Patients with abnormal IgM levels: assessment, clinical interpretation, and treatment

Abstract

INTRODUCTION This review of the role of IgM in cognate immunity is part of a series on ambulatory diagnoses and management of primary immune deficiency diseases edited by Chitra Dinakar, University of Missouri.1 IgM is phylogenetically the earliest antibody class identified and the first immunoglobulin isotype to appear in the circulation after exposure to a new antigen. IgM plays an important role in the ontogeny of B cells and in early cognate immune responses.2 VDJ rearrangement of the immunoglobulin heavy chain occurs at the pre– B-cell stage, when light chains are still of the surrogate type ( 5/VpreB). Further maturation leads to immature B cells, which express surface IgM and IgD and carry and light chains, creating a functional B-cell receptor that allows antigen recognition and further development into unswitched memory B cells (IgM /D , CD27 ). After interaction with the T-cell receptor of antigen-specific CD4 T cells via major histocompatibility complex II and costimulatory molecules (CD40 ligand [CD40L]/CD40, inducible costimulator [ICOS]/ICOS ligand), mature B cells undergo isotype switching, resulting in B cells expressing CD27 and IgG, IgA, or IgE. Whereas IgM is responsible for rapid and early generation of antibody, long-term humoral immunity is initiated by the production of high-affinity IgG or IgA antibody. The demonstration of IgM antibodies to a specific infectious agent can be used as an indicator of recent infection. The presence of IgM in cord blood ( 20 mg/dL) may indicate prenatal infection because IgM antibody cannot be acquired from the mother by transplacental passage. In infants, IgM serum levels increase rapidly from a mean of 11 mg/dL at term to 55 mg/dL at 1 year of age. By 2 years, IgM concentration is approximately 60% of that in adults. IgM is expressed as a monomer on the surface of naive and mature unswitched B cells, where it forms the antigen receptor complex together with the coreceptors Ig and Ig . If secreted, most IgM forms a pentameric complex, which stays mostly (70% to 80%) intravascular. Its half-life is approximately 6 days, in contrast to IgG, which has a half-life of 21 to 28 days. IgM antibodies are uniquely efficient in agglutination and are highly avid because of their multimeric nature and strong complement fixation.