Studies on ciliary dyskinesia factor in cystic fibrosis. I. Bioassay and heterozygote detection in serum

We have modified Spock’s rabbit tracheal bioassay to the extent that it is reproducible and reliable for the detection of the cystic fibrosis (CF) gene in single or double dose from serum. Three critical modifications were: (1) maintaining a 37°C temperature throughout screening and bioassay, (2) setting high standards of tissue selection to be used for bioassay, (3) quick manipulations during the bioassay. These alterations have eliminated the necessity of concentrating euglobulins from sera of CF carriers in order to detect a ciliary dyskinesia factor (CDF). In addition, the time necessary to detect a CDF response was reduced to 3 to 6 minutes in every serum sample from CF homozygotes and obligate heterozygotes. In general, sera from metachromasia negative CF affected and carrier subjects elicited a ciliotoxic response, as opposed to the more commonly observed ciliary dyskinesia seen in metachromasia positive CF individuals and their parents. Speculation: CDF is a manifestation of a normal cellular product which is a small molecule bound to IgG. The resulting complex represents the CDF detected by bioassay. The defect in CF is in the production or release of a factor inhibiting the CDF.