When you have recurrent infections and/or chronic diarrhoea; when your healthcare professional suspects an immunoglobulin deficiency; periodically to monitor a condition that affects immunoglobulin levels that may be genetic or acquired (HIV/AIDS, multiple myeloma), as part of the investigation of anaemia and bone pain with raised ESR (multiple myeloma, Waldenstrom’s macroglobulinaemia).
Immunoglobulins play a key role in the body's immune system. They are proteins produced by specific immune cells called plasma cells in response to bacteria, viruses, and other microorganisms as well as exposures to other substances that are recognised by the body as "non-self" harmful antigens. This test measures the amount of immunoglobulins A, G, and M (IgA, IgG, IgM) in the blood and, in certain circumstances, in cerebrospinal fluid (CSF) or saliva.
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 B-cells (a type of lymphocyte or white blood cell) to produce specific immunoglobulin(s), also called 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 by plasma cells (long lived subset of B-cells that are like antibody factories in the bone marrow) and, in the case of microorganisms, 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 M (IgM) – IgM antibodies are produced as a body's first response to a new infection or to a new "non-self" antigen, providing short-term protection. They increase for several weeks and then decline as IgG production begins.
- Immunoglobulin G (IgG) – About 70-80% of the immunoglobulins in the blood are IgG. Specific IgG antibodies are produced during an initial infection or other antigen 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. IgG antibodies form the basis of long-term protection against microorganisms. In those with a normal immune system, sufficient IgG is produced to prevent re-infection. Vaccinations use this process to prevent infections adding to the catalogue of IgG antibodies, by exposing a person to a killed or weakened, live microorganism or to an antigen that stimulates recognition of the microorganism. IgG is the only immunoglobulin that can pass through the placenta from the mother to the baby. The mother's IgG antibodies provide protection to the developing baby during pregnancy and then during its first few months of life after birth. There are four subclasses of IgG: IgG1, IgG2, IgG3, and IgG4.
- Immunoglobulin A (IgA) – IgA comprises about 15% of the total lung and stomach secretions, and breast milk. IgA provides protection against infection in mucosal areas of the body such as the respiratory tract (sinus and lungs) and the gastrointestinal tract (stomach and intestines). When passed from mother to baby during breast-feeding, it helps protect the infant's gastrointestinal tract. Significant amounts of IgA are not produced by a baby until after 6 months of age so any IgA present in a baby's blood before then is from the mother's milk. There are two IgA subclasses: IgA1 and IgA2.
- Immunoglobulin D (IgD) – This is not usually a secreted antibody, it is the first antibody produced as a receptor on B-cells (B-lymphocytes), it can be abnormally secreted in rare disorders (Hyper IgD Syndrome or HIDS).
- 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 because the levels are far too low to be detected by the same methods.
Quantitative immunoglobulins testing measures 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 (hypergammaglobulinemia) or decrease (hypogammaglobulinemia) in the production of immunoglobulins. Some cause an excess or deficiency of all classes of immunoglobulins 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 the sample collected for testing?
A blood sample is obtained by inserting a needle into a vein in the arm. When required, a sample of cerebrospinal fluid (CSF) is collected by a healthcare professional from the lower back using a procedure called a lumbar puncture or spinal tap. Saliva or other fluids are collected in a container provided by the laboratory.
Is any test preparation needed to ensure the quality of the sample?
No test preparation is needed.
How is it used?
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.
- Immunoglobulin excess
When is it requested?
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.
What does the test result mean?
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.
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:
Immunoglobulin Result Associated Conditions Polyclonal increase in any or all of the three classes (IgG, IgA and/or IgM)
- Infections, acute and chronic
- Autoimmune disorders (rheumatoid arthritis, systemic lupus erythematosus, scleroderma)
- Chronic inflammation, inflammatory disorders
- Hyperimmunisation reactions
- Wiskott-Aldrich syndrome
- In a newborn, infection during pregnancy (congenital—syphilis, toxoplasmosis, rubella, CMV)
Monoclonal increase in one class with or without decrease in other two classes
- Multiple myeloma
- Chronic lymphocytic leukaemia (CLL)
- MGUS (monoclonal gammopathy of undetermined significance)
- Waldenstrom's macroglobulinemia (IgM)
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:
Conditions/factors that affect immunoglobulin production Conditions that cause an abnormal loss of protein
- Nephrotic syndrome—kidney disease in which protein is lost in the urine
- Protein-losing enteropathy—any condition of the gastrointestinal tract that affects the digestion or absorption of protein
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.
Is there anything else I should know?
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.
Should everyone have an immunoglobulins test?
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 healthcare professional may decide to alter your medications. It is very important, however, NOT to discontinue or change your medication dosage without consulting with your healthcare provider. 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 breastfeeding since breast milk contains IgA, which protects against infections.
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.
In addition to the blood sample for this test, I was instructed to collect a urine sample. Why?
You may have been directed to give a urine sample to check for the presence of protein in your urine and/or to determine the amount and type of protein present in your urine. Your healthcare professional may suspect that, based on your medical history, signs and symptoms and/or other test results, you have a condition associated with abnormal or excessive immunoglobulin production or protein loss in your urine. In such cases, a quantitative immunoglobulin test is often performed along with tests such as serum and urine protein electrophoresis to help establish a diagnosis.
On This Site
Tests: Protein Electrophoresis, Immunofixation Electrophoresis, Total Protein, Autoantibodies, Complement, Serum Free Light Chains, Immunoglobulin Subclasses, Coeliac Disease Tests
Conditions: Multiple Myeloma, Allergies, Autoimmune Disorders, Leukaemia, Lymphoma, Liver Disease