Premium
Analysis of VH gene rearrangement and somatic hypermutation in type 1 autoimmune pancreatitis
Author(s) -
Okumura Fumihiro,
Sakuma Hidenori,
Nakazawa Takahiro,
Hayashi Kazuki,
Naitoh Itaru,
Miyabe Katsuyuki,
Yoshida Michihiro,
Yamashita Hiroaki,
Ohara Hirotaka,
Inagaki Hiroshi,
Joh Takashi
Publication year - 2012
Publication title -
pathology international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.73
H-Index - 74
eISSN - 1440-1827
pISSN - 1320-5463
DOI - 10.1111/j.1440-1827.2012.02788.x
Subject(s) - somatic hypermutation , autoimmune pancreatitis , biology , antibody , gene rearrangement , immunoglobulin heavy chain , pathogenesis , pancreatitis , gene , immunoglobulin gene , microbiology and biotechnology , immunology , genetics , pancreas , medicine , b cell , endocrinology
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.