Clinical Significance

IgM, primarily present as a pentamer, is the first immunoglobulin class produced during an initial immune response and antigen-IgM complexes actively fix complement. The large molecular size of the pentamer enables direct cross-linking and agglutination of particulate and cellular antigens.  Because IgM is involved in primary immune response, presence of IgM is useful in assessing whether a particular infection is acute (IgM present) or chronic (IgG predominate class present).  Additionally, IgM is the first immunoglobulin class to be synthesized by a fetus or newborn.  IgM antibodies do not cross the placenta.  Polyclonal IgM increases may indicate a viral infection, such as viral hepatitis or infectious mononucleosis, or the early response to bacterial or parasitic infection.  Elevated levels are also seen with hyper-IgM dysgammaglobulinemia, active sarcoidosis, collagen vascular disease, and nephrotic syndrome.   Monoclonal IgM increases are seen in Waldenstrom’s macroglobulinemia, malignant lymphoma, reticulosis, and cold agglutinin hemolysis disease.  Small IgM monoclonal bands can accompany a variety of neoplasms, particularly of the GI tract.  Decreased IgM levels are usually not due to primary IgM deficiency.  Secondary IgM deficiency may be associated with IgA, or IgG type multiple myeloma, protein-losing enteropathies, burns, or immunosuppressive therapy. IgM deficiency is associated with increased, recurrent infections..