The various monoclonal Gammopathies

Monoclonal gammopathies are defined by the presence of a monoclonal immunoglobulin (Ig) in serum or urine. This situation indicates the presence of a group of immune cells, termed a clone, that all produce the same Ig molecule. The clone may consist of malignant cells, which damage their environment. In these cases the monoclonal gammopathy results from malignant proliferation. The main ones are myeloma and Waldenström’s macroglobulinaemia. In many cases, the cells of the clone are not aggressive: these « benign » proliferative disorders are actually intermediate situations and can progress to overt malignant disease. They are termed monoclonal gammopathies of undetermined significance or MGUS.

Spatial representation of an immunoglobulin molecule of the IgG class

Frequency

The detection of a monoclonal Ig is a common occurrence, as it affects about 1% of people over 25 years of age. It is detected slightly more often in men than in women, rarely in people of East Asian and Southeast Asian descent, and about twice as frequently in the black population as in the white population. Age is a key determinant: the prevalence of monoclonal Ig is about 0.2% before the age of 50 years and increases steadily with age, reaching 6% in the over 70 year-old population and exceeding 9% in people over the age of 90 years.

Distribution by type of monoclonal Ig

The IgG class accounts for about two-thirds of monoclonal Igs. Monoclonal IgMs and IgAs occur at roughly equal frequency (15%–20%). In about 10% of gammopathies, only light chains are produced. Double or multiple gammopathies are not rare findings. However, monoclonal IgD is uncommon, and monoclonal IgE is very rare.

The prevalence of kappa light chains versus lambda light chains mirrors the 2:1 ratio found in normal serum Igs. This applies regardless of the associated heavy chain, except in the case of IgD, which is almost always associated with lambda light chains.