Recent concept of autoimmune-related pancreatitis

Okazaki, Kazuichi; Uchida, Kazushige; Chiba, Tsutomu

doi:10.1007/s005350170094

Cited by 141 publications

(181 citation statements)

References 50 publications

(117 reference statements)

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“…In the present study, we also detected an autoantibody against pancreas-specific AMY-2A in all of the AIP patients, but not in patients with chronic alcoholic pancreatitis and with pancreatic tumors. The presence of autoantibodies against CAII, lactoferrin, and pancreatic secretory trypsin inhibitor (PSTI) has been reported (3,4,19). However, the distribution of these molecules is non-organ specific (20 -22), and the prevalence of these autoantibodies against CAII, lactoferrin, and PSTI in AIP is rather low, ranging from 42ϳ73% (3,4,19).…”

Section: Discussionmentioning

confidence: 99%

“…It is characterized by 1) irregular narrowing of the main pancreatic duct and swelling of the pancreas, both of which are due to abundant lymphoplasmacytic inflammation to the exocrine pancreas (2); 2) the increased serum level of IgG and IgG4; 3) positive autoantibodies such as lactoferrin autoantibody or carbonic anhydrase II (CAII) autoantibody (3,4); and 4) a high prevalence of diabetes with complications (5).…”

mentioning

confidence: 99%

“…It is difficult to distinguish AIP from other types of chronic pancreatitis or cancer of the pancreatic head (8). In such cases, detection of autoantibodies is useful for diagnosing AIP, but a proportion of patients with AIP are negative for autoantibodies against lactoferrin and CAII (3,4).…”

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confidence: 99%

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Amylase α-2A Autoantibodies

et al. 2009

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OBJECTIVE-The pathogenesis of autoimmune pancreatitis (AIP) and fulminant type 1 diabetes remains unclear, although it is known that immune-mediated processes severely compromise the endocrine and exocrine functions in both diseases. RESEARCH DESIGN AND METHODS-We have screened aTriplEx2 human pancreas cDNA library with serum from a patient with AIP and obtained positive clones. Sequence analysis revealed that 7 of 10 clones were identical to human amylase ␣-2A. Using a recombinant COOH-terminal amylase ␣-2A protein, we developed an enzyme-linked immunosorbent assay system to detect autoantibodies against human amylase ␣-2A.RESULTS-All 15 serum samples from patients with AIP recognized the recombinant protein, whereas sera from 25 patients with chronic alcoholic pancreatitis and sera from 25 patients with a pancreas tumor did not. Interestingly, 88% (15/17) of patients with fulminant type 1 diabetes were positive for an autoantibody against amylase ␣-2A. These antibodies were detected in 21% of patients with acute-onset type 1 diabetes (9 of 42) and 6% of type 2 diabetic patients (4 of 67).CONCLUSIONS-These results suggest that an autoantibody against amylase ␣-2A is a novel diagnostic marker for both AIP and fulminant type 1 diabetes and that, clinically and immunologically, AIP and fulminant type 1 diabetes are closely related. Diabetes 58:732-737, 2009 R ecently, autoimmune pancreatitis (AIP), a unique form of chronic pancreatitis, has been reported as a discrete disease entity (1). It is characterized by 1) irregular narrowing of the main pancreatic duct and swelling of the pancreas, both of which are due to abundant lymphoplasmacytic inflammation to the exocrine pancreas (2); 2) the increased serum level of IgG and IgG4; 3) positive autoantibodies such as lactoferrin autoantibody or carbonic anhydrase II (CAII) autoantibody (3,4); and 4) a high prevalence of diabetes with complications (5).We recently reported that a high proportion of pancreatic islets and exocrine pancreatic tissues were infiltrated by CD4 ϩ or CD8 ϩ T-cells in the inflammatory process, which might induce diabetes in AIP (6). In addition, treatment with prednisolone improved insulin secretion and glycemic control in AIP patients (5). These data support the concept that autoimmune mechanism(s) plays a pivotal role in the destruction of the endocrine and exocrine pancreas in AIP patients with diabetes.Clinically, the most common initial symptom of AIP is jaundice, but in some patients, no symptoms or only mild symptoms, frequently without acute attacks of pancreatitis, may be present (7). It is difficult to distinguish AIP from other types of chronic pancreatitis or cancer of the pancreatic head (8). In such cases, detection of autoantibodies is useful for diagnosing AIP, but a proportion of patients with AIP are negative for autoantibodies against lactoferrin and CAII (3,4).We encountered an AIP patient whose serum IgG and IgG4 levels were 3,498 and 2,430 mg/dl, respectively. It has been reported that median levels (5th and 95th percentile...

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Section: Discussionmentioning

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Amylase α-2A Autoantibodies

et al. 2009

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“…5) [39,40]. Up to 80% of AIP patients show biliary stenosis, most frequently seen in the lower part of the common bile duct, but also capable of occurring in any part of extra or intrahepatic biliary tract [36,[41][42][43].…”

Section: Endoscopic Retrograde Cholangiopancreaticographymentioning

confidence: 99%

Autoimmune pancreatitis in Japan: overview and perspective

Shimosegawa

Kanno

2009

J Gastroenterol

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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

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“…IgG4 comprises approximately 4% of the total circulating serum IgG in normal adults, but has been reported to be elevated in autoimmune pancreatitis in 62-94% of patients. [23][24][25][26][27][28] Increasingly, studies have also found elevated numbers of IgG4-positive plasma cells by tissue immunohistochemistry in autoimmune pancreatitis. Most recently, Deheragoda et al 11 demonstrated an 85% sensitivity in autoimmune pancreatitis patients for 410 IgG4-positive plasma cells per high power field in both pancreatic and extrapancreatic tissues in comparison to 0.6% of specimens from controls of normal pancreata (n ¼ 10) and pancreatic ductal adenocarcinomas (n ¼ 20).…”

Section: Discussionmentioning

confidence: 99%

The role of Movat pentachrome stain and immunoglobulin G4 immunostaining in the diagnosis of autoimmune pancreatitis

et al. 2009

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Autoimmune pancreatitis is highly responsive to steroid therapy, but because it mimics pancreatic cancer, it often precipitates unnecessary surgery. Adequate diagnostic tests are needed to permit appropriate medical therapy. Lymphocytic and obliterative phlebitis are reported in the majority of cases, as are elevated IgG4-positive plasma cells, indicating their high sensitivity. Their specificities, especially when used in conjunction, however, remain largely unknown. Movat pentachrome vascular and IgG4 immunohistochemical stains were performed on a total of 15 autoimmune pancreatitis cases (11 pancreatic resections and 4 biopsies), 39 usualtype alcoholic or idiopathic chronic pancreatitis cases, 35 pancreatic ductal adenocarcinoma-associated chronic pancreatitis cases, and 29 normal pancreata. Marked and diffuse lymphocytic and obliterative venulitis were detected in all 15 cases of autoimmune pancreatitis on Movat staining (100% sensitivity). Only a single carcinoma-associated chronic pancreatitis case among all of the controls showed diffuse benign venulitis that was nonobliterative (99% specificity). Nine of 13, 9 autoimmune pancreatitis cases showed marked IgG4 immunopositivity at X10 positive plasma cells per Â 400 field (69% sensitivity). No increased IgG4 plasma cells were found in any of 103 controls (100% specificity). In combination, all of the autoimmune pancreatitis cases had at least one (13/13) and most had both markers (9/13), whereas none of the controls had both markers. Overall, these combined stains show very promising diagnostic utility and should be considered in combination with clinical and serologic analyses in the evaluation of chronic pancreatitis suspicious for malignancy. Future validating studies on preoperative biopsies with outcome data following steroid therapy will be essential.

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Recent concept of autoimmune-related pancreatitis

Cited by 141 publications

References 50 publications

Amylase α-2A Autoantibodies

Amylase α-2A Autoantibodies

Autoimmune pancreatitis in Japan: overview and perspective

The role of Movat pentachrome stain and immunoglobulin G4 immunostaining in the diagnosis of autoimmune pancreatitis

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