The interaction of cryoimmunoglobulins with a model surface.

Cryoimmunoglobulins are associated with numerous clinical problems ranging from collagen vascular disorders (rheumatoid arthritis and systemic lupus erythematosus) to infectious processes including HIV infection. The precise role of cryoglobulins in the pathophysiology of these disorders remains unresolved. Although cold insolubility may account for some of the observed processes, it cannot explain the entire array of findings in cryoglobulinemia. An alternative hypothesis suggests that the subtle differences responsible for cold precipitation of these proteins renders them intrinsically more sticky, resulting in deposition of cryoimmunoglobulins on vascular surfaces. We have explored this hypothesis by characterizing the binding of monoclonal cold soluble and cryoimmunoglobulins to silica beads as a model biological surface. It is found that monoclonal, type I, IgM and IgG cryoglobulins have only a slight tendency to bind to a greater extent to this surface than cold soluble immunoglobulins. Physical studies utilizing front surface fluorescence measurements and differential scanning calorimetry show surface interaction leads to partial thermal destabilization of the proteins. To a limited extent, this destabilization is more pronounced with the cryoglobulins compared to cold-soluble control homologues. Surface bound IgM cryoimmunoglobulin was also found to fix complement less efficiently than their cold soluble surface bound counterparts. These studies do not strongly support the hypothesis that pathological mechanisms of cryoimmunoglobulins primarily involve abnormal surface interactions, although surface effects could play a limited role in some situations.

The solubility of bovine lens crystallins.

Apparent thermodynamic parameters for the process of solubilization of the five major classes of bovine lens crystallins have been determined by the polyethylene glycol solubility method. Although each purified crystallin fraction displays significant structural heterogeneity as analyzed by high performance liquid chromatography, they behave as homogeneous proteins by the criteria of solubility. Using experimentally determined values for the apparent enthalpy and entropy of solution and the effects of a variety of low molecular weight solutes on crystallin solubility, the five classes can be arranged in order of the polarity of their solid phase intermolecular contacts as follows: gamma, high molecular weight beta greater than low molecular weight beta greater than high molecular weight alpha greater than alpha. Since alpha-crystallin is the major component of the insoluble material in bovine cataract, we suggest that cataract formation may be related to the intrinsic solubility and polarity of the lens crystallins.