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Immunoreactive pancreatic Reg protein in sera from cystic fibrosis patients with and without pancreatic insufficiency

BACKGROUND The biological function of the Reg protein, a non-enzymic protein produced in fairly large amounts by pancreatic acinar cells, remains elusive. Its susceptibility to proteolysis leading to precipitation of the proteolysis product at neutral pH suggests that it could contribute to the protein plugging observed in cystic fibrosis (CF). AIMS To study its behaviour in the serum of CF patients with or without pancreatic insufficiency and to compare it with that of other pancreatic secretory proteins. PATIENTS 170 patients (93 with CF, 55 controls, and 22 with chronic pancreatitis) were studied. METHODS Reg protein was measured using a specific enzyme immunoassay and its molecular form in CF sera was characterised by gel filtration. Molecular gene expression was investigated by dot-blot hybridisation. RESULTS Reg protein was present in all CF sera studied from patients with or without pancreatic insufficiency, and in all cases the level was significantly higher than in controls. Its chromatographic behaviour in CF sera was identical with that of the protein present in normal serum. No correlation was found between the levels of Reg protein and trypsin(ogen) (or lipase) in CF, nor in control sera or normal pancreatic juice. Molecular gene expression of the corresponding proteins investigated in pancreatic tissues showed an absence of correlation between the mRNA levels. CONCLUSIONS Reg protein may not be a secretory exocrine protein like the digestive enzymes but rather a hormone-like secretory substance with an endocrine or paracrine function.