BINDING OF I125 LABELED PROTEINASES TO PLASMA-PROTEINS IN CYSTIC-FIBROSIS

Samples of plasma or serum from 53 cystic fibrosis (CF) patients, 90 relatives of CF patients, and 159 controls have been incubated with porcine or bovine 125I-trypsin, electrophoresed on polyacrylamide gel, and autoradiographed. In these individuals, the main binding protein for125I-trypsin has been shown to be α2- macroglobulin (α2M). Using this method of analysis, no difference in electrophoretic migration of125I-trypsin- α2M complexes has been observed between CF and control individuals. However, trypsin binding to IgG has been observed in 80% of CF patients, 30% of their mothers, 3% of controls, and in two patients affected with pancreatitis. These trypsin binding immunoglobulins are called Tblg, and specifically, TblgG when referring to the G class. Experimental evidence indicates that binding of trypsin to IgG occurs through the Fab portion of the molecule. TblgG must be antibodies most probably induced by the exogenous trypsin ingested daily by most CF patients (and by patients affected with chronic pancreatitis). Antibodies against porcine pancreatic elastase have been observed using the same analysis, but not as frequently as Tblg. Speculation Antibodies against trypsin are known to have an inhibitory capacity on its enzymatic activity: is Tblg responsible, at least in part, for the decrease in arginine esterase activity observed by some authors in plasma of CF patients and of some heterozygotes?. The presence of TblgG in CF patients raises again the interesting question of an autoimmune process in CF, directed not only against structural pancreatic proteins but also against human pancreatic enzymes. © 1979 International Pediatric Research Foundation, Inc.