Quantitative Immunoglobulins

A test for quantitative immunoglobulins (Igs) is used to detect an excess or deficiency in the three major classes of immunoglobulins (IgG, IgA, and IgM). It gives important information about the health of an individual's immune system and is used to help diagnose various conditions and diseases that affect the levels of one or more of these Ig classes.

In general, immunoglobulin disorders can be classified as:

• Immunoglobulin excess
  • Polyclonal: Excess is the sum of immunoglobulins from many different immune (plasma) cells
  • Monoclonal: Excess immunoglobulins are from the clones of one plasma cell


• Immunoglobulin deficiency
  • Secondary (acquired)—the most common are caused by an underlying condition or contributing factor
  • Primary (inherited)—rare disorders in which the body is not able to produce one or more classes of immunoglobulins

This test may be requested along with others, such as a serum and/or urine protein electrophoresis, to help diagnose and monitor conditions associated with abnormal or excessive immunoglobulin production. When this is the case, a urine sample may be collected in addition to blood. Occasionally a paraprotein can be present but not picked up by quantitative immunoglobulin testing, due to interference in the assays by high levels of proteins. When myeloma is suspected a serum protein electrophoresis should always be carried out at the same time to make sure a paraprotein isn’t missed.

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). Monoclonal gammopathies are seen with multiple myeloma, a malignancy of plasma cells. Serum free light chain testing may also be performed.Light chains are a fragment of immunoglobulins and are sometimes detected “free” in the blood without a rise in whole immunoglobulin molecules, this is known as free light chain disease.

This test is requested when a person has symptoms of an immunoglobulin deficiency such as recurrent infections, especially of the respiratory tract (sinus, lungs) or gastrointestinal tract (stomach, intestines), and/or chronic diarrhoea. It may be part of the investigation of anaeamia, raised white cell count, bone pain or fractures that occur with minimal trauma (pathological fractures).

Immunoglobulins testing may also be requested when a person has signs of chronic inflammation or chronic infection and when a healthcare professional suspects excess or abnormal immunoglobulin production. The test may be requested periodically to monitor the course of a person's condition.

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

The results of the tests for IgG, IgA, and IgM are usually evaluated together. Abnormal test results typically indicate that there is something affecting the immune system and suggest the need for further testing. Quantitative immunoglobulins testing is not 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 a variety of conditions such as chronic infection or inflammatory disease. Monoclonal immunoglobulins may be present in small quantities and are then call an MGUS (monoclonal gammopathy of uncertain significance). Most patients with an MGUS just need observation, with a low proportion going on to develop myeloma. Monoclonal immunoglobulins are also seen, but usually at high levels, in blood cell tumours that involve lymphocytes or plasma cells. In these disorders, there is typically a marked increase in one class of immunoglobulin and a decrease in the other two classes. Although affected people may have an increase in total immunoglobulins, they may be immunocompromised because most of the immunolglobulins produced are abnormal and do not contribute to the immune response.

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

Low levels

The most common causes of decreased immunoglobulins are acquired underlying (secondary) conditions that either affect the body's ability to produce immunoglobulins or that increase the loss of protein from the body. Deficiencies may also be due to drugs such as immunosuppressants, corticosteroids, phenytoin, and carbamazepine or due to toxins.

The table below lists some of the common causes of low levels:

Inherited immune deficiencies are rare and are often referred to as primary immunodeficiencies. (For more on this, see the links on the Related Pages tab). They may affect the production of all immunoglobulins, a single class, or one or more subclasses. Some of these disorders include common variable immunodeficiency (CVID), x-linked agammaglobulinemia, ataxia telangiectasia, Wiskott-Aldrich syndrome, hyper-IgM syndrome, and severe combined immunodeficiency (SCID).

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

Decreases in salivary IgA may be seen in those with recurrent respiratory infections.

Sometimes an IgM test is used to determine whether a newborn acquired an infection before or after birth (congenital). IgM may be produced by a baby, just like an adult, in response to infection. Due to the size of IgM antibodies, they cannot pass through the placenta from mother to baby during pregnancy. Thus, any IgM antibodies present in a newborn's blood are not from the mother but were produced by the baby. Usually looking at both the babies and the mother’s blood tests for IgG and IgM antibodies allows doctors a better idea of when infection occurred.

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 breastfed 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 class 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 coeliac disease. If this is suspected to be the case, then a quantitative test for IgA may be performed.

If IgG concentrations are decreased, or a deficiency in a subclass is suspected, then testing may be performed to detect and further define the deficiency. Subclass deficiencies can be present even when an immunoglobulin class concentration, such as IgG, is normal. These are usually subtle abnormalities, and as such they are rarely the cause of major clinical infection and subclass testing is now rarely performed.

Some people with IgA deficiencies 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 rarely experience a severe anaphylactic transfusion reaction. The current advice is only to test IgA deficient patients for IgA antibodies if they have previously reacted to a blood product. The majority of patients do not develop IgA antibodies and even in those with an anti-IgA antibody most do not react to blood products.

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