Abnormal serum factor in patients with cystic fibrosis of the pancreas.

Abstract

Extract: Serum from patients with cystic fibrosis of the pancreas (CFP) was found to disorganize the ciliary rhythm in explants of respiratory epithelium. This serum factor was present in all 75 patients with CFP and absent from the serum of 75 other patients having a variety of diseases with clinical features similar to those seen in CFP. The bio-assay method to detect the disorganized ciliary beat was performed in the following manner. Specimens of rabbit tracheal mucosa were placed and maintained in tissue culture flasks using standard tissue culture technique. After 4–6 days of incubation, specimens with beating cilia were removed from the flasks, placed on glass slides, exposed to a drop of test serum, covered with a sealed coverslip, and observed at room temperature with a magnification of 550 using phase contract illumination. A disorganized beat was usually observed within 5–10 minutes and persisted for a period of up to one hour. The serum factor was found to be heat labile, nondialysable, and precipitated with the euglobulins. Ghromatographic examination of serum from a patient with CFP on a column of Sephadex G-200 showed that the serum factor was eluted with the macroglobulin fraction as well as between the gamma globulin and albumin peaks. The serum factor was also detected in the parents of children with cystic fibrosis; however, the concentration of the factor appeared lower. The native sera from parents produced a disorganized beat in 7 of 25 cases. Upon concentrating the euglobulin fraction 2.5:1, the factor was detected in the remaining 18 sera. Similar concentration of sera from control patients resulted in only one positive reaction in the 25 sera tested. In addition, a ten-fold concentration of euglobulin from normal controls failed to disorganize the ciliary beat. Speculation: Although the mode of action of the serum factor has not been determined, the macromolecules in the serum may alter transport of electrolytes, thereby producing changes in the action potential within the cell and resulting in a disorganized ciliary beat. This postulate may have also some relation to the pathogenesis of the disease in view of the recent observation by MANGOS and MCSHERRY [7] that saliva of patients with CFP inhibits sodium transport.