Fractionation of Serum Proteins in Hyperproteinemia, with Special Reference to Multiple Myeloma.

Investigation of the serum proteins in disease is handicapped by lack of clinically applicable methods for resolving the complex system of proteins present in blood serum into homogeneous components. The only fractionation now possible is into groups of proteins having like solubility characteristics or electrophoretic mobilities or sedimentation constants (depending upon the method employed) but varying in other properties and in composition (1). However, these methods, if rigidly standardized, give reproducible results and, in certain diseases, characteristic divergencies from normal patterns. The separations therefore, though arbitrary, have at least empirical value. The present study -deals with the empirical application of Howe's method (2) and the electrophoretic technique (3, 4) to fractionation of the serum proteins in various diseases presenting hyperproteinemia. Multiple myeloma is of special interest in this connection. Not only is the incidence and degree of hyperproteinemia unusually high (5, 6, 7, 8), but there is extraordinary variability in the composition of the protein increment (7, 9), as indicated by fractional precipitation with neutral salts (5, 10, 11, 12), by electrophoresis (4, 13), and by ultracentrifugation (13). The significance of these peculiarities has not been made clear. To provide a common basis for consideration of our findings in hyperproteinemia, we have first cited results obtained in normal adult subjects. Serum protein partitions in a variety of chronic infections and in cirrhosis are then recorded to illustrate the uniform plan in distribution of globulin subfractions which characterizes hyperproteinemia of all such etiology. Some of our cases with elevated serum protein levels due to multiple myeloma likewise showed this conventional fractional distribution. Others, however, presented certain distinctive anomalies in both the Howe and electrophoretic patterns, which were found to be due in large part to BenceJones proteinemia and to be of value in diagnosis.