Abstract
An enzyme-linked immunosorbent assay, based on two monoclonal antibodies (Hreg1-1 and Hreg101-1) specific for pancreatic stone protein (PSP)/reg-protein, was developed to determine the concentration of this protein in serum from individuals with various diseases. The serum concentration of PSP/reg-protein was significantly higher in patients with various pancreatic diseases than in normal controls, and was also significantly higher in patients with acute pancreatitis or chronic relapsing pancreatitis than in patients with chronic pancreatitis. Furthermore, the serum PSP/reg-protein concentration was also significantly increased in liver cirrhosis, choledocholithiasis, and various cancers of the digestive system, and was extremely high in all patients tested with chronic renal failure. A significant correlation was apparent between the serum concentration of PSP/reg-protein and elastase-I in 68 patients with chronic pancreatitis or pancreatic cancer. Whereas only 7 of these patients showed a normal serum PSP/reg-protein concentration and a significantly increased elastase-I concentration, 15 of these patients showed a significantly increased serum PSP/reg-protein coecentration and a normal serum elastase-1 concentration. These results indicate that the serum PSP/reg-protein concentration may reflect pancreatic damage, especially in acute pancreatitis, and may be as sensitive a marker for such damage as elastase-I, although false positivity was apparent in renal failure and in some patients with hepatic dysfunction or digestive system malignancies.
Similar content being viewed by others
References
De Caro A, Lohse J, Sarles H. Characterization of protein isolated from pancreatic calculi of men suffering from chromic calcifying pancreatitis. Biochem Biophys Res Commun 1979; 87:1176–1182.
Multigner L, De Caro A, Lombardo D, et al. Pancreatic stone protein, a phosphoprotein which inhibits calcium carbonate precipitation from human pancreatic juice. Biochem Biophys Res Commun 1983;110:69–74.
De Caro A, Multigner L, Lafont H, et al. The molecular characteristics of a human pancreatic acidic phosphoprotein that inhibits calcium carbonate crystal growth. Biochem J 1984; 222:669–677.
Montalto G, Lusher M, De Caro A, et al. Analysis of human pancreatic juice constituents related to the pancreatic stone protein using monoclonal antibody. C R Acad Sci III 1985; 300:199–202.
Lechene de la Porte P, de Caro A, Lafont H, et al. Immuno-cytochemical localization of pancreatic stone protein in the human digestive tract. Pancreas 1986;1:301–308.
Montalto G, Bonicel J, Multigner L, et al. Partial amino acid sequence of human pancreatic stone protein, a novel pancreatic secretory protein. Biochem J 1986;238:227–232.
De Caro A, Bonicel J, Rouimi P, et al. Complete amino acid sequence of an immunoreactive form of human pancreatic stone protein isolated from pancreatic juice. Eur J Biochem 1987; 168:201–207.
Rouimi P, De Caro J, Bonicel J, et al. The disulfide bridges of the immunoreactive forms of human pancreatic stone protein isolated from pancreatic juice. FEBS Lett 1988;229:171–174.
De Caro A, Adrich Z, Fournet B, et al. N-terminal sequence extension in the glycosylated forms of human pancreatic stone protein. The 5-oxoproline N-terminal chain is O-glycosylated on the fifth amino acid residue. Biochim Biophys Acta 1989;994: 281–284.
Terazono K, Yamamoto H, Takasawa S, et al. A novel gene activated in regenerating islets. J Biol Chem 1988;263:2111–2114.
Terazono K, Watanabe T, Yonemura Y. A novel gene,reg, experssed in regenerating islets. In: Okamoto H (ed) Molecular biology of the islets of Langerhans. Cambridge: Cambridge University Press, 1990;301–313.
Terazono K, Uchiyama Y, Ide M, et al. Expression ofreg-protein in rat regenerating islets and its co-localization with insulin in the beta cell secretory granules. Diabetologia 1990; 33:250–252.
Watanabe T, Yonekura H, Terazono K, et al. Complete nucleotide sequence of humanreg gene and its expression in normal and tumoral tissues. J Biol Chem 1990;265:7432–7439.
Itoh T, Tsuzuki H, Katoh T, et al. Isolation and characterization of humanreg-protein produced inSaccharomyces cerevisiae. FEBS Lett 1990;272:85–88.
Gross J, Carlson RI, Brauer AW, et al. Isolation, characterization, and distribution of an unusual pancreatic human secretory protein. J Clin Invest 1985;76:2115–2126.
Satomura Y, Sawabu N, Ohta H, et al. The immunohistochemical evaluation of PSP/reg-protein in normal and diseased human pancreatic tissues. Int J Pancretol 1993;13:59–67.
Schmiegel W, Burchert M, Kalthoff H, et al. Immunochemical characterization and quantitaive distribution of pancreatic stone protein in sera and pancreatic secretions in pancreatic disorders. Gastroenterology 1990;99:1421–1430.
Hayakawa T, Kondo T, Shibata T, et al. Serum pancreatic stone protein in pancreatic diseases. Int J Pancreatol 1993;13: 97–103.
Galfre G, Milstein C. Preparation of monoclonal antibodies: Strategies and procedures. Methods Enzymol 1981;73:3–46.
Ishikawa E, Yoshitake S, Imagawa M. Preparation of monomeric Fab'-horseradish peroxidase conjugate using thiol groups in the hinge and its evaluation in enzyme immunoassay and immunohistochemical staining. Ann NY Acad Sci 1983;420: 74–89.
Committee for chronic pancreatitis of the Japanese Society of Gastroenterology. Clinical criteria for the diagnosis of chronic pancreatitis (in Japanese). Tokyo: Igaku Tosho, 1984.
Bernard JP, Adrich Z, Montalto G, et al. Inhibition of nucleation and crystal growth of calcium carbonate by human lithostathine. Gastroenterology. 1992;103:1277–1284.
Sarles H, Dagorn JC, Giorgi D, et al. Renaming pancretic stone protein as “lithostathine”. Gastroenterology 1990;99:900–901.
Orelle B, Keim V, Masciotra L, et al. Human pancreatitis-associated protein. Messenger RNA cloning and expression in pancreatic diseases. J Clin Invest 1992;90:2284–2229.
Multigner L, Sarles H, Lombardo D, et al. Pancreatic stone protein. II. Implication in stone formation during the course of chronic calcifying pancreatitis. Gastroenterology 1985;89: 387–391.
Giorgi D, Bernard JP, Rouquier S, et al. Secretory pancreatic stone protein messenger RNA. Nucleotide sequence and expression in chronic calcifying pancreatitis. J Clin Invest 1989;84: 100–106.
Gorelick FS, Adler G, Kern HF. Cerulein-induced pancreatitis. In: Go VLW, Dimagno ER, Gardner JD, Lebenthal E, Reber HA, Scheele GA (eds) The pancreas: Biology, pathology, and disease. 2nd ed. New York, Raven, 1993;501–526.
Marshall JS, Green AM, Pensky J, et al. Measurement of circulating desialylated glycoproteins and correlation with hepatocellular damage. J Clin Invest 1974;54:555–562.
Sawamura T, Kawasato S, Shiozaki Y, et al. Decrease of a hepatic binding protein specific for asialoglycoprotein with accumulation of serum asialoglycoproteins in galactosamine-treated rats. Gastroenterology 1981;81:527–534.
Borgstrom A, Ohlsson K. Studies on the turnover of endogenous cathodal trypsinogen in man. Eur J Clin Invest 1978;8: 379–382.
Ventrucci M, Rezzilli R, Gullo L, et al. Role of serum pancreatic enzyme assays in diagnosis of pancreatic disease. Dig Dis Sci 1989;34:39–45.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Satomura, Y., Sawabu, N., Mouri, I. et al. Measurement of serum PSP/reg-protein concentration in various diseases with a newly developed enzyme-linked immunosorbent assay. J Gastroenterol 30, 643–650 (1995). https://doi.org/10.1007/BF02367792
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF02367792