Gastroenterology

Gastroenterology

Volume 118, Issue 3, March 2000, Pages 573-581
Gastroenterology

Liver, Pancreas, and Biliary Tract
Autoimmune-related pancreatitis is associated with autoantibodies and a Th1/Th2-type cellular immune response,☆☆

https://doi.org/10.1016/S0016-5085(00)70264-2Get rights and content

Abstract

Background & Aims: Although autoimmunity may be involved in some cases of pancreatitis, the mechanism is still unknown. To clarify this, we studied serum autoantibodies, subsets of lymphocytes, and the Th1/Th2 balance of cellular immune responses in patients with autoimmune-related pancreatitis (AIP). Methods: Seventeen patients with AIP (8 men and 9 women; age, 53.2 ± 13.0 years) were studied. Autoantibodies including antilactoferrin (ALF) or carbonic anhydrase II antibody (ACA-II) were examined using the enzyme-linked immunosorbent assay (ELISA) or the indirect fluorescein antibody method. Intracellular cytokines (interferon gamma and interleukin 4) and subtypes of peripheral blood lymphocytes were examined by flow cytometry and ELISA. Results: More than one autoantibody was observed in all 17 patients. Serum antinuclear antibody was detected in 13 of 17 patients, ALF antibody in 13, ACA-II antibody in 10, rheumatoid factor in 5, and anti–smooth muscle antibody in 3, but antimitochondrial antibody in none. The serum levels of ACA-II and LF antibody were not correlated. HLA-DR+CD8+ and HLA-DR+CD4+ cells were significantly increased in peripheral blood (P < 0.05). CD4+ cells producing interferon gamma and the secreted levels were significantly increased compared with those in controls (P < 0.05), but interleukin 4 was not increased. Conclusions: An autoimmune mechanism against CA-II or LF, and Th1-type immune response, may be involved in AIP.

GASTROENTEROLOGY 2000;118:573-581

Section snippets

Subjects

Between 1987 and 1999, 24 of 313 patients with pancreatitis (11 men and 13 women) were diagnosed with AIP at the Kyoto University Hospital and satellite hospitals. In the present study, 17 patients (8 men and 9 women), who were prospectively diagnosed with AIP, were analyzed (Table 1). We diagnosed AIP as follows5, 6, 7, 8, 9, 10: (1) clinical symptoms associated with pancreatitis, (2) increased pancreatic enzyme or decreased pancreatic exocrine function, (3) increased serum gammaglobulin level

Autoantibodies

More than one autoantibody was detected in all 17 patients (Table 1). ANA was detected in 13 of 17 patients, ALF in 13, ACA-II in 10, RF in 5, and ASTHMA in 3. However, AMA was absent in all cases. Three patients without hypergammaglobulinemia had ACA-II or ALF (patients 3, 6, and 7). Two patients (patients 4 and 14) had neither ACA-II nor ALF. On the other hand, the patients with alcoholic or gallstone-related pancreatitis had no autoantibodies, except for ANA in 1 alcoholic patient (Table 2).

Discussion

Various pathophysiological hypotheses have been proposed for chronic pancreatitis.21, 22, 23, 24, 25, 26 Although alcohol and gallstone are common factors in the development of human pancreatitis, the underlying pathogenic mechanisms are still unclear. Recent observations suggest a functional role of T lymphocytes, such as cytotoxicity27 or the neuroimmune interactions in human pancreatitis.28 Chronic pancreatitis sometimes coexists with SjS, PSC, or PBC,11, 12, 13, 14, 15 which suggests the

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    Supported by a Grant-in-Aid for Scientific Research (C) of the Ministry of Culture and Science of Japan (11670495); a Grant-in-Aid for the “Research for the Future” Program from The Japan Society for Promotion of Science (JSPS-RFTF97I00201); and Supporting Research Funds from The Japanese Foundation for Research and Promotion of Endoscopy (JFE-1997).

    ☆☆

    Address requests for reprints to: Kazuichi Okazaki, M.D., Ph.D., Department of Gastroenterology and Endoscopic Medicine, Kyoto University Hospital, Shogoin-Kawaracho, Sakyo, Kyoto, 606-8507, Japan. e-mail: [email protected]; fax: (81)-75-751-3414.

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