Test Catalog

Test ID: IGGS    
IgG Subclasses, Serum

Useful For Suggests clinical disorders or settings where the test may be helpful

Second-order testing for evaluation of patients with clinical signs and symptoms of humoral immunodeficiency or combined immunodeficiency (cellular and humoral)

Testing Algorithm Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

Testing includes total immunoglobulin G (IgG) as well as the 4 subclasses of IgG.


See Celiac Disease Diagnostic Testing Algorithm in Special Instructions

Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

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 Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.


0-<5 months: 100-334 mg/dL

5-<9 months: 164-588 mg/dL

9-<15 months: 246-904 mg/dL

15-<24 months: 313-1,170 mg/dL

2-<4 years: 295-1,156 mg/dL

4-<7 years: 386-1,470 mg/dL

7-<10 years: 462-1,682 mg/dL

10-<13 years: 503-1,719 mg/dL

13-<16 years: 509-1,580 mg/dL

16-<18 years: 487-1,327 mg/dL

> or =18 years: 767-1,590 mg/dL



0-<5 months: 56-215 mg/dL  

5-<9 months: 102-369 mg/dL

9-<15 months: 160-562 mg/dL

15-<24 months: 209-724 mg/dL

2-<4 years: 158-721 mg/dL

4-<7 years: 209-902 mg/dL

7-<10 years: 253-1,019 mg/dL

10-<13 years: 280-1,030 mg/dL

13-<16 years: 289-934 mg/dL

16-<18 years: 283-772 mg/dL

> or =18 years: 341-894 mg/dL



0-<5 months: < or =82 mg/dL

5-<9 months: < or =89 mg/dL

9-<15 months: 24-98 mg/dL

15-<24 months: 35-105 mg/dL

2-<4 years: 39-176 mg/dL

4-<7 years: 44-316 mg/dL

7-<10 years: 54-435 mg/dL

10-<13 years: 66-502 mg/dL

13-<16 years: 82-516 mg/dL

16-<18 years: 98-486 mg/dL

> or =18 years: 171-632 mg/dL



0-<5 months: 7.6-82.3 mg/dL

5-<9 months: 11.9-74.0 mg/dL

9-<15 months: 17.3-63.7 mg/dL

15-<24 months: 21.9-55.0 mg/dL

2-<4 years: 17.0-84.7 mg/dL

4-<7 years: 10.8-94.9 mg/dL

7-<10 years: 8.5-102.6 mg/dL

10-<13 years: 11.5-105.3 mg/dL

13-<16 years: 20.0-103.2 mg/dL

16-<18 years: 31.3-97.6 mg/dL

> or =18 years: 18.4-106.0 mg/dL



0-<5 months: < or =19.8 mg/dL

5-<9 months: < or =20.8 mg/dL

9-<15 months: < or =22.0 mg/dL

15-<24 months: < or =23.0 mg/dL

2-<4 years: 0.4-49.1 mg/dL

4-<7 years: 0.8-81.9 mg/dL

7-<10 years: 1.0-108.7 mg/dL

10-<13 years: 1.0-121.9 mg/dL

13-<16 years: 0.7-121.7 mg/dL

16-<18 years: 0.3-111.0 mg/dL

> or =18 years: 2.4-121.0 mg/dL

Interpretation Provides information to assist in interpretation of the test results

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.


Elevated levels of IgG4 are consistent with, but not diagnostic of, IgG4-related disease.


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.

Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

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.

Clinical Reference Recommendations for in-depth reading of a clinical nature

Umetsu DT, Ambrosino DM, Quinti I, et al: Recurrent sinopulmonary infection and impaired antibody response to bacterial capsular polysaccharide antigen in children with selective IgG-subclass deficiency. N Engl J Med 1985;313:1247-1251

Special Instructions Library of PDFs including pertinent information and forms related to the test