Genetically determined deficiency of the third component of complement in the dog: In vitro studies on the complement system and complement-mediated serum activities

During the course of breeding a colony of Brittany spaniels, a number of dogs were found to have a genetically determined deficiency of the third component of complement (C3). The present studies were performed in order to characterize the C system and C-mediated serum activities in these C3-deficient dogs. By using a sensitive enzyme-linked immunoassay, C3-deficient dogs were found to have no more than 0.003% of the amount of antigenic C3 found in serum from normal dogs. Their levels of the other eight components of the classical pathway fell within the normal range with the exception of their C2 levels, which in three of the six deficient dogs were just below the range of normal. Their marked deficiency of C3 did not appear to be secondary to a serum inhibitor, because purified guinea pig C3 was able to fully restore hemolytic activity to the deficient dog serum. In addition, when deficient serum was added to either purified guinea pig C3 or normal dog serum, it failed to consume C3. In spite of their extremely low levels of immunoreactive C3, C3-deficient dogs had C3-like functional activity in their serum that was equivalent to 6 to 10% of the C3 titer in normal dog sera. The dose-response characteristics of the C3-like functional activity in the serum from deficient dogs was not linear, even in the initial portions of the curve. When C3 deficient serum was filtered through Sephacryl S-200, the peak of the C3-like functional activity was coincidental with the C3 functional activity in normal dog serum. Finally, affected dogs were found to be markedly deficient in serum opsonizing activity for the pneumococcus. In addition, the generation of chemotactic activity after zymosan activation of C3-deficient serum was also markedly deficient.