Calcium binding by a myeloma protein.

We describe a patient with immunoglobulin G (IgG)-kappa myeloma and severe, long-standing, asymptomatic hypercalcemia. Serum nonprotein-bound calcium concentration was 5.2 mg/dl (normal 4.2 to 5.0 mg/dl) at a time when total serum calcium concentration was 17.8 mg/dl. The patient's myeloma protein, IgGCAB, and Fab fragments of IgGCAB migrated more anodally when agarose gel electrophoresis was performed in the absence of calcium ion than when electrophoresis was performed in the presence of calcium ion; 60 other myeloma proteins did not demonstrate such behavior. Purified IgGCAB bound 1.5 calcium ions with a single dissociation constant of 1.2 X 10(-4) M. We speculate that the rare syndrome of myeloma and high protein-bound calcium is due to binding of calcium to variable regions of the myeloma antibody molecules.