Autoimmune-related pancreatitis is associated with autoantibodies and a Th1/Th2-type cellular immune response

Okazaki, Kazuichi; Uchida, Kazushige; Ohana, Masaya; Nakase, Hiroshi; Uose, Suguru; Inai, Maki; Matsushima, Yumi; Katamura, Kenji; Ohmori, Katsuyuki; Chiba, Tsutomu

doi:10.1016/s0016-5085(00)70264-2

Cited by 506 publications

(394 citation statements)

References 39 publications

Supporting

Mentioning

353

Contrasting

Unclassified

Order By: Relevance

“…16 Elevations of lactoferrin have previously been reported in the pancreatic juice of patients with chronic calcifying pancreatitis and/or autoimmunerelated pancreatitis. [17][18][19][20] Interestingly, in experimental studies, lactoferrin has been shown to inhibit the growth of some solid tumors such as colon, esophagus, and lung tumors. 21,22 Interestingly, stool lactoferrin has been shown to be a sensitive marker of intestinal inflammation in patients with intestinal tract symptoms and is being used in clinical practice to identify patients with intestinal tract inflammation.…”

Section: Discussionmentioning

confidence: 99%

Gene expression alterations in the non-neoplastic parenchyma adjacent to infiltrating pancreatic ductal adenocarcinoma

et al. 2005

View full text Add to dashboard Cite

The non-neoplastic pancreatic parenchyma adjacent to infiltrating ductal adenocarcinoma demonstrates inflammation, fibrosis, acinar cell loss and small duct-like metaplasia of acinar cells. Similar morphologic changes are also observed in the setting of chronic pancreatitis. In addition, peritumoral acini have been shown to have alterations in gene expression even in the absence of morphological changes. To better understand the pancreatic acinar responses to infiltrating pancreatic ductal adenocarcinoma, we characterized gene expression patterns of pancreatic acinar tissue adjacent to infiltrating pancreatic ductal adenocarcinomas and compared them to gene expression patterns of acinar tissue affected by chronic pancreatitis as well as to those of normal pancreatic acini. Fresh-frozen pancreatic acinar tissue was microdissected from nine patients (three with pancreatic cancer, three with chronic pancreatitis, three with normal pancreata) using laser capture microdissection, and extracted RNA from each microdissection was subjected to two rounds of linear amplification and hybridized to oligonucleotide microarrays. Gene expression patterns were confirmed using quantitative RT-PCR and/or immunohistochemistry. A total of 20 genes was found to be overexpressed in peritumoral acinar tissue compared to normal acinar tissue and to acini affected by chronic pancreatitis. These 20 genes included pancreatitis-associated protein (HIP/PAP), a gene known to be overexpressed in acini adjacent to infiltrating pancreatic cancer, and the gene cartilage glycoprotein-39 (HC gp-39 or TKL-40). Serum HC gp-39 protein levels were significantly higher in patients with pancreatic cancer and in those with chronic pancreatitis than in controls without pancreatic disease. There was no significant difference in the levels of serum HC gp-39 in patients with pancreatic cancer and those with chronic pancreatitis. Our results demonstrate some of the molecular alterations in acinar cells that occur in response to adjacent infiltrating pancreatic ductal adenocarcinoma and reveal that such alterations can provide a rich source of markers of pancreatic cancer.

show abstract

Section: Discussionmentioning

confidence: 99%

Gene expression alterations in the non-neoplastic parenchyma adjacent to infiltrating pancreatic ductal adenocarcinoma

et al. 2005

View full text Add to dashboard Cite

show abstract

“…IgG4-RD including ISC was originally suspected to be an autoimmune disorder based on its frequent association with serological autoimmune abnormalities (e.g., ANA positivity) and steroid responsiveness [93,94]. However, this possibility has been questioned.…”

Section: Etiologymentioning

confidence: 99%

IgG4-related sclerosing cholangitis: all we need to know

2016

View full text Add to dashboard Cite

Our knowledge and experience of IgG4-related sclerosing cholangitis (ISC) have expanded in the last decade. ISC is one of the common organ manifestations of IgG4-related disease (IgG4-RD); approximately 60 % of patients with this systemic condition have ISC in the proximal and/or distal bile ducts. ISC needs to be discriminated from primary sclerosing cholangitis, cholangiocarcinoma, and other rare forms of lymphoplasmacytic cholangiopathy (e.g., follicular cholangitis and sclerosing cholangitis with granulocytic epithelial lesions). Its diagnosis requires a multidisciplinary approach, in which serology, histology, and imaging play crucial roles. Treatments with high-dose corticosteroids typically lead to the rapid and consistent induction of disease remission. Another promising therapeutic approach is B-cell depletion with rituximab. Although disease relapse is relatively common, provided that appropriate treatments are administered, ISC is considered a ''benign'' disease with a low risk of liver failure and biliary malignancy. Its molecular pathology is characterized by Th2-dominant immune reactions, regulatory T-cell activation, and CCL1-CCR8 interactions. Particular subsets of B cells such as plasmablasts and regulatory B cells also expand. A recent global proteomic study demonstrated that three significantly activated immunological cascades in ISC were all B-cell-or immunoglobulin-related (Fc-gamma receptormediated phagocytosis, B-cell receptor signaling pathway, and Fc-epsilon receptor I signaling pathway), suggesting the crucial roles of B cells in the underlying immune reactions. Despite the expansion of our knowledge of the pathophysiology of ISC, the exact role of IgG4 remains unclear. A better understanding of its immunopathology will offer some potential drug targets for this emerging biliary disease.

show abstract

“…The positive rates in AIP are 50-60, 60-80 and 68-92% for c-globulin, IgG and IgG4, respectively [30,50,51]. Serum IgG4 is superior to IgG with a sensitivity of 86%, a specificity of 96% and accuracy of 91% in differentiation of AIP from pancreatic cancer, compared to 69, 75 and 72% for IgG [52].…”

Section: Immunoglobulinsmentioning

confidence: 99%

“…Representative examples include anti-lactoferrin antibody (ALF), anti-carbonic anhydrase II antibody (CA-II), ANA and Rheumatoid factor (RF) with the respective frequency of 75, 55, 60 and 20-30% [51]. The Japanese Clinical Criteria 2006 employed ANA and RF as serum markers of AIP (Table 1).…”

Section: Antibodiesmentioning

confidence: 99%

Autoimmune pancreatitis in Japan: overview and perspective

Shimosegawa

Kanno

2009

J Gastroenterol

View full text Add to dashboard Cite

Since the rediscovery and definition of autoimmune pancreatitis (AIP) by Yoshida et al. in 1995, the disease has been attracting attention because of its unique clinical features and practical issues. This disease shows very impressive imaging findings, serological changes, and characteristic histopathology. It occurs most commonly in elderly males with painless jaundice or mild abdominal pain; resemblance in imaging findings between AIP and pancreatobiliary cancers poses an important practical issue of differentiation. With increasing recognition of AIP and accumulation of cases, another important feature of this disease has been revealed, i.e

show abstract

Autoimmune-related pancreatitis is associated with autoantibodies and a Th1/Th2-type cellular immune response

Cited by 506 publications

References 39 publications

Gene expression alterations in the non-neoplastic parenchyma adjacent to infiltrating pancreatic ductal adenocarcinoma

Gene expression alterations in the non-neoplastic parenchyma adjacent to infiltrating pancreatic ductal adenocarcinoma

IgG4-related sclerosing cholangitis: all we need to know

Autoimmune pancreatitis in Japan: overview and perspective

Contact Info

Product

Resources

About