Free Monoclonal Immunoglobulin Light Chains in Serum and Urine

Author(s): Professor. Gurmukh Singh

Plasma cells, normal, reactive, and malignant, generally produce more light chains than heavy chains of immunoglobulins. The excess light chains, polyclonal and monoclonal, can be detected in serum and urine. Qualitative and quantitative ascertainment’s of light chains in serum and urine are instrumental in diagnosis and monitoring of plasma cell disorders in general, and multiple myeloma in particular. There are differences in biological behaviors of kappa and lambda light chains, and there is a preference for kappa light chains. Antisera/antibodies to light chains fall into two groups: (a) reacting with free light chains as well as those part of an intact immunoglobulin, or (b) specific to free light chains only. The commercially available antisera/antibodies to free light chains are not equivalent and differ in their reactivity with light chains.

Measurement of serum free light chains has been promoted for screening for monoclonal gammopathies and inaccurately touted as replacing the need for urine examination. Other purported uses for serum free light chain measurement have been for determination of stringent complete response to treatment in multiple myeloma, and for diagnosing myeloma defining conditions, however, the validity of these uses has been challenged. Use of serum free light chain measurement in other disorders with monoclonal gammopathy, e.g., amyloidosis has not been fully explored.

Quantification of serum free light chains is broadly accepted for monitoring of light chain multiple myelomas and for diagnosis of light chain predominant multiple myelomas. Ascertainment of monoclonal light chains in serum and urine has been proposed to serve as marker for residual disease. A gel-based assay for detection of monoclonal light chains in serum, using antisera specific to free light chains, has been shown to be more sensitive than a mass spectrometry-based assay. Similarly, urine immunofixation electrophoresis using antisera specific to free light chain has demonstrated superior sensitivity to monoclonal light chains in urine. The usefulness of antisera to combination of heavy and light chains, “Hevylite®” in detecting residual disease remains to be examined.

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