The presence of serum monoclonal immunoglobulin indicates abnormal clonal proliferation of either plasma cells or lymphocytes. Although this finding may be a marker of multiple myeloma or lymphoma, it is often seen in the absence of any clinical signs or symptoms, especially in elderly patients. In these cases the presence of serum monoclonal immunoglobulin is usually considered a benign monoclonal gammopathy, but this diagnosis has been renamed “monoclonal gammopathy of undetermined significance” because long-term follow-up in these patients has shown a high risk (approximately 25%) for the development of myeloma or lymphoma.
The traditional way to detect serum monoclonal immunoglobulin has been protein electrophoresis followed by visual inspection (looking for an abnormal band). This procedure has been automated and is now also performed by capillary electrophoresis for high-throughput testing. No matter how the abnormal band is visualized, its identity as a monoclonal immunoglobulin must be confirmed by use of antibodies specific for immunoglobulin heavy and light chains. This confirmation is necessary because a number of nonimmunoglobulin proteins may masquerade as abnormal bands.
Fibrinogen, probably the most common “pseudo-band,” will of course be present if plasma (rather than serum) protein electrophoresis is performed, but some residual fibrinogen is often present in serum specimens. Other causes of confusion include polymorphisms (such as bis-albuminemia) and in vitro alterations (such as complement degradation).
Serum proteins which migrate outside of the traditional bands are usually present at concentrations well below the detection limit of routine protein electrophoresis (approximately 1 g/L), but in some patients they reach much higher concentrations and may appear as unexplained abnormal bands. This situation has been noted most frequently in patients with increased C-reactive protein. The authors of this case study have shown that tumor markers may also produce such an effect. Although it is not clear exactly why serum protein electrophoresis was performed in this case, laboratorians who review these procedures may want to add elevated tumor markers to the list of things that can mimic a monoclonal immunoglobulin.
Grant/Funding Support: None declared.
Financial Disclosures: None declared.
- © 2008 The American Association for Clinical Chemistry