Monoclonal Gammopathy of Undetermined Significance

Monoclonal gammopathy of undetermined significance (MGUS) is a common premalignant plasma-cell proliferative disorder that is present in approximately 5% of the general population over the age of 50 years.1-4 This disorder is important not only because it is the precursor to plasma-cell cancers, including multiple myeloma, solitary plasmacytoma, and Waldenström’s macroglobulinemia, but also because it is causally related to numerous serious nonmalignant disorders, collectively referred to as monoclonal gammopathy of clinical significance (MGCS).5 MGUS is characterized by a limited yet monoclonal proliferation of plasma cells secreting abnormal levels of immunoglobulins (antibodies) that are identical to each other, with the same amino acid sequence, referred to as monoclonal (M) proteins.6 These secreted M proteins are best appreciated as fully functioning human antibodies present in high concentrations that fortunately lack affinity to self-antigens (autoantibody characteristics) in most persons. As a result, MGUS remains asymptomatic in the absence of malignant transformation in most people. However, there is potential for serious harm if the M protein has or develops affinity for one or more organs in the body, resulting in MGCS.