Why is Immunoglobulin M (IgM) Low? Causes, Symptoms, and What to Do

A low immunoglobulin M (IgM) result means your blood contains less of the antibody your immune system usually makes first when it meets a new germ. In many people a mildly low IgM causes no problems and is found by chance; when it matters, the usual reasons are a medicine or illness that suppresses antibody production (such as a blood cancer or immune-suppressing drugs), or an uncommon immune condition called selective IgM deficiency. A high IgM result has a different list of causes, from recent infections such as mononucleosis to blood disorders such as Waldenström macroglobulinemia; both are covered below.

What IgM is and how it is measured

Immunoglobulins are antibodies, proteins made by B cells (a type of white blood cell). IgM is "the first immunoglobulin isotype secreted during an initial immune response" and acts as a first line of defence against microbes. The test is an ordinary blood draw; IgG, IgA and IgM are usually measured together by a method called nephelometry. You may be asked not to eat or drink for 4 hours beforehand.

Typical adult reference range (MedlinePlus):

Ranges vary between laboratories and methods, and children are compared with age-matched values, so always read your result against the range printed on your own report.

Causes of low IgM

More common: secondary (acquired) causes

• Immune-suppressing treatment. Immunosuppressant medicines, chemotherapy and radiation therapy can all dampen the immune system, including antibody production. The antipsychotic clozapine is specifically reported to lower IgM.
• Blood cancers. Leukemia and multiple myeloma are listed causes of decreased IgM, and lymphoma must be excluded before low IgM is called a primary problem; cancers that affect the bone marrow, where immune cells are made, weaken the immune system.
• Undernutrition. A shortage of all nutrients, or of just one, can impair the immune system.

Less common: primary (inborn) causes

• Selective IgM deficiency. IgM is low while IgG and IgA are normal. It is defined as IgM more than two standard deviations below the average for age; "complete" deficiency means IgM under 5 mg/dL. Other causes such as leukemia, lymphoma and medicines must be ruled out first, and in children the diagnosis needs months of follow-up.
• X-linked agammaglobulinemia (XLA). A rare inherited condition, almost only in boys, affecting about 1 in 200,000 newborns. People with XLA have very few B cells and make very few antibodies of any type, so IgM is low along with IgG and IgA. Infections usually start after the first one or two months of life, once the mother's antibodies fade.

Because a low IgM can be secondary, a primary diagnosis is made only after other causes are ruled out and the low level is confirmed over time.

Symptoms

A low IgM number does not cause symptoms by itself. Many people with selective IgM deficiency have none at all. When symptoms do occur, they come from weaker protection against infection:

• Repeated bacterial infections, such as sinusitis, bronchitis and pneumonia. Among people with selective IgM deficiency who have symptoms, about 80% present mainly with bacterial infections.
• Allergies. Almost 40% of people with selective IgM deficiency have allergic conditions.
• Autoimmune conditions are more common than in the general population.

What usually happens next

1. Repeat the test to confirm the result is persistent rather than a one-off.
2. Look at IgG and IgA. Low IgM alone points towards selective IgM deficiency or a medicine effect; all three low suggests a broader antibody problem.
3. Complete blood count (CBC) and, when a blood cancer is possible, serum protein electrophoresis and immunofixation.
4. Vaccine response testing. The doctor may measure specific antibodies produced after a vaccine. One-third to one-half of people with selective IgM deficiency respond poorly to the 23-valent pneumococcal polysaccharide vaccine.
5. Review of medicines you take, since several can lower antibody levels.

Treatment depends on the cause. There is no medicine that directly raises IgM. People with recurrent infections and poor vaccine responses may be considered for immunoglobulin replacement, which a clinical immunologist decides on.

High IgM: what it can mean

A raised IgM is usually a sign that the immune system is active. Causes listed by MedlinePlus include infection, mononucleosis, rheumatoid arthritis, lymphoma, multiple myeloma and Waldenström macroglobulinemia.

• Infection, including mononucleosis, is among the everyday reasons, since IgM is made early in an immune response.
• Waldenström macroglobulinemia is a plasma cell cancer in which one clone of cells makes large amounts of a single IgM. The average age at onset is 70, and it is more common in men. Many people have no symptoms and it is found on routine blood tests; when the blood becomes too thick, it can cause bleeding from the skin and mucous membranes, fatigue, headache, confusion and dizziness. Serum protein electrophoresis, immunofixation and immunoglobulin levels are the key tests.
• IgM MGUS (monoclonal gammopathy of undetermined significance) is a symptomless condition in which a single clone of cells makes a small amount of one IgM, without signs of Waldenström macroglobulinemia, myeloma or lymphoma. It is not a cancer, but it is monitored with repeat blood tests because it carries a small yearly risk, around 1.5%, of progressing to Waldenström macroglobulinemia.

Frequently asked questions

What does low IgM mean? It means your blood has less IgM than the laboratory's reference range. It is often harmless and found by chance, but it can reflect a medicine, a blood cancer, or selective IgM deficiency. Your doctor interprets it together with IgG, IgA and your history of infections.

Is low IgM dangerous? Not on its own. The concern is whether you get frequent or severe infections. Many people with low IgM, including some with selective IgM deficiency, have no symptoms.

What causes low IgM levels in adults? The most common reasons are acquired: immune-suppressing treatment, chemotherapy, leukemia, lymphoma, multiple myeloma and undernutrition. Selective IgM deficiency is a rarer, primary cause.

What does elevated or raised IgM mean? Usually a recent or ongoing infection, such as mononucleosis. It can also be seen in rheumatoid arthritis, lymphoma, multiple myeloma and Waldenström macroglobulinemia, so a persistently high value is usually checked with protein electrophoresis.

What does EBV IgG positive, IgM negative mean? In Epstein–Barr virus testing, IgM against the viral capsid antigen (VCA) appears early and usually disappears within 4–6 weeks, while VCA IgG stays for life. A positive IgG with negative IgM therefore usually points away from a very recent infection. Antibodies to the EBNA antigen appear 2–4 months after symptoms start; antibodies to both VCA and EBNA suggest past infection.

Do you need to fast for an IgM blood test? Sometimes. You may be asked not to eat or drink for 4 hours before the test, so follow the instructions you are given.

When to see a doctor

It is worth discussing a low or high IgM result with your doctor soon, especially if you have frequent sinus, chest or ear infections, infections that are slow to clear, or a family history of immune problems. Mention every medicine you take. If a high IgM is found together with unexplained bleeding, headaches or changes in vision, raise this with your doctor promptly. If you develop confusion, fainting or heavy bleeding, seek urgent care.

Sources

1. Quantitative nephelometry test — MedlinePlus (U.S. National Library of Medicine)
2. Selective IgM Deficiency—An Underestimated Primary Immunodeficiency — Frontiers in Immunology (PMC)
3. Selective IgM deficiency — Immune Deficiency Foundation
4. Overview of Immunodeficiency Disorders — Merck Manual Consumer Version
5. X-linked agammaglobulinemia — MedlinePlus Genetics
6. Macroglobulinemia — Merck Manual Consumer Version
7. Laboratory Testing for Epstein-Barr Virus (EBV) — CDC
8. Novel aspects pertaining to the relationship of Waldenstrom macroglobulinemia, IgM MGUS, polyclonal gammopathy and hypoglobulinemia — Clinical Lymphoma and Myeloma (PMC)

Decisions about your health should always be made in consultation with your healthcare provider.