Studies on ciliary dyskinesia factor in cystic fibrosis. IV. Its possible identification as anaphylatoxin (C3a)-IgG complex

Presumptive evidence indicates that the substance responsible for the pathophysiologic conditions of cystic fibrosis (CF) is a complement component, C3a, also known as anaphylatoxin. The known biochemical and physiological properties of C3a, together with the behavior of this purified substance when associated with IgG in our tracheal bioassay, compare favorably with those of molecular species which we have separated from sera and cell cultures of CF homozygotes and heterozygotes. Sera from normal healthy subjects, previously inactive by bioassay for ciliary dyskinesia factor (CDF), were converted to a CDF positive state by incubation with epsilon-amino-caproic-acid (EACA). EACA is a known inhibitor of the carboxypeptidase-B-like anaphylatoxin inactivator, and is the methof of choice for accumulating anaphylatoxins in normal blood. Incubation of EACA-treated normal sera and two fresh CDF-positive CF sera with carboxypeptidase-B produced reversion in all instances to a CDF negative, normal state. It is proposed that anaphylatoxin inactivator, a carboxypeptidase-B-like enzyme, is defective or deficient in cystic fibrosis and that this deficiency is the primary gene defect.