What is being tested?
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 recognized 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 recognizes the microorganism or substance as “non-self” and stimulates plasma cells to produce specific immunoglobulin(s), also called antibodies, that can bind to and neutralize the threat. With subsequent exposures, the immune system “remembers” the antigen that was encountered, which allows for the rapid production of more antibodies 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 stabilizing. The body retains a catalog 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 initial infections and add to the catalog 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.
- Immunoglobulin A (IgA) – IgA comprises about 15% of the total immunoglobulins in the blood but is also found in saliva, tears, respiratory and gastric 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) – the role of IgD is not completely understood 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.
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 test used?
A test for 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—an Ig excess in any or all immunoglobulin classes from many different immune (plasma) cells
- Monoclonal—the excess immunoglobulins are from the clones of one plasma cell
- Immunoglobulin deficiency
- Secondary (acquired)—the most common Ig deficiencies are caused by an underlying condition or contributing factor
- Primary (inherited)—these are rare disorders in which the body is not able to produce one or more classes of immunoglobulins
This test may be ordered 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.
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.
When is it ordered?
This test is ordered when a person has symptoms of an immunoglobulin deficiency such as recurrent infections, especially of the respiratory tract (sinus, lungs) or digestive system (stomach, intestines), and/or chronic diarrhea.
Immunoglobulins testing may also be ordered when a person has signs of chronic inflammation or chronic infection and when a health care practitioner suspects excess or abnormal immunoglobulin production. The test may be ordered periodically to monitor the course of a person’s condition.
This test may also be performed on cerebrospinal fluid (CSF) whenever a health practitioner suspects that a condition affecting the central nervous system may be associated with excess immunoglobulin production.
What does the test 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. 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.
Monoclonal immunoglobulins are seen in blood cell tumors 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 are actually immunocompromised because most of the immunoglobulins 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)||
|Monoclonal increase in one class with or without decrease in other two classes||
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||
Inherited immune deficiencies are rare and are often referred to as primary immunodeficiencies. They may affect the production of all immunoglobulins, a single class, or one or more subclasses. Some of these disorders include agammaglobulinemia, 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?
People 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 celiac 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 celiac disease. If this is suspected to be the case, then a quantitative test for IgA may be performed.
If IgG or IgA concentrations are decreased, or a deficiency in one of their subclasses is suspected, then subclass 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.
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 experience a severe anaphylactic transfusion reaction.
My newborn had an immunoglobulin test. Why?
Sometimes an IgM test is used to determine whether a newborn acquired an infection before birth (congenital). IgM may be produced by a developing baby (fetus) 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. This indicates that an infection began during pregnancy.
What is transient hypogammaglobulinemia of infancy (THI)?
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.
However, 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.
Is there something I can do to alter my immunoglobulin levels?
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 practitioner 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.
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 diarrhea, 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 practitioner 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. 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.