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

Abstract

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.

IgG4-Associated Tubulointerstitial Nephritis: Two Case Reports and a Literature Review

“…The roles of IgG4 and its corresponding antigens in the pathogenesis of IgG4-related diseases remain unknown. Autoimmune or allergic mechanisms have been discussed (35)(36)(37). The increased peripheral blood count of eosinophils in Case 1 and the renal infiltration of eosinophils in Case 2 suggest that allergic reactions might play a role in the pathogenesis of IgG4-RSD, even in patients without histories of allergies or exposure to allergens.…”

Autoimmune Pancreatitis-What is Known, What Needs to be Known

“…It has also been observed that increased peripheral inducible memory T-reg cells correlate with serum levels of IgG 4 , suggesting that the elevated IgG 4 level does not act as a pathogenic factor in this disease but rather as an anti-inflammatory factor. This would explain why serum IgG 4 level is not universally increased in these patients and the observation that lower IgG 4 levels are sometimes discovered further in disease course and in more severe presentations [7].…”

A review of liver disorders in inflammatory bowel disease (IBD)

“…IAC has been described in patients with UC and is a IgG4-related systemic disease causing biliary destruction similar to PSC [96]. Although 9% to 36% of patients with PSC may have elevated IgG4; these levels are lower than in patients with IAC [97,98] and hence the tissue diagnosis of IgG4 plasma cell infiltration in the bile duct has greater diagnostic utility [96,99].…”