Restoration by purified C3b inactivator of complement-mediated function in vivo in a patient with C3b inactivator deficiency

Abstract

In a patient with lifelong increased susceptibility to infection and multiple abnormalities in complement-mediated functions, the infusion of normal plasma had been seen to produce a prolonged partial correction of serum abnormalities. It was subsequently shown that the patient was genetically deficient in the C3b inactivator and that immunochemical depletion of C3b inactivator from normal serum resulted in abnormalities similar to those found in the patient's serum, including alternative pathway C3 activation. Highly purified C3b inactivator was obtained from the euglobulin fraction of normal human serum, sterilized by filtration, and infused intravenously. Partial or complete correction of almost all the known serum abnormalities was obtained. C3b almost disappeared from the serum within 4-5 h, as did Factor C activity. Native C3, C5, and serum hemolytic activity rose to normal or near-normal levels over 4 days and were sustained for another week. Factor B, properdin, opsonic activity, and bactericidal activity reached a level at least two-five times that found before the infusion within 24 h and fell over the next 5 days. These observations prove the primary role of C3b inactivator deficiency in the patient's disease and demonstrate clearly the curcial role in vivo of C3b inactivator in modulating alternative pathway activity.