Immunoglobulin M (IgM)

IgM (immunoglobulin M) is a type of antibody that your body makes to help you fight off infections. It’s the first antibody your immune system makes when fighting off viruses, bacteria, parasites or other harmful invaders while your body prepares additional defenses. It’s also the first antibody your immune system starts to develop as a fetus. “Ig” is short for immunoglobulin, which is another name for antibody.

Antibodies are molecules that have a unique shape. This shape fits one specific antigen in a similar way to how a key fits a lock. Antigens are molecules that let your body know whether a cell or an organism is part of your own body (“self”) or foreign (“non-self”) and potentially dangerous. When an antibody comes across an antigen that it fits — like on the surface of a virus or bacterium — it tells your immune system that it’s found a potential problem. Your immune system can then take action to eliminate the harmful substance (pathogen) by flushing it out of your body or destroying it altogether.

IgM is unique from other antibodies because it usually exists as five IgM antibodies joined together, making it the largest antibody (known as a macroglobulin). This helps it find even small amounts of pathogens. It also allows it to clump pathogens together (agglutination), making it easier for other immune cells to find and destroy them.

Where are IgM antibodies in your body?

IgM is found in your blood and lymph, either on its own or attached to B cells. It’s too large to move out of your blood vessels into your tissues. It’s also too large to move across the placenta to a fetus, so newborns don’t get protection from their mothers’ IgM antibodies.

What do IgM antibodies do?

IgM is made during your primary immune response — that is, the first time your body encounters a particular pathogen. IgM antibodies respond to potentially harmful substances by:

• Alerting other immune cells: IgM antibodies can attach to pathogens and activate the complement cascade. This attracts complement proteins, a group of immune cells that react with one another to damage and destroy pathogens.
• Neutralizing them: If an IgM antibody attaches (binds) to a pathogen, it can prevent it from attaching to and entering your body’s cells.
• Acting as a B-cell receptor: B-cell receptors activate B cells to make more antibodies that recognize a specific antigen.
• Agglutinating them: IgM antibodies can bind to an antigen at one end while attached to other IgM antibodies at the other end. This causes pathogens like bacteria to clump together, or agglutinate. This process makes it easier for other immune cells to destroy them.

Agglutination by IgM antibodies is one of the reasons that getting a blood transfusion of the wrong blood type is so dangerous — IgM agglutinates the proteins on the mismatched blood type, which are foreign to your body. They clump together, causing blood clots.

What’s the structure of IgM antibodies?

Immunoglobulins are made up of chains of proteins arranged in a “Y” shape. Each antibody is different at the open (forked) end, called the receptor or Fab region. This region has a unique shape that recognizes the antigen on the surface of viruses, bacteria or other potentially harmful substances. It attaches (binds) to these antigens at an epitope (area it can latch onto) to alert your immune system that it found something harmful.

All antibodies of the same type (IgA, IgD, IgE, IgG and IgM) have the same chain of proteins at the straight end, called the Fc or constant region. The Fc region attaches to immune cells. When immune cells find an IgM antibody that’s bound to an antigen, it starts a reaction to destroy the harmful invader.

In your blood, IgM exists as a pentamer. An IgM pentamer is a molecule with five IgM antibodies stuck together at the Fc ends, with the forked ends facing outward — you can think of it as looking like a star or a snowflake. This gives IgM the advantage of having many receptors that it can use to grab onto large pathogens with many epitopes, like some bacteria. It also helps them find even low levels of harmful substances.

Single IgM antibodies (monomers) are attached to the surface of B cells and act as B-cell receptors. These antibodies allow the B cells to identify harmful invaders and make more antibodies to defend your body.

What tests are there for IgM?

Your provider can order immunoglobulin tests to check your levels of IgM and other antibodies. This is a blood test that can help diagnose immune system diseases and infections.

What are normal IgM levels?

The range of normal IgM levels is between 40 and 250 mg/dL (milligrams per deciliter). These numbers can vary by lab. They also vary by age and are lower in infants younger than 9 months.

What causes high IgM?

The most common cause of high IgM antibodies is having a recent illness (infection). Other, rare causes include:

• Waldenström macroglobulinemia: A rare blood cancer with high levels of abnormal IgM
• Hyper-IgM (HIgM) syndromes: Genetic disorders that cause you to have high levels of IgM but low levels of other antibodies, like IgG
• Schnitzler’s syndrome: An inflammatory disease that causes frequent hives, fever, and bone and joint pain (high levels of abnormal IgM can be a sign of Schnitzler’s syndrome)
• Multiple myeloma: A rare blood cancer

What causes low IgM?

Diseases that affect your immune system’s ability to make antibodies and other immune cells can cause low levels of IgM. These include:

• Hypogammaglobulinemia: These conditions prevent you from making enough B cells, or prevent B cells from maturing and making antibodies. They include common variable immunodeficiency (CVID), autosomal recessive agammaglobulinemia (ARA) and X-linked agammaglobulinemia (XLA).
• Selective IgM deficiency: In this condition, you have low levels of IgM but normal levels of other antibodies.

What are the symptoms of conditions that affect IgM?

If you have a low level of IgM antibodies, you can get frequent infections, including:

• Sinusitis
• Pneumonia
• Bronchitis
• Ear infections

You might also get frequent infections if you have high levels of IgM antibodies, especially if they’re abnormal (which means they won’t function properly). Additional symptoms of high levels of IgM antibodies include:

• Frequent fevers
• Chronic hives (urticaria)
• Joint or bone pain
• Enlarged liver
• Enlarged spleen
• Swollen lymph nodes
• Fatigue

What is the difference between IgG, IgM and IgA?

IgG, IgM and IgA are all common antibodies that fight infection. IgM antibodies are the first to respond to an infection while your body makes IgG antibodies, which come in to fight later in the infection. IgA fights infections in your mucous membranes (like your intestines).