Crystalline IgG protein in multiple myeloma: identification effects on coagulation and on lipoprotein metabolism.

Abstract

Abstract Plasma and serum of a patient with myeloma were found to contain a crystalline immunoglobulin protein, IgG of the Kappa type, MW (molecular weight) 158,200. Defects in coagulation were noted with delayed polymerization of fibrinogen and impaired platelet function. Protein-mediated anti-heparin activity could be shown in vivo and in vitro. Intravenous heparin (100 U. per kilogram) failed to prolong the patient's clotting time (6 minutes prior to injection, 9 minutes, 1 hour postinjection). A similar dose consistently prolonged clotting times of controls to at least 3 times the initial base line values. Using heparin 10 U. per kilogram, plasma postheparin lipolytic activity (PHLA) and monoglyceride hydrolase (MGH) were depressed below normal levels. Using high dose heparin (100 U. per kilogram) PHLA and MGH were elevated to 0.3 μEq per milliliter per minute and 3.57 mm. per milliliter per hour, normal range being, respectively, 0.5 to 0.75 and 9.3 to 13.1 on a similar dose of heparin. This heparin resistance was mediated by the patient's IgG. When heparin was preincubated with the patient's IgG, and the mixture then added to a rat adipose tissue lipase preparation, lipase activity was reduced from a control value of 42.2 μEq per free fatty acid per gram of wet tissue per hour to 9. Normal IgG showed no inhibitory effect. Interaction of heparin and IgG was tested directly by incubating 3 mg. of IgG with 1 unit of 3 H-heparin. Intact IgG bound 73 per cent of tritiated heparin, while normal IgG bound 20 per cent or less. The binding activity of the patient's IgG was apparently confined to the Fab portion of the molecule. The myeloma protein provides another example of antibody activity and a new specificity for myeloma proteins. Its crystalline structure makes it a unique protein for the study of immunoglobulin structure and antibody activity.