Studies of Bence Jones proteins by immunonephelometry

Plasma cell dyscrasia is a disease caused by a monoclonal population of plasma cells. Most often the workup for this disease is prompted by the appearance of a paraprotein in serum, but a significant number of cases exhibit only a Bence Jones protein. Immunofixation electrophoresis is the most sensitive method presently used for identifying Bence Jones proteinuria. This methodology is laborious, expensive, and difficult to interpret. As a result, quantitative immunochemical methodologies have been suggested for measuring Bence Jones proteinuria. In this manuscript, it is demonstrated by rate nephelometry that: (1) although serum polyclonal immunoglobulins are accurately measured as compared to the calibration material, serum monoclonal immunoglobulins are not; (2) measurement of immunoglobulins in the urine of patients with generalized proteinuria is biased towards an increased number of light chains or a decreased number of heavy chains; and (3) Bence Jones proteins react with the assay antibodies differently from the calibration material and from one another. It is concluded that, although there is a qualitative relationship between concentrations of Bence Jones proteins and immunoglobulins used for calibration, measurement of absolute levels of Bence Jones proteins using currently available methods will lead to inaccuracies resulting from peculiarities between the antibody-antigen reaction and because of the spillover of polyclonal free light chains into urine. Nevertheless, the data provides credence for studies suggesting that measurement of the kappa/lambda ratio in serum and urine may be a reliable way to identify Bence Jones proteins by automated assays.