Plasma Immunoreactive Pancreatic Cationic Trypsinogen in Cystic Fibrosis: a Sensitive Indicator of Exocrine Pancreatic Dysfunction

Abstract

SummaryPlasma immunoreactive cationic trypsin(ogen) levels were determined in 32 control subjects and 43 patients with varying degrees of pancreatic insufficiency including 35 with cystic fibrosis (CF) and eight with Shwachman's syndrome. In six CF infants less than 2 years of age, plasma trypsin(ogen) levels were significantly elevated (97.3 + 62.2 ng/ml) above the normal range for nine controls (7.0 + 5.9 ng/ml, P < 0.025). Four of these infants had steatorrhea, three of whom had undetectable duodenal trypsin activity after stimulation with secretin-cholecystokinin. In two CF infants, molecular size fractionation by gel filtration of plasma followed by radioimmunoassay of the column fractions demonstrated that trypsinogen was the only immunoreactive species in the circulation.In contrast, in older CF patients with steatorrhea (mean age, 15.3 + 4.6 years), plasma cationic trypsin(ogen) levels were undetectable or low (1.1 2 1.7 ng/ml). This finding clearly distinguished them from older CF patients without steatorrhea (mean age, 14.3 f 3.9 years) in whom cationic trypsin(ogen) levels were significantly higher (23.3 + 17.6 ng/ml; P < 0.01). The mean trypsin(ogen) concentration in the older CF patients without steatorrhea did not differ from the mean value for 23 normal subjects of similar age. Plasma cationic trypsin(ogen) levels in two Shwachman's patients with steatorrhea (0.19 and 0.86 ng/ml) were significantly lower than the values found in six Shwachman's patients without steatorrhea (5.9 + 2.3 ng/ml; P < 0.025). Furthermore, in nine older CF patients and eight Shwachman's patients, circulating trypsin(ogen) levels were highly correlated with duodenal trypsin output after secretin-cholecystokinin stimulation (r = 0.946, P < 0.01; r = 0.899, P < 0.01, respectively). These results suggest that in CF infants high levels of circulating trypsin(ogen) persist even in those with complete pancreatic insufficiency. In older CF patients and those with Shwachman's syndrome, however, circulating trypsin(ogen) accurately reflects residual pancreatic function.

Genetic and physiologic correlates of longitudinal immunoreactive trypsinogen decline in infants with cystic fibrosis identified through newborn screening

“…2 Children who have PS are known to have IRT levels that are elevated or within the normal range throughout childhood, corresponding to some functional pancreatic tissue. 2,17,18 Children who have severe disease have rapidly declining IRT levels, compared with the children with mild disease, and on average have IRT levels less than the lower limit of detection by 5 years of age, reflecting complete loss of pancreatic function. Our results confirm previous findings, and they show a different IRT decline model in infancy and childhood for the groups with mild and severe disease.…”

Serum Mucin-Associated Antigen Levels of Cystic Fibrosis Patients Are Related to Their Ages and Clinical Statuses

“…Unlike the pancreatic enzymes in CF patients' sera (23,(27)(28)(29), however, elevated serum mucin-associated antigen levels persisted among several adult C F patients (14). An elevated serum mucin-associated antigen level was reported in one adult CF without clinical evidence of pancreatic dysfunction (14).…”

Exclusion of linkage of Shwachman-Diamond syndrome to chromosome regions 6q and 12q implicated by a de novo translocation

“…Of the 13 multiplex families included for analysis (12 with 2 affected children and one with 3 affected children), none were known to involve consanguineous matings. Histories and cationic serum trysinogen measurements [Durie et al, 1981;Moore et al, 1986] supported the status of all relatives.…”