review of literature on clinical pancreatology - The Pancreapedia

manifestation <strong>of</strong> a systemic IgG4-related autoimmune disease. These patients are typicallyolder than 50 years and male. Large series reported from Europe and the United Statesconsistently identify a second set <strong>of</strong> patients with slightly different histopathologic changesthat have been called idiopathic duct-centric chronic pancreatitis (IDCP) or AIP withgranulocytic epithelial lesions (GELs). This subgroup <strong>of</strong> patients is more diverse in age,includes a higher fraction <strong>of</strong> female patients, and characteristically does not have elevatedplasma IgG4. These patients may have chronic inflammatory bowel disease such asulcerative colitis, but typically lack evidence <strong>of</strong> extrapancreatic involvement <strong>of</strong> the organstypical <strong>of</strong> IgG4-related autoimmune disease. More recently, these two patterns have beendesignated as AIP types 1 and 2. In the United States and Europe, type 1 AIP (LPSP) ismore common than type 2 (IDCP/AIP with GELs) in series that identify both types. Bothtypes <strong>of</strong> AIP share a number <strong>of</strong> histopathologic features most notably a periductallymphoplasmacytic infiltrate and a phlebitis. Only the concomitant duct infiltration byneutrophilic granulocytes, the GEL, and a less marked phlebitis distinguish the histologicalchanges <strong>of</strong> type 2 from type 1 AIP. A fraction <strong>of</strong> patients with type 2 AIP also hasinflammatory bowel disease, and one had multiple sclerosis (some forms <strong>of</strong> multiple sclerosisare considered to be <strong>of</strong> autoimmune origin). Type 2 AIP patients may also show biliaryinvolvement similar to that seen in type 1 AIP. Finally, both types 1 and 2 AIP cases reveal asimilar increase in the numbers <strong>of</strong> CD4 and CD lymphocytes that infiltrate the pancreas. Inaggregate, these observations provide a significant support for an autoimmune mechanismin the pathogenesis <strong>of</strong> type 2 AIP. The issue <strong>of</strong> core biopsies to diagnose AIP has been apoint <strong>of</strong> contention. Whereas the Mayo group has published on the technical aspects andusefulness <strong>of</strong> endoscopic ultrasoundguided pancreatic core biopsies and routinely uses it toestablish the diagnosis <strong>of</strong> AIP, others have not found it as helpful in its ability to get sufficienttissue to make the diagnosis <strong>of</strong> either AIP or nonfocal chronic pancreatitis. The Americancriteria also differ sigificantly from the Japanese and Asian criteria in the use <strong>of</strong> serologicalmarkers. Whereas the American criteria use only serum IgG4, the Japanese and Asiancriteria use any one <strong>of</strong> immunoglobulin G, immunoglobulin G4, and autoantibodies such asantinuclear antibody and rheumatoid factor. However, unlike the American criteria, in theJapanese or Asian criteria, other organ involvement cannot be used as collateral evidence todiagnose AIP.It is believe that the presence <strong>of</strong> other organ involvement can be as helpful as,if not more helpful than, serological abnormalities in the diagnosis <strong>of</strong> AIP and should beincluded in the diagnostic armamentarium as suggested by the JCGAIP. In conclusion, thenew Japanese guidelines reflect progress in standardizing the diagnosis and treatment AIP.The recommendations also reveal differences in the experience <strong>of</strong> Japanese and Westernclinicians and pathologists that may require additional consideration for their applicationinternationally, or slight revision to create guidelines that are applicable worldwide [304].A new antibodyAutoimmune pancreatitis is characterized by an inflammatory process that leads to organdysfunction. The cause <strong>of</strong> the disease is unknown. Its autoimmune origin has beensuggested but never proved, and little is known about the pathogenesis <strong>of</strong> this condition. Toidentify pathogenetically relevant autoantigen targets, it was screened a random peptidelibrary with pooled IgG obtained from 20 patients with autoimmune pancreatitis. Peptidespecificantibodies were detected in serum specimens obtained from the patients. Among thedetected peptides, peptide AIP(1-7) was recognized by the serum specimens from 18 <strong>of</strong> 20patients with autoimmune pancreatitis and by serum specimens from 4 <strong>of</strong> 40 patients withpancreatic cancer, but not by serum specimens from healthy controls. The peptide showedhomology with an amino acid sequence <strong>of</strong> plasminogen-binding protein (PBP) <strong>of</strong>Helicobacter pylori and with ubiquitin-protein ligase E3 component n-recognin 2 (UBR2), anenzyme highly expressed in acinar cells <strong>of</strong> the pancreas. Antibodies against the PBP peptidewere detected in 19 <strong>of</strong> 20 patients with autoimmune pancreatitis (95 %) and in 4 <strong>of</strong> 40patients with pancreatic cancer (10 %). Such reactivity was not detected in patients withalcohol-induced chronic pancreatitis or intraductal papillary mucinous neoplasm. The results