Methodologic differences in values for M-proteins in serum, as measured by three techniques.

Accurate and reproducible measurement of M-proteins is essential for managing patients with monocional gammopathies, but serum protein electrophoresis, radial immunodiffusion, and electroimmunodiffusion yield comparatively divergent results. We have studied these differences and their causes. Sera from cases of IgG-monoclonal gammopathy, IgA-monoclonal gammopathy, and IgM-monoclonal gammopathy were assayed by each of the three techniques. Results indicated inter-method discrepancies as great as fivefold for all proteins studied. For IgG-monoclonal gammopathy, radial immunodiffusion values were less consistently so. For IgA-monoclonal gammopathy, both radial immunodiffusion and electroimmunodiffusion gave lower results than did serum protein electrophoresis. For IgM-monoclonal gammopathy, results were variable, but values by radial immunodiffusion tended to be higher than, and electroimmunodiffusion comparable to, those for serum protein electrophoresis. The differences were not correlated with protein abundance, serum freshness, immunoglobulin class, light-chain type, ultracentrifugal characteristics, or electrophoretic mobility. Clearly, values for M-protein concentration depend on the techniques used to obtain them. We postulate that subclass differences may contribute to the diversity of radial immunodiffusion results, and that for electroimmunodiffusion the fixed electrophoretic mobility of M-proteins leads to unpredictable results. We conclude that serum protein electrophoresis is the best of the three assay techniques for M-proteins.