Deficiency of Hemolytic C1 in Experimental Hypogammaglobulinemia

It has been known for many years that agammaglobulinemic patients tend to have deficient C1 activity, paralleled by a reduced level of C1q protein. The only complete experimental analogue of X-linked recessive agammaglobulinemia is achieved in the chicken. Total hemolytic C was titered in such chickens by Gewurz and Cooper several years ago, but to our knowledge no one has looked at their C1. A major obstacle has been the inadequacy of mammalian hemolysins in total C assays, thus almost assuring that a conventional EAC 4 cell would be inadequate. We found, however, that such a cell yields a linear dose-response with chicken serum, but felt we had to examine this paradox before titering sera of hypogammaglobulinemic chickens. Rabbit hemolysin fixes chicken C but probably does not activate it to any extent. In higher dilution, in low ionic strength buffer, we believe that C1 is activated, and that it is largely activated C1 which is assayed with a standard EAC 4 .