Separation of serum ciliary dyskinesia substances from cystic fibrosis subjects.

Purified serum immunoglobulin G (IgG), derived from eight cystic fibrosis (CF) and five carrier subjects, has been shown to be responsible for the mucociliary disturbances noted in the rabbit tracheal bioassay. A small molecular substance of less than 10,000 but greater than 1,000 daltons (by Amicon filtration) was found associated with gamma-globulin fractions isolated from sera of these same cystic patients and their parents. Once separated by PM-10 ultrafiltration, this small substance was unable to promote the ciliary dyskinesia response in eight of eight CF and five of five CF carrier individuals unless pooled purified human IgG was added. In addition, the IgG-rich fraction retained by PM-10 ultrafiltration was still able to promote the ciliary dyskinesia response in the bioassay, an event noted in our earlier work with whole serum. The size of the small serum substance and its association with IgG closely corresponds to that described for the oyster test system, as well as to that produced by cultured cells derived from homozygotes and heteroxygotes for this genetic disorder. The persistence of the ability to promote mucociliary disturbances by the IgG-rich retentate PM-10 fractions may be indicative of the ineffective molecular separation by the Amicon ultransfiltration apparatus or may represent another CF-related, IgG-associated substance not influenced by ultrafiltration. Speculation The genetic disturbance of CF can be explained by the presence of a molecule(s) which has an affinity for IgG, which in turn gives rise to the various physiologic facets of this disorder. This molecule(s) is present in CF only because of a deficiency of an enzyme which normally controls its level by inactivation.