Reference Range

Immunoglobulins are glycoprotein molecules that are produced by plasma cells in response to an immunogen. Indications for serum immunoglobulin testing include diagnosis and monitoring of monoclonal gammopathies and immune deficiencies.

Reference ranges of immunoglobulins may vary based on sex and factors such as alcohol use, smoking status, and chronic conditions (eg, diabetes/metabolic syndrome) (see Considerations).

Normal findings

Age and methods impact results.^[1]

Immunoglobulin G (IgG) (mg/dL)^[1]

Adults: 565-1765
Children: 250-1600

IgA (mg/dL)^[1]

Adults: 85-385
Children: 1-350

IgM (mg/dL)^[1]

Adults: 55-375
Children: 20-200

IgD and IgE^[1]

Minimal

Interpretation

Conditions associated with a polyclonal or oligoclonal increase in serum immunoglobulin levels include the following:

Acute and chronic infections
Intrauterine or perinatal infection in neonates (eg, syphilis, toxoplasmosis, rubella, cytomegalovirus)
Autoimmune disorders (eg, rheumatoid arthritis, systemic lupus erythematosus, scleroderma)
Hepatic disease (hepatitis, cirrhosis)
Chronic inflammation

Conditions associated with a monoclonal increase in serum immunoglobulin levels include the following:

Multiple myeloma
Chronic lymphocytic leukemia (CLL)
Monoclonal gammopathy of undetermined significance (MGUS)
Primary systemic amyloidosis
Lymphoma
Waldenstrom macroglobulinemia (IgM)

Conditions associated with a decrease in serum immunoglobulin levels include the following:

Abnormal immunoglobulin production: Drugs (eg, phenytoin, carbamazepine, immunosuppressants), diabetes mellitus, chronic renal failure, premature birth (transient)
Abnormal protein loss: Nephrotic syndrome, burns, protein-losing enteropathy
Inherited immune deficiencies (rare): Agammaglobulinemia, common variable immunodeficiency (CVID), X-linked agammaglobulinemia, ataxia telangiectasia,Wiskott-Aldrich syndrome (decreased IgM level), severe combined immunodeficiency (SCID)

Collection and Panels

Specifics for collection and panels are as follows:

Specimen type: Blood serum
Container: Vacutainer, gold top or gel-barrier tube
Collection method: Venipuncture
Specimen volume: 1 mL
Methodology: Immunologic
Other instructions: Serum protein electrophoresis is required to distinguish between polyclonal and monoclonal immunoglobulin increases
Limitation: The test is not suitable for the measurement of samples containing rheumatoid factor, paraproteins, circulating immune complexes, lipemic or hemolyzed samples owing to unpredictable degree of light scatter

Related tests: Serum protein electrophoresis, total protein, serum complement, serum immunoglobulin free light chains

Serum vacuette 6-mL tube.

Description

Immunoglobulins are glycoprotein molecules that are produced by plasma cells in response to an immunogen. The immunoglobulins derive their name as they migrate with globular proteins when antibody-containing serum is placed in an electrical field.

The immunoglobulins are divided into 5 different classes, based on differences in the amino acid sequences in the constant region of the heavy chains. All immunoglobulins within a given class have very similar heavy chain constant regions. These differences can be detected by sequence studies or more commonly by serological means (ie, via antibodies directed to these differences), as follows:

IgG - Gamma heavy chains
IgM - Mu heavy chains
IgA - Alpha heavy chains
IgD - Delta heavy chains
IgE - Epsilon heavy chains

The classes of immunoglobulins can be divided into subclasses based on small differences in the amino acid sequences in the constant region of the heavy chains. All immunoglobulins within a subclass have very similar heavy chain constant region amino acid sequences. Again, these differences are most commonly detected with serological means.

IgG subclasses are as follows:

IgG1 - Gamma 1 heavy chains
IgG2 - Gamma 2 heavy chains
IgG3 - Gamma 3 heavy chains
IgG4 - Gamma 4 heavy chains

IgA subclasses are as follows:

IgA1 - Alpha 1 heavy chains
IgA2 - Alpha 2 heavy chains

Immunoglobulins can also be classified by their type of light chain. Light chain types are based on differences in the amino acid sequence in the constant region of the light chain. These differences are detected with serological means. The light chains can be further divided into subtypes based on differences in the amino acid sequences in the constant region of the light chain, as follows:

Kappa light chains
Lambda light chains (Lambda 1, Lambda 2, Lambda 3, Lambda 4)

Quantitative immunoglobulins testing is used to measure levels of the 3 major immunoglobulin classes—IgG, IgA, and IgM—which make up 80%, 15%, and 5%, respectively, of normal serum immunoglobulins.

Indications/Applications

Indications for serum immunoglobulin testing include diagnosis and monitoring of monoclonal gammopathies and immune deficiencies.

Considerations

Median IgA values may be 20% higher in males, whereas median IgM values may be 30% higher in females. Sex differences in immunoglobulin concentrations, speciﬁcally high IgM levels in females, have been attributed to hormonal effects on B lymphocytes.^{[2, 3]}

Alcohol consumption is associated with increased serum IgA levels, being higher in heavy drinkers than in light-to-moderate drinkers and abstainers. IgA increase in heavy drinkers is selective, not affecting IgM or IgG. In fact, serum IgG concentrations tend to be lower in moderate alcohol consumers than in abstainers.^[4]

Smoking is associated with decrease in IgG levels.^[4]Significant immunomodulatory effects occur with both smoking and alcohol consumption.^[5]

Diabetes mellitus/metabolic syndrome is associated with increased IgA concentrations. It is associated with hyperglycemia, triglyceridemia, and abdominal obesity. These 3 factors selectively affect only the IgA class, with the exception of an IgM increase in individuals with dyslipidemia. There is a correlation between increase in IgA and interleukin 6 (IL-6), which are both elevated in chronic inflammatory disorders.