Malcolm R. Mackenzie

The hyperviscosity syndrome: I. In IgG myeloma. The role of protein concentration and molecular shape

The hyperviscosity syndrome is an uncommon complication in IgG myeloma. Its occurrence has been ascribed to the presence in the serum of high molecular weight polymers of the IgG proteins. Three patients with IgG myeloma and the clinical hyperviscosity syndrome were investigated, none of whom had IgG polymers in the serum by analytical ultracentrifugation. Relative serum viscosity in these patients ranged from 10 to 17.4 (normal 1.4-1.8). The total serum proteins ranged from 14 to 19 g/100 ml of which 10 to 17 g/100 ml was IgG globulin. Physicochemical studies of two of the isolated myeloma proteins indicated that they were of normal molecular weight (near 158,000 and 162,000). Protein Ca had a normal molecular radius (52.2 A) and configuration, (intrinsic viscosity of 5.5 cc/g, frictional ratio 1.48), but was present in very high concentration in the serum. Protein Pur had an increased molecular radius (58.2 A) and was asymmetrical (intrinsic viscosity 10.2 cc/g, frictional ratio 1.63). These results indicate that the concentration and molecular configuration of the myeloma protein are important determinants of the presence or absence of the hyperviscosity syndrome.

Human antibodies to human IgA globulins

Abstract Human antibodies to IgA globulin have been demonstrated in human sera by a passive hemagglutination method using as antigens IgA myeloma proteins coupled to inert indicator red cells. The vast majority of sera containing such agglutinators occur in patients with little or no serum IgA and normal levels of IgG and/or IgM. Specificity of the antibodies was shown by inhibition of agglutination. The antibodies of different sera appear directed toward different antigenic sites in the alpha chains. Such sera may prove useful in demonstrating allotypic genetically determined antigens in IgA molecules analogous to the Gm factors of IgG molecules.

Synthesis of macroglobulins in vitro.

THE increased concentration of macroglobulin (IgM) in the sera of patients with macroglobulmaemia is usually ascribed to excessive production of the protein by neoplastic cells of the lymphocytic series. This inference is based on, two observations: the association of increased concentrations of IgM and abnormal “lymphocytoid” or “plasmacytoid” cells, and the staining of these cells by fluorescein-labelled antibody to IgM (ref. 1). Recently, a patient (J. P.) with γ-macroglobulinaemia and circulating lymphosarcoma cells (leucolymphosarcoma) offered a rare opportunity to examine directly the capacity of these cells to synthesize IgM. For comparison, the synthesis of IgM by leucocytes of a normal subject and of patients with various haematological diseases was also investigated. In additional experiments, the synthesis of ribonucleic acid (RNA) by the lymphosarcoma cells and certain other leucocytes was investigated.