Immunoglobulins (IgG, IgA, IgM, IgE)
Last updated: October 9, 2014
Description: Immunoglobulins are serum antibodies produced by plasma cells and are the major component of the humoral immune response. Measurement of serum immunoglobulins of different isotypes (i.e., IgG, IgA, IgM, IgE) may be useful in a variety of immunodeficiency, infectious, allergic, and lymphoproliferative diseases.
Method: Serum immunoglobulins are currently measured by specific immunologic methods such as ELISA.
Normal Values: Concentrations may vary slightly depending on the laboratory and the particular methods used, but, in general, normal values for serum immunoglobulins in healthy adults are as follows: IgG, 550 to 1,900 mg/dL; IgM, 50 to 150 mg/dL; and IgA, 60 to 350 mg/dL. IgE is usually present in far smaller amounts.
Serum immunoglobulin concentrations depend on a number of developmental, genetic, and environmental factors, among which the most important is age. IgG synthesized by the mother crosses the placenta in increasing amounts beginning at approximately 3 months of fetal development. At birth, this maternal contribution to the newborn’s IgG stops, and total IgG levels slowly decrease until the contribution from the newborn increases at approximately 4 to 6 months of age. Levels of immunoglobulins increase throughout childhood, generally reaching adult concentrations by age 12.
Abnormal Values: Values vary according to clinical situation, therapy, and isotype.
—IgE: Most methods currently used do not ascribe any significance to very low concentrations of IgE (i.e., normal persons may have undetectable serum concentrations of IgE). Elevated serum IgE concentrations correlate with a proclivity to allergic conditions such as allergic rhinitis, asthma, atopic skin disease, anaphylactic shock, and some parasitic infections. However, determination of IgE specific for particular antigens is of greater significance in evaluating patients with allergic diseases than measurements of total IgE. Antigen-specific IgE may be determined by in vivo tests such as the cutaneous scratch tests using particular allergens or by in vitro methods such as the radioallergosorbent test.
—IgM: IgM usually circulates in a large molecular weight pentamer and remains almost entirely within the vasculature and does not cross the placenta. It is the earliest immunoglobulin synthesized in response to anti-genic challenge. Decreased IgM levels may be seen in humoral immunodeficiencies such as common variable immunodeficiency or in conditions of excess protein loss such as nephrotic syndrome. Polyclonal increases in IgM may be seen during the course of various infections or autoimmune disorders in which there is polyclonal stimulation of the immune response. Monoclonal elevations in IgM are seen in neoplastic proliferations of B cells, e.g., Waldenström macroglobulinemia. Because of their large size, IgM aggregates are more likely to affect plasma viscosity and cause clinical symptoms than are other immunoglobulin isotypes. Clinically important IgM antibodies are directed against RF and the ABO blood groups.
—IgA: Serum concentrations of IgA reflect the amounts of two isotypes, IgA1 and IgA2. Although these are present in approximately equal amounts in serum, IgA1 is the predominant IgA isotype secreted onto mucosal surfaces.This secreted form is an important part of the immune response to pathogens present on mucosal surfaces. Serum IgA levels, therefore, may not reflect the functional status of IgA-mediated responses. Indeed, serum concentrations of IgA below the lower limits of normal, the most commonly observed humoral immunodeficiency, are found in one in 700 persons. Although the vast majority of these patients are asymptomatic, decreased serum levels of IgA may also be seen in immunodeficient patients, e.g., those with common variable immunodeficiency.
—IgG: IgG is present in approximately equal amounts in the intravascular and extravascular compartments and comprises nearly 80% of the circulating immunoglobulin. It is the most important immunoglobulin isotype in secondary (anamnestic) immune responses. Total serum IgG represents the sum of the four IgG subclasses (IgG1, IgG2, IgG3, and IgG4), which are numbered in descending order of their concentration in normal serum. Thus, isolated deficiencies of IgG1 typically are evidenced as a decrease in total IgG [as well as decreased gamma fraction of serum protein electrophoresis (SPEP)]. By contrast, deficiencies of IgG3 or IgG4 may be masked within a normal total IgG concentration.
Confounding Factors: Leaving samples at room temperature for hours may result in lower immunoglobulin levels. Radiation therapy, chemotherapy, and high-dose corticosteroids may also lower serum immunoglobulin levels.
Indications: Quantitative serum immunoglobulin (IgG, IgA, IgM) determinations are appropriate for initial evaluation of a patient with suspected humoral (antibody) immunodeficiency. If these are normal but there is a very high clinical suspicion of humoral immunodeficiency, it may be appropriate to obtain IgG subclasses or antigen-specific antibody titers (e.g., serum titers of antipneumococcal antibody in patients who have been appropriately vaccinated). Testing is also indicated in the diagnosis of some paraproteinemias such as multiple myeloma and Waldenström macroglobulinemia.