Structural polymorphism of the fourth component of human complement

Abstract

A B S T R A C T The fourth component of human complement (C4) in 102 individual plasma samples has been examined by the technique of antigen-antibody crossed electrophoresis (AACE). Electrophoretic heterogeneity of C4 was manifested by the repeated occurrence of seven different precipitin patterns. These patterns were formed by varying combinations of three subtypes of C4, differing in electrophoretic mobility. The subtypes were designated C, A, and A,, in order of increasing electrophoretic mobility toward the anode. The evidence that the observed electrophoretic heterogeneity of the C4 molecule represents structural polymorphism rests on five points: the pattern obtained from the plasma of a given individual was reproducible in different runs and with different bleedings; all seven patterns could be demonstrated on the same electrophoretic run; C4 of a given subtype retained its characteristic mobility after purification, when run alone or mixed with plasma containing C4 of other subtypes; the subtypes A, and C comprising pattern 6 could be separated chromatographically as well as electrophoretically; and the characteristic relative mobilities of different C4 subtypes, in plasma or after purification, were retained even after the rather large shift in mobility associated with conversion to C4i. The ratio of C4 hemolytic activity to protein concentration varied according to the subtype composition of individual samples, with highest ratios occurring with patterns composed of subtype C alone, intermediate values with patterns consisting of A and C, and lower values occurring with patterns containing subtype A alone. Although the mechanism of inheritance of this polymorphism is not yet clear, the data suggest that subtypes A and A, are inherited as autosomal codominant characteristics, independent of the inheritance of subtype C.Dr.

Genetic regulation of a structural polymorphism of human C3b receptor.

“…The structural polymorphism of the C3bR is unusual, because it can be detected by SDS-PAGE, whereas the demonstration of the polymorphic forms of the human serum complement proteins, C4, C2, C3, C6, C8, and factor B require procedures that separate proteins according to net charge rather than size (28)(29)(30)(31)(32)(33). Two forms of human C4 differing in their M, have been described, but they represent products of two separate loci, C4A and C4B (34).…”

The complement system in rheumatoid synovitis i. an analysis of complement component activities in rheumatoid synovial fluids

“…The experimental error of these component titrations is k l O~o . Antibody to purified C4 and to C3 was prepared as described (20,21) . A previously described method for radial immunodiffusion was used (22).…”

The Complement System in Rheumatoid Synovitis. II. Intracytoplasmic Inclusions of Immunoglobulins and Complement

“…Antisera to Clq were prepared by the method of Hanauer and Christian (14). Antisera to C4 protein and to C3 protein were prepared as described (15,16). Antisera to human serum albumin (HSA)* were made in rabbits.…”