The differential diagnosis of monoclonal gammopathy includes monoclonal gammopathy of undetermined significance (MGUS), multiple myeloma, solitary plasmacytoma of bone or extramedullary plasmacytoma, Waldenström macroglobulinemia, lymphoma, CLL, and primary systemic amyloidosis. These individual disorders are described elsewhere in this text; however, there are a few points to be made about the M protein itself and MGUS. These disorders can produce intact immunoglobulins (IgG, IgM, IgD, or IgE), κ-, or λ-light chains alone or in combination with intact immunoglobulins, and rarely heavy chains only. The monoclonal protein is usually detected as a discrete band in the γ or β region in serum or urine protein electrophoresis (M spike) and then characterized and confirmed by immunofixation electrophoresis (IFE). Monoclonal antibodies have been associated with a wide variety of bacterial antigens as well as various other antigens, including thyroglobulin, von Willebrand fac tor, and lactate dehydrogenase; however, for most M proteins, the antigen is not recognized. A variety of other disorders are also associated with an M protein (Table 1), including connective tissue disorders, neurologic disorders (including POEMS [polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes] syndrome), renal disorders, and some infections such as HCV and HIV. Patients undergoing bone marrow and solid-organ transplants in which there is immune suppression are also occasion ally observed to have M proteins, but these are usually transient and disappear with recovery of the immune system. Acquired immune disorders such as acquired C1 inhibitor deficiency, type 2 acquired angioedema, and acquired von Willebrand syndrome have also been associated with M proteins.
Table1. Diseases Associated With Monoclonal Gammopathy
