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Monoclonal Gammopathy of Undetermined Significance (MGUS)


James R. Berenson

, MD, Institute for Myeloma and Bone Cancer Research

Last full review/revision Sep 2019| Content last modified Sep 2019
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A monoclonal gammopathy of undetermined significance is a buildup of monoclonal antibodies produced by abnormal but noncancerous plasma cells.

Plasma cells develop from B cells (B lymphocytes), a type of white blood cell that normally produces antibodies (immunoglobulins). Antibodies are proteins that help the body fight infection. If a single plasma cell multiplies excessively, the resulting group of genetically identical cells (called a clone) produces a large quantity of a single type of antibody. Because this antibody is made by a single clone, it is called a monoclonal antibody and also is known as the M-protein. People with a large quantity of the M protein often have low levels of other antibodies making them more susceptible to infections. Immunoglobulins are sometimes referred to as gamma globulins, so a disorder may be called a gammopathy. (See also Overview of Plasma Cell Disorders.)

In general, monoclonal gammopathy of undetermined significance (MGUS) occurs in more than 5% of people older than 70, but it does not cause significant health problems unless it progresses to myeloma or a related serious B-cell disorder.

This disorder does not usually cause symptoms, so it is almost always discovered by chance when laboratory tests are done for other purposes, such as to measure protein in the blood. However, the monoclonal antibody can bind to nerves and lead to numbness, tingling, and weakness. People with this disorder also are more likely to have bone loss and fractures.

The M-protein levels in people with MGUS often remain stable for years—25 years in some people—and do not require treatment. However, if evaluation shows evidence of significant loss of bone density (osteopenia or osteoporosis), doctors may recommend treatment with bisphosphonates.

For unknown reasons, in about one quarter of people with this disorder, there is a progression to a cancer, such as multiple myeloma, macroglobulinemia, or B-cell lymphoma, often after many years. This progression cannot be prevented. About twice a year, people with a monoclonal gammopathy of undetermined significance are usually monitored with a physical examination and blood and sometimes urine tests to determine whether progression to cancer is beginning to occur. If progression is detected early, symptoms and complications of the cancer may be prevented or treated sooner.

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