sarcoidosis, and a large number of other conditions.

Performing Laboratory Information
Performing Location Day(s) Test Performed Analytical Time Methodology/Instrumentation
Mayo Clinic Laboratories
Monday through Friday​ 1-3 day​s
Nephelometry
Reference Lab
Test Information

The most abundant immunoglobulin in human serum is immunoglobulin G (IgG) (approximately 80% of the total). IgG protein is comprised of molecules of 4 subclasses designated IgG1 through IgG4. Each subclass contains molecules with a structurally unique gamma heavy chain. Of total IgG, approximately 65% is IgG1, 25% is IgG2, 6% is IgG3, and 4% is IgG4. Molecules of different IgG subclasses have somewhat different biologic properties (eg, complement fixing ability and binding to phagocytic cells), which are determined by structural differences in gamma heavy chains. Clinical interest in IgG subclasses concerns potential immunodeficiencies (eg, subclass deficiencies) and IgG4-related diseases (eg, IgG4 elevations). This assay is best for deficiency testing, and the IgG4 assay (IGGS4 / Immunoglobulin Subclass IgG4, Serum) is best for IgG4-related disease testing.

Diminished concentrations of IgG subclass proteins may occur in the context of hypogammaglobulinemia (eg, in common variable immunodeficiency where all immunoglobulin classes are generally affected) or deficiencies may be selective, usually involving IgG2. Deficiency of IgG1 usually occurs in patients with severe immunoglobulin deficiency involving other IgG subclasses. Deficiency of IgG2 is more heterogeneous and can occur as an isolated deficiency or in combination with deficiency of immunoglobulin A (IgA), or of IgA and other IgG subclasses. Most patients with IgG2 deficiency present with recurrent infections, usually sinusitis, otitis, or pulmonary infections. Children with deficiency of IgG2 often have deficient antibody responses to polysaccharide antigens including bacterial antigens associated with Haemophilus influenzae type B and Streptococcus pneumoniae. Isolated deficiencies of IgG3 or IgG4 occur rarely, and the clinical significance of these findings is not clear.

IgG subclass 4-related disease is a recently recognized syndrome of unknown etiology most often occurring in middle-aged and older men. Several organ systems can be involved and encompasses many previous and newly described diseases such as type 1 autoimmune pancreatitis; Mikulicz disease and sclerosing sialadenitis; inflammatory orbital pseudotumor; chronic sclerosing aortitis; Riedel thyroiditis, a subset of Hashimoto thyroiditis; IgG4-related interstitial pneumonitis; and IgG4-related tubulointerstitial nephritis. Each of these entities is characterized by tumor-like swelling of the involved organs with infiltrative, predominately IgG4-positive, plasma cells with accompanying "storiform" fibrosis. In addition, elevated serum concentrations of IgG4 are found in 60% to 70% of patients diagnosed with IgG4-related disease.

The diagnosis of IgG4-related disease requires a tissue biopsy of the affected organ demonstrating the aforementioned histological features. It is recommended that patients suspected of having an IgG4-related disease have their serum IgG4 level measured.

Testing for IgG subclass levels may be indicated in patients with clinical evidence of a possible immunodeficiency with hypogammaglobulinemic patients or normal concentrations of total serum IgG.

Reference Range Information
Interpretive report
Interpretation
​Diminished concentrations of all immunoglobulin G (IgG) subclasses are found in common variable immunodeficiency, combined immunodeficiency, ataxia telangiectasia, and other primary and acquired immunodeficiency diseases.  
 
A diminished concentration of IgG2 protein may be clinically significant in the context of recurrent sinopulmonary infection and may occur with or without concomitant immunoglobulin A deficiency.
 
Slightly diminished concentrations of 1 or more IgG subclass proteins are not uncommon, and usually have little clinical significance.
 
Conversely, some individuals with deficient specific antibody responses to polysaccharide antigens may have normal serum levels of IgG subclasses.
Outreach CPTs
CPT Modifier
(if needed)
Quantity Description Comments
82787​ 4​ IgG subclasses​
​82784 IgG​
Synonyms/Keywords
​IgG (Immunoglobulin G) Subclasses, IgG Subclasses, IgG1, IgG2, IgG3, IgG4 (Immunoglobulins G1, G2, G3, G4), Immunoglobulin G (IgG), Subclasses, IgG (Immunoglobulin G)
Ordering Applications
Ordering Application Description
​Centricity ​IgG Subclasses-Mayo
​Cerner ​IgG Subclasses (9259)
If the ordering application you are looking for is not listed, contact your local laboratory for assistance.
Specimen Requirements
Specimen Type Preferred Container/Tube Acceptable Container/Tube Specimen Volume Specimen Minimum Volume
(allows for 1 repeat)
Pediatric Minimum Volume
(no repeat)
​Serum Red Top Tube (RTT)​ Serum Separator Tube (SST)​ 1 mL​ 0.5 mL​
Collection Processing

​Fasting preferred but not required

Specimen Stability Information
Specimen Type Temperature Time
Serum​ ​ ​ Refrigerated (preferred)​ 14 days​
Ambient ​ 14 days​
Frozen ​ 14 days​
Rejection Criteria
Gross lipemia
Interference

​Measurement of immunoglobulin G (IgG) subclass proteins is not a first-order test in patients suspected of having an immunodeficiency disease. Quantitation of IgG, immunoglobulin A, and immunoglobulin M levels, along with other first-order tests for immunodeficiency, should be performed first.

Elevations in serum IgG4 concentrations are not specific to IgG4-related disease; they are also found in disorders such as multicentric Castleman disease, allergic disorders, Churg-Strauss syndrome, sarcoidosis, and a large number of other conditions.

Useful For
​A second-order test for evaluating patients with clinical signs and symptoms of humoral immunodeficiency or combined immunodeficiency (cellular and humoral)
Reference Range Information
Interpretive report
Interpretation
​Diminished concentrations of all immunoglobulin G (IgG) subclasses are found in common variable immunodeficiency, combined immunodeficiency, ataxia telangiectasia, and other primary and acquired immunodeficiency diseases.  
 
A diminished concentration of IgG2 protein may be clinically significant in the context of recurrent sinopulmonary infection and may occur with or without concomitant immunoglobulin A deficiency.
 
Slightly diminished concentrations of 1 or more IgG subclass proteins are not uncommon, and usually have little clinical significance.
 
Conversely, some individuals with deficient specific antibody responses to polysaccharide antigens may have normal serum levels of IgG subclasses.
For more information visit:
Performing Laboratory Information
Performing Location Day(s) Test Performed Analytical Time Methodology/Instrumentation
Mayo Clinic Laboratories
Monday through Friday​ 1-3 day​s
Nephelometry
Reference Lab
For billing questions, see Contacts
Outreach CPTs
CPT Modifier
(if needed)
Quantity Description Comments
82787​ 4​ IgG subclasses​
​82784 IgG​
For most current information refer to the Marshfield Laboratory online reference manual.