Quantitative relationships of the fourth complement component in human cerebrospinal fluid.

A technique for the measurement of cerebrospinal fluid C4 concentration in unconcentrated specimens has been developed with the methods of electroimmunodiffusion and immunofixation. The method has proved to be reproducible and requires only microliter volumes of undiluted cerebrospinal fluid (CSF). The mean value for CSF C4 concentrations in 16 neurologically normal individuals was 325 +/- 32 mug/100 ml. A positive correlation between CSF C4 concentration and the concentration of CSF albumin and total protein was observed. The positive correlation between the concentrations of CSF C4 and albumin was, however, more clearly defined than the relationship of CSF C4 to total CSF protein.

Plasma exchange for cold agglutinin hemolytic anemia.

Two patients with advanced lymphoma, chronic cold agglutinin disease refractory to conventional therapy and severe, progressive anemia were treated with exchange plasma transfusion. Both experienced significant reduction in titers. The first patient, in whom the procedure was done manually, died with widespread lymphoma without achieving apparent clinical benefit. The second patient was exchanged using the Aminco Celltrifuge, with improvement in in vitro compatibility tests and transfusion tolerance. The technical details of continuous-flow centrifugation exchange plasma transfusion are described.

Waldenström's macroglobulinemia and neuropathy. Deposition of M-component on myelin sheaths.

Chronic idiopathic polyneuropathy of a primary demyelinating type developed in a man who had had recurrent herpes simplex 2 for 10 years. A serum IgM kappa M-component was demonstrated on the myelin of individual sural nerve fibers by direct immunofluorescence microscopy. Marrow lymphocytosis and serum M-component increased with time. Attempts to confirm antibody activity of the M-component were negative. The evidence suggests that the attachment of M-component to nerve is a physical-chemical one. Interaction of M-component and nerve appears to have led to the neuropathy as an early manifestation of Waldenström's macroglobulinemia.

Inherited deficiency of the third component of human complement (C'3).

A kindred has been investigated in which seven individuals were found to have half-normal serum concentrations of the third component of complement (C'3). This partial deficiency was transmitted as an autosomal dominant trait. Affected individuals were entirely healthy. Hemolytic complement titers were slightly reduced but immune adherence titers and reagent titrations of the classical complement components were normal.Examination for C'3 allotypes revealed that all affected individuals had patterns resembling those of homozygotes. Analysis of the inheritance of C'3 structural genes disclosed that the most likely mechanism for partial C'3 deficiency in this family was nonexpression of one allele.

C'3 synthesis in the human fetus and lack of transplacental passage.

Allotypic differences in the third component of complement between mothers and their newborns provided evidence for synthesis of this complement component by the fetus. There was no indication that this protein traversed the placenta. The known low level of C'3 in the neonate was confirmed, and the maternal concentration was found to be significantly elevated.

Genetic polymorphism of the third component of human complement (C'3).

Polymorphism of human C'3 has been defined by prolonged agarose electrophoresis of fresh serum. At least four, and probably five, alleles have been identified by the electrophoretic mobilities of gene products. Inheritance of three alleles, F(1) F, and S, is consistent with the autosomal condominant type. The inheritance of S(1) is probably codominant and that of F(0.8) is not known. Of the 15 phenotypes predicted by these alleles, eight have been observed. The allotypes appear to differ in net surface charge at pH 8.6, but show no obvious differences in complement activity, in molecular size, or in binding of Ca(++). The concentrations of the two gene products in serum from all known heterozygotes are approximately equal. The S gene is most common in the three major races of man. The F gene is relatively common in Caucasians, less common in American Negroes, and relatively uncommon in Orientals.