Studies on cystic fibrosis using isoelectric focusing. III. Correlation between cystic fibrosis protein and ciliary dyskinesia activity in serum shown by a modified rabbit tracheal bioassay.

We have developed a modified rabbit tracheal bioassay for use in investigating 
a possible correlation between cystic fibrosis protein (CFP) and ciliary dyskinesia 
factor (CDF) in human serum. The bioassay requires high standards of 
tissue selection, and all epithelial tissue must be free of underlying 
connective tissue. When serum samples were collected and processed carefully and 
warmed to 37 degrees before assay, CDF could be reliably detected 
in 31 of 31 sera from cystic fibrosis (CF) homozygotes or 
obligate heterozygotes in 35 min or less without prior fractionation or 
concentration of sera, whereas 13 of 14 normal control sera were 
nonreactive. CDF-positive serum reacts in three consecutive phases: (1) initial increase 
in ciliary beat frequency, (2) ciliary dyskinesia, and (3) tissue destruction 
with extrusion of single ciliated cells, mucus, and debris. Our results 
confirm the association of CDF with cystic fibrosis. The bioassay is 
not specific for CF, however, when whole sera are bioassayed, since 
serum from several patients with bronchial asthma also caused ciliary dyskinesia. 
However, this finding need not preclude using rabbit tracheal ciliated epithelial 
tissue as an assay for following the purification of CDF. Isoelectric 
focusing showed that the presence or absence of CFP corresponded with 
that of dyskinesia activity in all sera tested except for the 
active samples from seven asthma patients, which were negative for CFP. 
The results indicate that CFP and CDF may be identical or 
closely related markers for the CF gene, and suggest that the 
activity detected by the rabbit tracheal bioassay in sera from patients 
with asthma and other diseases probably is caused by a substance 
different from a CF- specific CDF. 