What is being tested?

This test measures the amount of immunoglobulins A, G, and M in the blood and, in certain circumstances, in cerebrospinal fluid (CSF) . There are numerous conditions and diseases that can cause increased or decreased production of immunoglobulins (Igs).

Immunoglobulins play a key role in the body's immune system. They are proteins produced by specific immune cells (plasma cells and B-cells) in response to bacteria, viruses, and other microorganisms as well as substances that are recognized as "non-self" and harmful antigens. The first time a person is infected or otherwise exposed to a foreign substance (antigen), their immune system recognises the microorganism or substance as "non-self" and stimulates cells to produce specific immunoglobulin(s) or antibodies that can bind to and neutralise the threat. With subsequent exposures, the immune system "remembers" the antigen that was encountered, which allows for the rapid production of more antibodies and helps prevent re-infection.

There are five classes of immunoglobulins and several subclasses. Each class represents a group of antibodies and has a slightly different role. Classes of immunoglobulins include:

• Immunoglobulin G (IgG) – About 70-80% of the immunoglobulin in the blood is IgG. IgG antibodies form the basis of long-term protection against microorganisms. Specific IgG antibodies are produced during an initial infection or exposure, rising a few weeks after it begins, then decreasing and stabilising. The body retains a catalogue of IgG antibodies that can be rapidly reproduced whenever exposed to the same antigen. In those with a normal immune system, sufficient IgG is produced to prevent re-infection. Vaccinations use this process to prevent initial infections and add to the catalogue of IgG antibodies, by exposing a person to a weakened, live microorganism or to an antigen that stimulates recognition of the microorganism. IgG is the only immunoglobulin that can pass through the placenta. The mother's IgG antibodies provide protection to the fetus during pregnancy and to the baby during its first few months of life. There are four subclasses of IgG: IgG1, IgG2, IgG3, and IgG4. Measurement of these subclasses is very rarely useful. Having  a slightly low level of one subclass when the total IgG is normal is not suggestive of immune deficiency.
• Immunoglobulin A (IgA) – IgA comprises about 15% of the total serum immunoglobulins but is also found in saliva, tears, respiratory and gastric secretions, and breast milk. IgA provides protection against infection in areas of the body such as the respiratory tract and the gastrointestinal tract. When passed from mother to baby during breast-feeding, it helps protect the infant's gastrointestinal tract. Significant amounts of IgA are not present until after 6 months of age. IgA levels rise with age. There are two IgA subclasses: IgA1 and IgA2 though there is no indication for their measurement.
• Immunoglobulin M (IgM) – IgM antibodies are produced as a body's first response to a new infection, providing short-term protection. They increase for several weeks and then decline as IgG production begins. IgM can be produced by a fetus but, due to the size of the IgM molecule, it does not pass through the placenta. IgM antibodies in a newborn can indicate an infection that began during pregnancy.
• Immunoglobulin D (IgD) – the role of IgD is not well defined and IgD is not routinely measured.
• Immunoglobulin E (IgE) – IgE is associated with allergies, allergic diseases, and with parasitic infections. It is almost always measured as part of an allergy testing blood panel, but typically is not included as part of a quantitative immunoglobulins test.

Quantitative immunoglobulin tests measure the total amount of each primary immunoglobulin class, IgA, IgM, and IgG, without distinguishing between subclasses. Separate testing can be performed to measure immunoglobulin subclasses and/or to detect and measure specific antibodies.

A variety of conditions can cause an increase (hypergammaglobulinaemia) or decrease (hypogammaglobulinaemia) in the production of immunoglobulins. Some cause an excess or deficiency of all classes of Igs while others affect only one class. Some of the conditions are passed from one generation to the next (inherited) and others are acquired.

How is it used?

A quantitative immunoglobulins (Igs) test is used to detect abnormal levels of the three major classes of Igs (IgG, IgA, and IgM) in blood and sometimes in cerebrospinal fluid (CSF) or saliva. It is used to help diagnose various conditions and diseases that affect the levels of one or more of these Ig classes. Some conditions cause excess levels while others cause deficiencies; still others cause a combination of increased and decreased levels.

In general, immunoglobulin disorders can be classified as:

Immunoglobulin excess

• Resulting from many different immune (plasma) cells (polyclonal)
• Resulting from clones of one plasma cell (monoclonal)

Immunoglobulin deficiency

• Secondary (acquired)—the most common causes and are a result of some underlying condition
• Primary (inherited)—rare disorders in which the body is not able to produce one or more class of immunoglobulin
  Immunoglobulin testing may be ordered along with other tests, such as a serum and/or urine protein electrophoresis, to help diagnose and monitor conditions associated with abnormal or excessive immunoglobulin production. If an excessive amount of one of the immunoglobulin types is present, further testing by immunofixation can be done to determine if the immunoglobulin comes from clones of an abnormal plasma cell (monoclonal gammopathy). Such monoclonal gammopathies are seen with multiple myeloma, a malignancy of plasma cells. Additionally, free light chain testing may be performed.

Sometimes an IgM level is used to detect an infection acquired by a newborn before birth (congenital).

When is it requested?

A quantitative immunoglobulins blood test is ordered when a person has symptoms of an immunoglobulin deficiency such as recurrent infections, especially of the respiratory tract (sinus, lungs, and ears) or gastrointestinal tract, and/or chronic diarrhoea.

Immunoglobulins may also be ordered when a person has signs of chronic inflammation or chronic infection and when a doctor suspects excess or abnormal immunoglobulin production. The test may be ordered periodically to monitor the course of a person's condition. An infant may sometimes be tested when a doctor suspects that an infection occurred during pregnancy.

This test may also be performed on cerebrospinal fluid (CSF) whenever a doctor suspects that a condition affecting the central nervous system may be associated with excess immunoglobulin production.

What does the result mean?

The results of the tests for IgG, IgA, and IgM levels are usually evaluated together. Abnormal test results typically indicate that there is something affecting the immune system and suggest the need for further testing. This test is not specifically diagnostic but can be a strong indicator of a disease or condition. There are a number of conditions that are associated with increased and decreased immunoglobulins.

High levels

Increased polyclonal immunoglobulins may be seen with cirrhosis, infections, inflammatory disorders, and some tumours. Monoclonal immunoglobulins are seen in haematologic tumours that involve lymphocytes or plasma cells: lymphoma, Waldenström's macroglobulinaemia, chronic lymphocytic leukaemia and multiple myeloma. In these disorders, there is typically a marked increase in one class of immunoglobulin and a decrease in the other two classes. Although patients may have an increase in total immunoglobulins, they are actually immunocompromised because most of the immunolglobulin is abnormal and does not contribute to the immune response.

The following table shows some examples of conditions that may cause increased immunoglobulins:

Low levels
Acquired deficiencies, those that are the result of some underlying condition (secondary), may be seen with diseases that cause a general loss of protein, with cancers such as lymphoma, and with severe burns. Deficiencies may also be due to drugs such as immunosuppressants, corticosteroids, phenytoin, and carbamazepine or due to toxins. Inherited deficiencies are rare and may affect the production of all immunoglobulins, a single class, or one or more subclasses.

The most common causes of decreased immunoglobulins are secondary conditions that either affect the body's ability to produce immunoglobulins or increase the loss of protein from the body. The table below lists some of these common causes:

In CSF, immunoglobulins normally are present in very low concentrations. Increases may be seen, for example, with central nervous system infections and inflammatory conditions.

Is there anything else I should know?

Inherited immune deficiencies are rare and are often referred to as primary immunodeficiencies. (For more on this, see the links under the Related information tab). Some of these disorders include agammaglobulinaemia, common variable immunodeficiency (CVID), x-linked agammaglobulinaemia, ataxia telangiectasia, Wiskott-Aldrich syndrome, hyper-IgM syndrome, and severe combined immunodeficiency (SCID).

Infants with otherwise normal immune systems may have temporarily decreased IgG levels when production is delayed. Protection from infections is lost as concentrations of the mother's IgG in the baby's blood decrease over several months. The level of IgG remains at low concentrations until the baby's IgM and IgG production ramps up. This creates a period of time during which the baby is at an increased risk for recurrent infections.

Infants who are breast-fed acquire IgA from breast milk. The IgA in breast milk can be protective against infections, particularly in the time between the decrease of mother's antibodies and the production of the baby's own antibodies.

Those with conditions that cause decreased immunoglobulin levels often do not have a strong immune response to vaccinations; they may not produce a sufficient level of antibody to ensure protection and may not be able to receive live vaccines, such as those for polio or measles.

Many laboratory tests measure antibodies in the blood. Those with immunoglobulin deficiencies may have false-negative results on these types of tests. For example, one test for coeliac disease detects the IgA type of anti-tissue transglutaminase antibody (anti-tTG). If a person has a deficiency in IgA, then results of this test may be negative when the person, in fact, has celiac disease. If this is suspected to be the case, then a quantitative test for IgA may be performed.

Rarely those with IgA deficiency may develop anti-IgA antibodies. When those with anti-IgA are given blood component transfusions that contain IgA (such as plasma or immunoglobulin treatments), they may experience a severe anaphylactic transfusion reaction.

Common questions

• Should everyone have an immunoglobulins test?

A quantitative immunoglobulins test is not considered a routine or a general screening test. It is typically only ordered if your doctor suspects that you have an immunoglobulin deficiency or excess amount. Most people will never need to have one done.

• Is there something I can do to alter my immunoglobulins?

In most cases, immunoglobulins do not respond to lifestyle changes. If you are taking a drug that is decreasing one or more of your immunoglobulins, then you and your doctor may decide to alter your medications. It is very important, however, NOT to discontinue or change your medication dosage without consulting with your physician. Increased amounts may be temporarily reduced by plasmapheresis if medically indicated.

Infants gradually lose protection from infections as the levels of IgG they receive through the placenta from their mothers decrease after birth. Greater protection can be provided for babies through breast-feeding since breast milk contains IgA, which protects against infections. In the first two years of life, the baby’s ability to produce their own immunoglobulin matures.

• Are there symptoms associated with decreased immunoglobulins?

Not specific ones. Unexplained recurrent infections, multiple infections, or opportunistic infections, with or without chronic diarrhoea, may indicate a need to check a person's immune status. A positive family history of an immunodeficiency may also require follow up. A thorough physical examination and a careful medical history can be critical to a diagnosis.

More information

RCPA Manual: Immunoglobulins