IL-8 Expression in Granulocytic Epithelial Lesions of Idiopathic Duct-centric Pancreatitis (Type 2 Autoimmune Pancreatitis)

Abstract

Type 2 autoimmune pancreatitis (type 2 AIP) develops in isolation or sometimes in association with ulcerative colitis. Its diagnosis requires the histologic confirmation of granulocytic epithelial lesions (GELs) with no diagnostic biomarker currently available. This study aimed to elucidate the tissue expression of cytokines and their diagnostic value in this condition. In quantitative polymerase chain reaction for multiple cytokines using tissue-derived mRNA, the expression level of interleukin (IL)-8 was markedly higher in type 2 AIP than in type 1 AIP (P<0.001). In immunostaining, IL-8 expression was detected in the ductal/ductular epithelium (11/13; 85%) and infiltrating neutrophils or lymphocytes (12/12; 100%) in type 2 AIP, but was almost entirely negative in type 1 AIP (n=13; both, P<0.001). Although obstructive pancreatitis adjacent to pancreatic cancers (peritumoral pancreatitis) exhibited IL-8 expression in the epithelium (3/12; 25%) and inflammatory cells (10/12; 83%), expression levels were significantly lower than those in type 2 AIP (P<0.001 and 0.020, respectively). The presence of either GELs or IL-8-positive epithelium discriminated type 2 AIP from type 1 AIP or obstructive pancreatitis with 92% sensitivity and 92% to 100% specificity. Furthermore, CD3/IL-8-coexpressing lymphocytes were almost restricted to type 2 AIP. Interestingly, a similar pattern of IL-8 expression was also observed in colonic biopsies of ulcerative colitis. In conclusion, the overexpression of IL-8 may underlie the development of GELs in type 2 AIP, and IL-8 immunostaining or IL-8/CD3 double staining may become an ancillary method for its diagnosis. The similar expression pattern of IL-8 in ulcerative colitis also suggests a pathogenetic link between the 2 conditions.

Tumefactive Inflammatory Diseases of the Pancreas

“…The American Journal of Pathologyajp.amjpathol.org A recent study of cytokine expression in pancreatic tissue samples from patients with type 2 autoimmune pancreatitis 59 revealed almost undetectable levels of IL4, IL10, and TNFA mRNA, highlighting the immunologic differences between the two forms of autoimmune pancreatitis. 59 The expression of INFG mRNA was comparable between types 1 and 2 autoimmune pancreatitis, whereas higher expression of CXCL8 (alias IL-8) mRNA was observed in type 2 disease, 13-fold higher than type 1 disease. 59 On immunostaining, the major source of CXCL8 appeared to be neutrophils, T cells, and damaged duct/ductular epithelium (Figure 2).…”

Duct‐obstructive pancreatitis with granulocytic epithelial lesion in a patient with ulcerative colitis: An atypical manifestation of type 2 autoimmune pancreatitis?

“…6 We recently reported that IL-8 (CXCL8) was overexpressed in type 2 AIP. 8 This chemotactic factor for neutrophils was expressed in the duct/ductular epithelium (83% of patients) and infiltrating inflammatory cells (100%) of patients with type 2 AIP. The aberrant expression of IL-8 in the epithelium was only focally observed in type 1 AIP or peritumoral pancreatitis.…”

“…Double immunostaining also revealed that CD3‐positive T‐lymphocytes infiltrating in type 2 AIP expressed IL‐8, whereas CD3/IL‐8 double positive cells were not present in type 1 AIP or peritumoral pancreatitis. Although the diagnostic sensitivity of pancreatic biopsies for type 2 AIP was 50% based on the presence of GELs, it increased to more than 90% with IL‐8 immunostaining …”

“…We recently reported that IL‐8 (CXCL8) was overexpressed in type 2 AIP . This chemotactic factor for neutrophils was expressed in the duct/ductular epithelium (83% of patients) and infiltrating inflammatory cells (100%) of patients with type 2 AIP.…”

“…Although the diagnostic sensitivity of pancreatic biopsies for type 2 AIP was 50% based on the presence of GELs, it increased to more than 90% with IL-8 immunostaining. 8 Rare examples of type 1 AIP present with duct obstruction causing upstream ductal dilatation and/or pseudocysts, 9,10 whereas this relationship has not been confirmed for type 2 AIP. We herein present a patient with ulcerative colitis who underwent distal pancreatectomy for a suspected intraductal papillary mucinous neoplasm, which showed some microscopic features similarities to type 2 AIP.…”