Immunoglobulin Heavy and Light Chain (HLC) Pairs, IgM Kappa and IgM Lambda
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
Plasma cell proliferative diseases such as multiple myeloma are defined by the monoclonal expansion of bone marrow plasma cells. The abnormal proliferation of clonal cells in the bone marrow can be identified by a skewed ratio of cells synthesizing kappa or lambda immunoglobulin. In addition, the secreted monoclonal immunoglobulin can usually be identified in serum or urine by protein electrophoresis and immunofixation electrophoresis. These electrophoretic procedures can show restricted immunoglobulin migration, characterize the heavy and/or light chains, and quantitate the monoclonal protein. Some monoclonal proteins, however, are difficult to identify and quantitate by electrophoretic assays. The serum concentration of monoclonal free light chains for example may not be high enough to be recognized or quantitated. Immunoassays that are specific for free light chains, as opposed to light chains bound to heavy chains, can quantitate kappa and lambda free light chains. An abnormal ratio of the free light chains can identify excess clonal plasma cell proliferation and the concentration of the monoclonal free light chain can be determined. Another example of proteins that are difficult to identify and quantitate are monoclonal proteins that are intact immunoglobulins (heavy and light chains) that migrate very broadly in the gamma fraction or migrate within the beta or alpha fractions. Immunoassays that are specific for heavy and light chain pairs (HLC) such as IgM kappa or IgM lambda can quantitate the individual HLC pairs and be used to identify abnormal ratios of the HLC pairs and to quantitate the monoclonal HLC pair.
The quantitation of heavy and light chain pairs is useful for:
1. Distinguishing between broadly migrating monoclonal proteins and restricted polyclonal immunoglobulin responses
2. Quantitating monoclonal IgM proteins that are difficult to quantitate on serum protein electrophoresis
3. Providing a more specific quantitation of the monoclonal protein than quantitating total IgM
An elevated IgM heavy and light chain (HLC) pair ratio suggests a clonal proliferation of an IgM kappa clone of plasma cells.
A low IgM HLC pair ratio suggests a clonal proliferation of an IgM lambda clone of plasma cells.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
Heavy and light chain (HLC) quantitation should be used as a complementary method to serum protein electrophoresis.
Small concentrations of monoclonal IgM proteins may not result in an altered HLC pair ratio.
The serum monoclonal protein study (MPSS / Monoclonal Protein Study, Serum) and urine monoclonal protein study (MPSU / Monoclonal Protein Study, 24 Hour, Urine) remain the assays of choice for initial detection of monoclonal proteins.
Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.
0-<5 months: 26-122 mg/dL
5-<9 months: 32-132 mg/dL
9-<15 months: 40-143 mg/dL
15-<24 months: 46-152 mg/dL
2-<4 years: 37-184 mg/dL
4-<7 years: 37-224 mg/dL
7-<10 years: 38-251 mg/dL
10-<13 years: 41-255 mg/dL
13-<16 years: 45-244 mg/dL
16-<18 years: 49-201 mg/dL
> or =18 years: 37-286 mg/dL
IgM kappa: 22-161 mg/dL
IgM lambda: 10-94 mg/dL
MK/ML ratio: 0.7900-4.61
Clinical References Provides recommendations for further in-depth reading of a clinical nature
1. Donato LJ, Zeldenrust SR, Murray DL, Katzmann JA: A 71-year-old woman with multiple myeloma status after stem cell transplantation. Clin Chem 2011 Dec;57(12):1645-1648
2. Bradwell AR, Harding SJ, Fourrier NJ, et al: Assessment of monoclonal gammopathies by nephelometric measurement of individual immunoglobulin kappa/lambda ratios. Clin Chem 2009 Sept;55(9):1646-1655