Challenge in the Pathogenesis of Autoimmune Pancreatitis: Potential Role of Helicobacter pylori Infection via Molecular Mimicry

Kountouras, Jannis; Zavos, Christos; Gavalas, Emmanuel; Tzilves, Dimitrios

doi:10.1053/j.gastro.2007.05.044

Cited by 51 publications

(34 citation statements)

References 5 publications

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“…The PBP peptide newly identified in European patients with AIP shows homology with an amino acid sequence of PBP of H. pylori and with the ubiquitin-protein ligase E3 component n-recognin 2 (UBR2), an enzyme highly expressed in acinar cells of the pancreas, while European patients with AIP did not necessarily show LPSP as the typical histopathology of type 1 AIP in IgG4-related diseases [65]. These findings suggest that gastric H. pylori infection might trigger AIP in genetically predisposed subjects [68][69][70].…”

Section: The Complement Systemmentioning

confidence: 90%

“…Molecular mimicry among microbes and target antigens may be a possible mechanism for breaking down immune tolerance. This hypothesis is based on the concept that infectious agents share one or more epitopes with selfcomponents, or infectious agents cause bystander activation of immune cells with autoaggressive potential [68][69][70]. Guarneri and colleagues showed significant homology between human CA-II and alpha-CA of Helicobacter pylori, a fundamental enzyme for bacterial survival and proliferation in the stomach [70].…”

Section: The Complement Systemmentioning

confidence: 99%

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Recent advances in the concept and diagnosis of autoimmune pancreatitis and IgG4-related disease

et al. 2011

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Recent studies have suggested the existence of two subtypes of autoimmune pancreatitis (AIP): type 1 AIP, related to IgG4 (lymphoplasmacytic sclerosing pancreatitis); and type 2 AIP, related to a granulocytic epithelial lesion (idiopathic duct-centric chronic pancreatitis). Compared with type 2 AIP, the clinicopathological features of type 1 AIP, with increased serum IgG4/IgE levels, abundant infiltration of IgG4 + plasmacytes and lymphocytes, autoantibodies, and steroid responsiveness, are more suggestive of abnormal immunity such as allergy or autoimmunity. Moreover, patients with type 1 AIP often have extrapancreatic lesions, such as sclerosing cholangitis, sclerosing sialadenitis, or retroperitoneal fibrosis, showing pathological features similar to those of the pancreatic lesions. Based on these findings, an international concept of and diagnostic criteria for AIP have been proposed recently. Of interest, many synonyms have been proposed for the conditions of AIP and extrapancreatic lesions associated with IgG4, such as "multifocal idiopathic fibrosclerosis," "IgG4-related autoimmune disease," "IgG4-related sclerosing disease," "systemic IgG4-related plasmacytic syndrome (SIPS)," and "IgG4-related multiorgan lymphoproliferative syndrome," all of which may refer to the same conditions. Therefore, the Japanese Research Committee for "Systemic IgG4-Related Sclerosing Disease" proposed a disease concept and clinical diagnostic criteria based on the concept of multifocal fibrosclerosing disease, in 2009, in which the term "IgG4-related disease" was agreed upon as a minimal consensus to cover these conditions. Although the significance of IgG4 in the development of "IgG4-related disease" remains unclear, we have proposed a hypothesis for the development of type 1 AIP, one of the IgG4-related diseases. The concept and diagnostic criteria of "IgG4-related disease" will be changed in accordance with future studies.

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Section: The Complement Systemmentioning

confidence: 90%

Section: The Complement Systemmentioning

confidence: 99%

Recent advances in the concept and diagnosis of autoimmune pancreatitis and IgG4-related disease

et al. 2011

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“…This hypothesis is based on the concept that infectious agents share one or more epitopes with self-components, or infectious agents cause bystander activation of immune cells with autoaggressive potential. [59][60][61] Guarneri and colleagues 61 showed signifi cant homology between human CA-II and alpha-CA of Helicobacter pylori, a fundamental enzyme for bacterial survival and proliferation in the stomach. 61 Moreover, the homologous segments contain the binding motif of DRB1*0405, which confers risk for AIP development.…”

Section: Humoral Immunity and Target Antigensmentioning

confidence: 99%

Recent advances in autoimmune pancreatitis: concept, diagnosis, and pathogenesis

2008

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Recent advances support the concept of autoimmune pancreatitis (AIP) as a unique systemic disease, because it shows occasional extrapancreatic lesions such as sclerosing cholangitis, sclerosing sialoadenitis, and retroperitoneal fibrosis, pathological features similar to those of fibrosis, and abundant infiltration of IgG4-positive plasma cells, and it is steroid responsive. Based on these findings, several diagnostic criteria have been proposed. Although AIP is accepted worldwide as a unique clinical entity, its pathogenetic mechanism remains unclear. To clarify its pathogenesis, its genetic background, humoral immunity, candidate target antigens including self-antigens and molecular mimicry by microbes, and cellular immunity including regulatory T cells, the complement system, and experimental models are reviewed. On the basis of this review, we hypothesize that the pathogenesis of AIP involves a biphasic mechanism consisting of "induction" and "progression." In the early stage, the initial response to self-antigens [lactoferrin, carbonic anhydrase (CA)-II, CA-IV, pancreatic secretory trypsin inhibitor, and alpha-fodrin] and molecular mimicry (Helicobacter pylori) are induced by decreased naïve regulatory T cells (Tregs), and T-helper (Th) 1 cells release proinflammatory cytokines [interferon-gamma, interleukin (IL)-1beta, IL-2, and tumor necrosis factor alpha]. In the chronic stage, progression is supported by increased memory Tregs and Th2 immune responses. The classical complement system pathway may be activated by the IgG1 immune complex. As Tregs seem to play an important role in progression as well as in induction of the disease, further studies are necessary to clarify the pathogenesis of AIP.

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“…Molecular mimicry among microbes and target antigens may be a possible mechanism to break down immune tolerance. The hypothesis is based on the concept that infectious agents share one or more epitopes with selfcomponents, or infectious agents cause bystander activation of immune cells with autoaggressive potential [62][63][64]. Guarneri and colleagues showed a significant homology between human CA-II and alpha-CA of Helicobacter pylori, a fundamental enzyme for bacterial survival and proliferation in the stomach [64].…”

Section: Autoantibodiesmentioning

confidence: 99%

Autoimmune pancreatitis—a new evolving pancreatic disease?

Okazaki

Uchida

Fukui

et al. 2010

Langenbecks Arch Surg

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Challenge in the Pathogenesis of Autoimmune Pancreatitis: Potential Role of Helicobacter pylori Infection via Molecular Mimicry

Cited by 51 publications

References 5 publications

Recent advances in the concept and diagnosis of autoimmune pancreatitis and IgG4-related disease

Recent advances in the concept and diagnosis of autoimmune pancreatitis and IgG4-related disease

Recent advances in autoimmune pancreatitis: concept, diagnosis, and pathogenesis

Autoimmune pancreatitis—a new evolving pancreatic disease?

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