Clinical Chemistry
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Clinical Chemistry 55: 1646-1655, 2009. First published July 17, 2009; 10.1373/clinchem.2009.123828
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(Clinical Chemistry. 2009;55:1646-1655.)
© 2009 American Association for Clinical Chemistry, Inc.

Cancer Diagnostics

Assessment of Monoclonal Gammopathies by Nephelometric Measurement of Individual Immunoglobulin {kappa}/{lambda} Ratios

Arthur R. Bradwell1,2,a, Stephen J. Harding2, Nicolas J. Fourrier2, Gregg L.F. Wallis2, Mark T. Drayson1, Hugh D. Carr-Smith2 and Graham P. Mead1,2

1 Department of Immunity and Infection, Medical School, University of Birmingham, UK; 2 The Binding Site Ltd., Birmingham, UK.

aAddress correspondence to this author at: Department of Immunity and Infection, Medical School, University of Birmingham, B15 2TT, UK. Fax +0121-430-6482; e-mail a.r.bradwell{at}bham.ac.uk

Background: Currently, monoclonal immunoglobulins are identified and quantified from bands on electrophoretic gels. As an alternative, clonality might be determined by measuring the separate light chain types of each Ig class to allow numerical assessment of Ig'{kappa}/Ig'{lambda} ratios, analogous to free light chain {kappa}/{lambda} ratios.

Methods: Using immunization, tolerization, and adsorption procedures, we prepared sheep antibodies against each of the 6 separate molecules, IgG{kappa}, IgG{lambda}, IgA{kappa}, IgA{lambda}, IgM{kappa}, and IgM{lambda}. Antibody targets comprised the junctional epitopes between the heavy chain and light chain domains. After purification, we assessed the antisera on a Siemens Dade-Behring BNTM II nephelometer for analytical quality and clinical utility.

Results: High-avidity, specific antibodies allowed the production of automated nephelometric immunoassays for each Ig light chain type. Laboratory comparison with serum protein electrophoresis, using dilution experiments, showed lower analytical sensitivity for monoclonal IgG detection but similar or greater sensitivity for IgA and IgM, particularly when the monoclonal bands overlaid transferrin. Results obtained from typing of monoclonal proteins into IgG, A, or M types were comparable with results obtained by immunofixation-electrophoresis methods. Initial clinical studies, in multiple myeloma patients, indicated that Ig'{kappa}/Ig'{lambda} ratios were sometimes more sensitive than immunofixation electrophoresis, provided numerical results, and correlated with changes in disease.

Conclusions: Immunoassays for intact Ig {kappa}/{lambda} pairs are possible and should assist in the management of patients with monoclonal gammopathies.




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Heavy/Light-Chain Analysis of Monoclonal Gammopathies
Clin. Chem., September 1, 2009; 55(9): 1606 - 1608.
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