Immunoglobulin M (IgM) is one of the five major classes of antibodies, or immunoglobulins, that the immune system produces. It is the first type of antibody to appear in response to an initial exposure to a foreign substance, known as an antigen. Because of its rapid appearance, it is often considered the immune system’s first line of defense against a new infection. Plasmablasts, a type of immune cell found in the spleen, are the primary source of IgM production in humans and other mammals.
IgM’s Function in a Primary Immune Response
When the body first encounters a pathogen, such as a virus or bacterium, it initiates a primary immune response, and B cells begin to synthesize IgM. The structure of IgM is unique among immunoglobulins; it typically exists as a large pentamer, which means it is composed of five individual antibody units joined together. This large, multi-unit structure is stabilized by a small protein called a joining (J) chain.
The large, complex shape of the IgM pentamer gives it a significant advantage in fighting infection. It possesses ten antigen-binding sites, allowing it to bind to multiple pathogens at once. This multi-armed characteristic makes IgM highly efficient at a process called agglutination, where it clumps pathogens together. This clumping action makes it easier for other components of the immune system to identify and eliminate the invaders.
This large size also makes IgM particularly effective at activating the complement system, a cascade of proteins in the blood that helps to destroy pathogens. This activation leads to the opsonization of antigens, which is the process of marking them for destruction by phagocytic cells, and cytolysis, the direct rupture of pathogen cell membranes. Because of its size, about 80% of IgM remains within the bloodstream, where it provides protection against microorganisms that have invaded the blood.
The Diagnostic Use of IgM Testing
Because IgM is the first antibody to appear during the course of a new infection, its presence in a blood sample is a strong indicator that a person has a recent or currently active infection. For example, the detection of IgM antibodies in a patient’s serum can signify a recent infection, while its presence in a newborn’s serum suggests an infection that occurred in the womb, such as congenital rubella or syphilis. This is because IgM is too large to cross the placenta from mother to fetus, so any IgM in a newborn’s blood must have been produced by the baby itself.
To understand the stage of an infection, clinicians often look at the levels of both IgM and another antibody, Immunoglobulin G (IgG). IgM levels typically rise quickly at the beginning of an infection and then decline as the immune response progresses, usually within a few weeks. In contrast, IgG antibodies are produced later in the response. Their levels rise more slowly but can remain elevated for a much longer period, often for years, providing long-term immunity.
This dynamic relationship between IgM and IgG allows for a more precise diagnosis. If a blood test shows the presence of IgM but little or no IgG, it is likely that the infection is very recent. If both IgM and IgG are present, the infection is likely in a later stage or has recently passed. The presence of IgG without IgM generally indicates a past infection or immunity from a vaccination. This distinction helps healthcare providers determine the timeline of an illness.
Conditions Associated with Abnormal IgM Levels
Deviations from the normal range of IgM in the blood can be associated with various medical conditions.
High IgM Levels
Elevated levels of IgM are most commonly linked to a current or recent infection, as the body ramps up production of this antibody to fight off the invading pathogen. However, persistently high IgM can also be a sign of other health issues. Certain autoimmune diseases, where the immune system mistakenly attacks the body’s own tissues, can lead to increased IgM. Rheumatoid arthritis is one such condition where this can occur.
In rarer cases, significantly high IgM levels may indicate a specific type of blood cancer known as Waldenström macroglobulinemia. This condition is characterized by the overproduction of IgM by cancerous plasma cells. Another rare condition, Schnitzler’s syndrome, also includes the presence of IgM as a required diagnostic criterion.
Low IgM Levels
Abnormally low levels of IgM can point to a compromised immune system. This may be caused by a primary immunodeficiency disorder, which is a genetic condition that impairs the immune system’s ability to function correctly. One such disorder is known as selective IgM deficiency, where the body does not produce enough of this specific antibody, making an individual more susceptible to infections.
Low IgM can also be acquired as a result of certain diseases or medical treatments that suppress the immune system. Conditions that affect protein production or lead to protein loss can also result in decreased IgM levels. Because IgM provides protection against blood-borne infections, a deficiency is often associated with recurrent and sometimes severe infections, such as septicemia.