Size, shape, and hydration of a self-associating human IgG myeloma protein: axial asymmetry as a contributing factor in serum hyperviscosity.

Studies of sedimentation, diffusion, viscosity, and buoyant density have been carried out on a human IgG1-lambda myeloma protein (IgG-MIT) isolated from the serum of a patient with multiple myeloma and the hyperviscosity syndrome. In comparison with pooled normal IgG, IgG-MIT exhibits smaller sedimentation and diffusion coefficients, a larger intrinsic viscosity, and a larger frictional ratio. The preferential hydration of IgG-MIT in cesium chloride was found to be within the range of values typically observed for globular proteins. The data are consistent with prolate ellipsoid geometry, and suggest that the axial ratio of the IgG-MIT monomer is approximately 50% greater than that typically observed for IgG. The concentration dependencies of the hydrodynamic data for IgG-MIT confirm the previous finding of reversible, concentration-dependent self-association for this protein. IgG-MIT thus represents the first reported instance of an IgG paraprotein for which in vivo hyperviscosity effects appear attributable to a twofold mechanism involving geometric asymmetry and concentration-dependent polymerization. The results are discussed in terms of the significant heterogeneity in molecular dimensions which may exist among normal IgG proteins.