title: Analysis of VH gene rearrangement and somatic hypermutation in type 1 autoimmune pancreatitis.
abstract: Type 1 autoimmune pancreatitis (AIP) is the pancreatic manifestation of systemic fibroinflammatory disease called immunoglobulin G4-associated systemic disease. Although this inflammatory process is considered to be a disease with an autoimmune mechanism, its pathogenesis still remains unclear. To clarify the characteristics of B cells infiltrating the lesion, we analyzed the immunoglobulin heavy chain variable region (VH) gene rearrangement and somatic hypermutation of invasive lymphoid cells in type 1 AIP (n= 3), in comparison with obstructive pancreatitis (n= 3) as a control. DNA was extracted from the affected inflammatory lesions. After PCR amplification of the rearranged VH gene, the clones were subcloned, and recombinant clones were randomly selected and sequenced. More than 60 clones per case were analyzed. Monoclonal VH rearrangement was not detected in any of the cases examined. There was no VH family or VH fragment specific to type 1 AIP and obstructive pancreatitis. However, the rate of unmutated VH fragments in type 1 AIP (17%) was higher than that in obstructive pancreatitis (5.1%) (P= 0.010). Our study suggests that an increased rate of unmutated or less mutated VH genes may be characteristic of type 1 AIP and might play a role in the development of this disease.
authors.affiliation: Departments of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
authors.forename: Fumihiro
authors.initials: F
authors.lastname: Okumura
authors.forename: Hidenori
authors.initials: H
authors.lastname: Sakuma
authors.forename: Takahiro
authors.initials: T
authors.lastname: Nakazawa
authors.forename: Kazuki
authors.initials: K
authors.lastname: Hayashi
authors.forename: Itaru
authors.initials: I
authors.lastname: Naitoh
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Miyabe
authors.forename: Michihiro
authors.initials: M
authors.lastname: Yoshida
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Yamashita
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Ohara
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Inagaki
authors.forename: Takashi
authors.initials: T
authors.lastname: Joh
mesh_terms: D000328:Adult; D000368:Aged; D001327:Autoimmune Diseases / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D005260:Female; D015321:Gene Rearrangement; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics* / Q000276:immunology; D007135:Immunoglobulin Variable Region / Q000235:genetics* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D010195:Pancreatitis / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D027041:Somatic Hypermutation, Immunoglobulin / Q000235:genetics* / Q000276:immunology
chemical_list: D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region