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. 