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. 1993 Oct;34(10):1452–1457. doi: 10.1136/gut.34.10.1452

Expression of major histocompatibility antigens in human chronic pancreatitis.

R P Jalleh 1, J A Gilbertson 1, R C Williamson 1, S D Slater 1, C S Foster 1
PMCID: PMC1374561  PMID: 8244120

Abstract

T-lymphocytic infiltration of the exocrine pancreas and liver in patients with chronic pancreatitis has suggested that cell mediated immune mechanisms may play a part in the pathogenesis of this disease. As expression of major histocompatibility (MHC) antigens is a prerequisite for organ specific autoimmunity, the expression of HLA class I (beta 2-microglobulin) and class II (HLA-DR) determinants have been analysed, together with the presence of T-lymphocytes, in 93 patients (64 men and 29 women, mean age 40.6 years) having an operation for chronic pancreatitis. Ethanol (63 patients), recurrent acute pancreatitis (12), congenital lesions (2), and unknown (16) were suggested to be the causes of the disease. Immunohistochemical staining of formalin fixed and paraffin wax embedded tissue sections used conventional immunohistochemical techniques with specific anti-serum samples. No MHC expression was identified in 10 histologically normal pancreatic control specimens or in four cases of chronic pancreatitis secondary to obstruction by neuroendocrine tumours within the head of the pancreas. beta 2-microglobulin expression by pancreatic exocrine epithelial cells was seen in 76 chronic pancreatitis specimens (82%) while HLA-DR was present in 61 (66%). Simultaneous expression of both class I and II determinants was seen in 53 (57%) of cases. MHC determinant expression was not found in 10 cases (11%) of chronic pancreatitis. In the positive specimens, expression was confined to ductal and ductular (interlobular and intralobular) epithelium with no staining of acinar cells. Staining was not related to the suspected cause of the disease or age. T-lymphocytes were more prominent in chronic pancreatitis mean (SEM) (131 (15) cells per high powered field) than controls (5 (1), p < 0.01). Aberrant MHC expression by exocrine pancreatic epithelial cells occurring in the presence of an appreciable T-cell infiltration confirmed that the appropriate cellular conditions were present for cell mediated cytotoxicity to contribute to the pathogenesis of chronic pancreatitis.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Ballardini G., Mirakian R., Bianchi F. B., Pisi E., Doniach D., Bottazzo G. F. Aberrant expression of HLA-DR antigens on bileduct epithelium in primary biliary cirrhosis: relevance to pathogenesis. Lancet. 1984 Nov 3;2(8410):1009–1013. doi: 10.1016/s0140-6736(84)91108-5. [DOI] [PubMed] [Google Scholar]
  2. Basham T. Y., Merigan T. C. Recombinant interferon-gamma increases HLA-DR synthesis and expression. J Immunol. 1983 Apr;130(4):1492–1494. [PubMed] [Google Scholar]
  3. Bedossa P., Bacci J., Lemaigre G., Martin E. Lymphocyte subsets and HLA-DR expression in normal pancreas and chronic pancreatitis. Pancreas. 1990 Jul;5(4):415–420. doi: 10.1097/00006676-199007000-00007. [DOI] [PubMed] [Google Scholar]
  4. Bell J. I., Todd J. A., McDevitt H. O. The molecular basis of HLA-disease association. Adv Hum Genet. 1989;18:1–41. [PubMed] [Google Scholar]
  5. Bottazzo G. F., Pujol-Borrell R., Hanafusa T., Feldmann M. Role of aberrant HLA-DR expression and antigen presentation in induction of endocrine autoimmunity. Lancet. 1983 Nov 12;2(8359):1115–1119. doi: 10.1016/s0140-6736(83)90629-3. [DOI] [PubMed] [Google Scholar]
  6. Bovo P., Mirakian R., Merigo F., Angelini G., Cavallini G., Rizzini P., Bottazzo G. F., Scuro L. A. HLA molecule expression on chronic pancreatitis specimens: is there a role for autoimmunity? A preliminary study. Pancreas. 1987;2(3):350–356. doi: 10.1097/00006676-198705000-00016. [DOI] [PubMed] [Google Scholar]
  7. Daar A. S., Fuggle S. V., Fabre J. W., Ting A., Morris P. J. The detailed distribution of HLA-A, B, C antigens in normal human organs. Transplantation. 1984 Sep;38(3):287–292. doi: 10.1097/00007890-198409000-00018. [DOI] [PubMed] [Google Scholar]
  8. Dani R., Antunes L. J., Ribeiro J. E., Nogueira C. E., Ribeiro T. Immunological participation in chronic calcifying pancreatitis. Digestion. 1974;11(5-6):333–337. doi: 10.1159/000197600. [DOI] [PubMed] [Google Scholar]
  9. David-Watine B., Israël A., Kourilsky P. The regulation and expression of MHC class I genes. Immunol Today. 1990 Aug;11(8):286–292. doi: 10.1016/0167-5699(90)90114-o. [DOI] [PubMed] [Google Scholar]
  10. Foulis A. K. C. L. Oakley lecture (1987). The pathogenesis of beta cell destruction in type I (insulin-dependent) diabetes mellitus. J Pathol. 1987 Jul;152(3):141–148. doi: 10.1002/path.1711520302. [DOI] [PubMed] [Google Scholar]
  11. Guy O., Robles-Diaz G., Adrich Z., Sahel J., Sarles H. Protein content of precipitates present in pancreatic juice of alcoholic subjects and patients with chronic calcifying pancreatitis. Gastroenterology. 1983 Jan;84(1):102–107. [PubMed] [Google Scholar]
  12. Haboubi N. Y., Ali H. H., Braganza J. M. Altered liver histology in patients with pancreatitis: a clue to etiology? Mt Sinai J Med. 1986 May;53(5):380–388. [PubMed] [Google Scholar]
  13. Hsu S. M., Raine L., Fanger H. Use of avidin-biotin-peroxidase complex (ABC) in immunoperoxidase techniques: a comparison between ABC and unlabeled antibody (PAP) procedures. J Histochem Cytochem. 1981 Apr;29(4):577–580. doi: 10.1177/29.4.6166661. [DOI] [PubMed] [Google Scholar]
  14. Italian immunology: a reply. Immunol Today. 1989 Apr;10(4):114–115. doi: 10.1016/0167-5699(89)90239-9. [DOI] [PubMed] [Google Scholar]
  15. Jalleh R. P., Gilbertson J. A., Williamson R. C., Foster C. S. Morphological and immunohistochemical analysis of the human liver in chronic pancreatitis. Gut. 1991 Nov;32(11):1386–1391. doi: 10.1136/gut.32.11.1386. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Kakizaki G., Sasahara M., Aikawa T., Matsuo M., Sugawara Y., Nakamura K., Endo S., Ito Y. On the pathogenesis of chronic alcoholic pancreatitis from the viewpoint of experimental results in rats. Int J Pancreatol. 1987 Apr;2(2):101–116. doi: 10.1007/BF03015003. [DOI] [PubMed] [Google Scholar]
  17. Khoury E. L., Greenspan J. S., Greenspan F. S. Adrenocortical cells of the zona reticularis normally express HLA-DR antigenic determinants. Am J Pathol. 1987 Jun;127(3):580–591. [PMC free article] [PubMed] [Google Scholar]
  18. Klöppel G., Maillet B. Chronic pancreatitis: evolution of the disease. Hepatogastroenterology. 1991 Oct;38(5):408–412. [PubMed] [Google Scholar]
  19. Klöppel G., Maillet B. Pseudocysts in chronic pancreatitis: a morphological analysis of 57 resection specimens and 9 autopsy pancreata. Pancreas. 1991 May;6(3):266–274. [PubMed] [Google Scholar]
  20. Lankisch P. G., Koop H., Seelig R., Seelig H. P. Antinuclear and pancreatic acinar cell antibodies in pancreatic diseases. Digestion. 1981;21(2):65–68. doi: 10.1159/000198543. [DOI] [PubMed] [Google Scholar]
  21. Lautenschlager I., Inkinen K., Taskinen E., Charles M. A., Hayry P. Major histocompatibility complex protein expression on pancreas and pancreatic islet endocrine cell subsets. Am J Pathol. 1989 Dec;135(6):1129–1137. [PMC free article] [PubMed] [Google Scholar]
  22. Lendrum R., Walker G. Serum antibodies in human pancreatic disease. Gut. 1975 May;16(5):365–371. [PMC free article] [PubMed] [Google Scholar]
  23. Monaco J. J., Cho S., Attaya M. Transport protein genes in the murine MHC: possible implications for antigen processing. Science. 1990 Dec 21;250(4988):1723–1726. doi: 10.1126/science.2270487. [DOI] [PubMed] [Google Scholar]
  24. Nerenberg S. T., Prasad R., Pedersen L. D., Biskup N. S. Radioimmunoassay for detection of latent chronic alcoholic pancreatitis, an unrecognized clinical syndrome. Clin Chem. 1980 Feb;26(2):214–218. [PubMed] [Google Scholar]
  25. Noronha M., Bordalo O., Dreiling D. A. Alcohol and the pancreas. II. Pancreatic morphology of advanced alcoholic pancreatitis. Am J Gastroenterol. 1981 Aug;76(2):120–124. [PubMed] [Google Scholar]
  26. Payan H., Sarles H., Demirdjian M., Gauthier A. P., Cros R. C., Durbec J. P. Study of the histological features of chronic pancreatitis by correspondence analysis. Identification of chronic calcifying pancreatitis as an entity. Rev Eur Etud Clin Biol. 1972 Aug-Sep;17(7):663–670. [PubMed] [Google Scholar]
  27. Rumessen J. J., Marner B., Pedersen N. T., Permin H. Autoantibodies in chronic pancreatitis. Scand J Gastroenterol. 1985 Oct;20(8):966–970. doi: 10.3109/00365528509088856. [DOI] [PubMed] [Google Scholar]
  28. Sarles H., Bernard J. P., Gullo L. Pathogenesis of chronic pancreatitis. Gut. 1990 Jun;31(6):629–632. doi: 10.1136/gut.31.6.629. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Sarles H. Chronic calcifying pancreatitis--chronic alcoholic pancreatitis. Gastroenterology. 1974 Apr;66(4):604–616. [PubMed] [Google Scholar]
  30. Sarles H., Sarles J. C., Camatte R., Muratore R., Gaini M., Guien C., Pastor J., Le Roy F. Observations on 205 confirmed cases of acute pancreatitis, recurring pancreatitis, and chronic pancreatitis. Gut. 1965 Dec;6(6):545–559. doi: 10.1136/gut.6.6.545. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Sarner M., Cotton P. B. Classification of pancreatitis. Gut. 1984 Jul;25(7):756–759. doi: 10.1136/gut.25.7.756. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Schütt C., Friemel H., Schulze H. A., Zubaidi G. Specific lymphocyte sensitization in chronic pancreatitis. Digestion. 1975;13(5):308–311. doi: 10.1159/000197723. [DOI] [PubMed] [Google Scholar]
  33. Singh S. M., Reber H. A. The pathology of chronic pancreatitis. World J Surg. 1990 Jan-Feb;14(1):2–10. doi: 10.1007/BF01670538. [DOI] [PubMed] [Google Scholar]
  34. Spencer J., Pugh S., Isaacson P. G. HLA-D region antigen expression on stomach epithelium in absence of autoantibodies. Lancet. 1986 Oct 25;2(8513):983–983. doi: 10.1016/s0140-6736(86)90638-0. [DOI] [PubMed] [Google Scholar]
  35. Suda K., Mogaki M., Oyama T., Matsumoto Y. Histopathologic and immunohistochemical studies on alcoholic pancreatitis and chronic obstructive pancreatitis: special emphasis on ductal obstruction and genesis of pancreatitis. Am J Gastroenterol. 1990 Mar;85(3):271–276. [PubMed] [Google Scholar]
  36. THAL A. P., MURRAY M. J., EGNER W. Isoantibody formation in chronic pancreatic disease. Lancet. 1959 May 30;1(7083):1128–1129. doi: 10.1016/s0140-6736(59)90711-1. [DOI] [PubMed] [Google Scholar]
  37. Thorsgaard Pedersen N., Nyboe Andersen B., Pedersen G., Worning H. Chronic pancreatitis in Copenhagen. A retrospective study of 64 consecutive patients. Scand J Gastroenterol. 1982 Oct;17(7):925–931. doi: 10.3109/00365528209181116. [DOI] [PubMed] [Google Scholar]
  38. Uys C. J., Bank S., Marks I. N. The pathology of chronic pancreatitis in Cape Town. Digestion. 1973;9(5):454–468. doi: 10.1159/000197474. [DOI] [PubMed] [Google Scholar]
  39. Wan Y. J., Orrison B. M., Lieberman R., Lazarovici P., Ozato K. Induction of major histocompatibility class I antigens by interferons in undifferentiated F9 cells. J Cell Physiol. 1987 Feb;130(2):276–283. doi: 10.1002/jcp.1041300214. [DOI] [PubMed] [Google Scholar]

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