Ciliary dyskinesia factors in cystic fibrosis and asthma.

Abstract

CYSTIC fibrosis (CF) homozygotes and heterozygotes carriers for CF harbour a factor in their serum (termed CDF) which causes ciliary dyskinesia when applied to ciliated epithelial tissue derived from rabbit trachea1–4. Spock et al.1 reported that serum ciliary dyskinesia activity (CDA) was a specific marker for the CF gene. Conover et al.5 have reported that a CDA is also found in sera from individuals with various respiratory and autoimmune disorders; they have since suggested that the CF-ciliary dyskinesia factor was C3a (anaphylatoxin), and proposed that a defect or deficiency in the anaphylatoxin inactivator was the primary gene defect in cystic fibrosis6,7. Other laboratories have been unable to detect CF-CDF using a rabbit tracheal bioassay for the detection of the CF-CDF (refs 8–10). Using a modified rabbit tracheal bioassay, we have confirmed that serum from individuals with bronchial asthma and serum from homozygotes and heterozygotes for CF cause ciliary dyskinesia, whereas normal healthy control sera do not. Most individuals with asthma, however, were also found to have serum which causes a subsequent ciliostasis. All sera tested by bioassay for CFP by electrofocusing indicated that all CDA-positive sera except sera from seven of eight individuals with asthma were also positive for cystic fibrosis protein (CFP). The CFP is a small (molecular weight 5,000–9,000), positively charged compound and is found in sera from most homozygotes and heterozygotes for CF (refs 11–16). These two findings suggested that the CDAs in CF sera and in asthmatic sera could be due to two different substances. We have developed two simple chromatographic techniques which can separate CDAs in CF and asthmatic sera. Our results indicate that they may be useful in purifying a CF-specific CDA. Purification of this CF-CDA is a prerequisite for its biochemical characterisation and for elucidating its role in the pathophysiology of CF (ref. 17).