Summary

• Immunoglobulins are also known as antibodies.
• Your immune system makes antibodies to help protect you from infections.
• Sometimes, it can make mistakes, producing antibodies that target your own tissues. This happens in autoimmune disorders.
• There are five main classes of antibodies.
• Each class has a different role in protecting your body.
• The immunoglobulins test measures three of these: IgG, IgA, and IgM.
• Measuring them can help show if your immune system is working as it should be.
  

What are immunoglobulins?

Immunoglobulins are also known as antibodies. Your immune system protects you by making antibodies to attack substances that are foreign to your body and could be harmful to you. This includes infections like viruses and bacteria.

It does this by targeting marker antigens which are found on the surfaces of most cells. Cells with marker antigens that are different from your own can be attacked. Antigens can also be found on abnormal cells, such as cancer cells. Sometimes, your body mistakenly makes antibodies against your own cells. This happens in autoimmune disorders.

Each antibody is made to recognise and attach to only one particular target antigen, or a very small group of closely related targets.

Antibodies are made by white blood cells called B cells.

• Your immune system spots an antigen on a cell that it recognises as harmful.
• Each B cell recognises a specific antigen. When it finds a matching antigen, it becomes activated. This causes the B cells to multiply and split into two types:
  • Plasma cells – these produce one specific antibody and can live in the bone marrow for many years, sometimes for a lifetime.
  • Memory B cells – when your body encounters a foreign antigen for the first time it creates memory B cells. If the same antigen is encountered again, the immune system can respond much faster by producing large amounts of the same antibody. Memory B cells make better antibodies over time with more exposure.
• Antibodies are released through plasma cells. The antibodies attach to the antigens on the target cells and block potential infections from harming you.
• Antibodies also mark them so other immune cells can find and destroy them.

Types of immunoglobulins

There are five main classes of immunoglobulins. Each class represents a group of antibodies and has a slightly different role.
The immunoglobulin test measures the total amount of three of these – IgA, IgM, and IgG. IgD is not fully understood and is not routinely measured. IgE is involved in allergic reactions and is usually measured separately when specifically investigating allergies and possible parasites infections. For more see Immunoglobulin IgE.

Immunoglobulin G (IgG)

IgG is the most common antibody in the blood, making up about 70–80% of all immunoglobulins. It provides long-term protection against infections.
When you are first exposed to a microorganism or other foreign substance (antigen), your body makes specific IgG antibodies. These increase over several weeks, then fall to a lower level and remain in the body.
If you are exposed to the same antigen again, your immune system remembers it and quickly makes more of the same IgG antibodies. In people with a healthy immune system, this often prevents the infection or makes it much less severe.
Vaccines work by using this natural immune memory. They expose the immune system to a harmless form or part of a virus or bacteria so the body can make protective IgG antibodies without causing the disease. These are produced by plasma cells.

Immunoglobulin A (IgA)

IgA makes up about 15% of the antibodies in the blood. It is also found in saliva, tears, mucus, the lungs, the digestive tract and breast milk.
IgA helps protect the surfaces of the body that are exposed to the outside environment, especially the respiratory and gastrointestinal tracts. There are two IgA subclasses, IgA1 and IgA2, but they are not of clinical use.

Immunoglobulin M (IgM)

IgM is the first antibody the body makes when a new infection begins. It provides early, short-term protection. Your immune system produces small amounts of IgM all the time as part of normal background activity. When an infection is detected, specific IgM levels rise sharply, and some B cells switch to producing IgG to strengthen the response. IgM levels rise during the first few weeks of an infection and then fall as IgG levels increase.

Immunoglobulin G 4(IgG4)

There are four IgG subclasses: IgG1, IgG2, IgG3, and IgG4. Measuring these subclasses is rarely helpful. However, IgG4 behaves differently from other antibodies and is tested when a condition called IgG4-related disease is suspected. This involves inflammation and scarring in various organs. For more, see Immunoglobulin G 4 (IgG4).

Why get tested?

An immunoglobulin test is sometimes called a quantitative immunoglobulin blood test because it measures the amount (quantity) of the main immunoglobulins (antibodies) in your blood. The test helps assess how well your immune system is working and is used to investigate conditions that affect antibody production. Your doctor may order this test if they suspect:

• An immune deficiency disorder, where your body does not make enough antibodies. This includes inherited immune disorders and immune deficiencies caused by medications, blood cancers, or other health conditions.
• A blood cancer or related disorder, where abnormal plasma cells or white blood cells produce too much or an abnormal type of antibody. Examples include multiple myeloma, chronic lymphocytic leukaemia (CLL) and lymphoma.
• Autoimmune diseases, where your immune system attacks your body's own tissues. These conditions can cause immunoglobulin levels to increase. Examples include systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), Sjögren syndrome and autoimmune hepatitis.
• A long-term infection, such as HIV, chronic hepatitis, or tuberculosis (TB), which can stimulate your immune system to produce more antibodies.
• Liver disease, including cirrhosis, primary biliary cholangitis, and autoimmune hepatitis, which can affect immunoglobulin levels. Typically, there is a rise in both IgG and IgA.
• Kidney disease, where immunoglobulins may be lost in the urine or their levels altered.
• Protein losing enteropathy - a collection of diseases can lead to loss of immunoglobulins from the bowel caused by NSAIDs (anti-inflammatory drugs), and a type of inflammatory bowel disease called collagenous colitis.
• Long-term inflammatory conditions, which can also cause immunoglobulin levels to increase.

Quantitative immunoglobulin tests are often repeated over time to see how well treatment is working or whether a condition is changing.

The immunoglobulins test may be ordered along with others, such as a serum and/or urine protein electrophoresis. When this is the case, a urine sample may be collected in addition to blood.

In some situations, your doctor may need to test a sample of cerebrospinal fluid (CSF) – the fluid that surrounds your brain and spinal cord. This is used when it is thought there could be inflammation or an abnormal immune response within the brain or spinal cord (the nervous system). It helps distinguish diseases that are occurring inside the nervous system from conditions affecting the rest of the body. Multiple sclerosis is the most common reason for CSF immunoglobulin testing. A CSF is collected through a lumbar puncture, or spinal tap.

Having the test

Sample

• Blood
• Cerebrospinal fluid (CSF)
• Saliva

Any preparation
None

Your results

Your doctor will look at your IgG, IgA and IgM levels together. The results are interpreted together with your symptoms, medical history and the results of other tests. High or low immunoglobulin levels can occur in many different conditions. An immunoglobulin test on its own cannot diagnose a specific disorder.

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 several conditions that are associated with increased and decreased immunoglobulins.

High levels - polyclonal or monoclonal

Your results may be described as being polyclonal or monoclonal.

Polyclonal
Normally, your body makes many different antibodies to protect you from different infections and other harmful substances. These are called polyclonal immunoglobulins.

If polyclonal immunoglobulin levels are higher than normal, it means your immune system is active. In this situation there is typically a marked increase in all class of immunoglobulin.

Monoclonal
Sometimes, a single group of plasma cells starts making large amounts of one identical antibody. This is called a monoclonal immunoglobulin. A monoclonal immunoglobulin is not a normal immune response. It may be found in conditions such as MGUS (monoclonal gammopathy of undetermined significance), which often causes no symptoms, or in blood disorders such as multiple myeloma.

Low levels
Having fewer antibodies than normal is classified as being secondary (acquired) or primary (inherited).

Secondary (acquired)

Acquired deficiencies are the result of some underlying condition and termed secondary immunodeficiencies. The most common causes of low immunoglobulins are secondary conditions that either affect the body's ability to produce immunoglobulins or increase the loss of protein from the body.

Primary (inherited)

These are rare disorders in which the body is not able to produce one or more classes of immunoglobulins. They may affect the production of all immunoglobulins, a single class, or one or more subclasses.

Reference intervals - comparing your results to the healthy population

Your results will be compared to reference intervals (sometimes called a normal range).

• Reference intervals are the range of results expected in healthy people.
• They are used to provide a benchmark for interpreting a patient's test results.
• When compared against them, your results may be flagged high or low if they sit outside this range.
• Some reference intervals are harmonised or standardised, which means all labs in Australia use them.
• Others are not because for these tests, labs are using different instruments and chemical processes to analyse samples.
• Always compare your lab results to the reference interval provided on the same report.

If your results are flagged as high or low this does not necessarily mean that anything is wrong. It depends on your personal situation.

Reference intervals for immunoglobulins vary between labs so you will need to go through your results with your doctor.

Questions to ask your doctor

The choice of tests your doctor makes will be based on your medical history and symptoms. It is important that you tell them everything you think might help.
You play a central role in making sure your test results are accurate. Do everything you can to make sure the information you provide is correct and follow instructions closely.
Talk to your doctor about any medications you are taking. Find out if you need to fast or stop any particular foods or supplements. These may affect your results. Ask:

• Why does this test need to be done?
• Do I need to prepare (such as fast or avoid medications) for the sample collection?
• Will an abnormal result mean I need further tests?
• How could it change the course of my care?
• What will happen next, after the test?
  

More information
Pathology and diagnostic imaging reports can be added to your My Health Record. You and your healthcare provider can now access your results whenever and wherever needed.
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