Analysis of VH gene rearrangement and somatic hypermutation in type 1 autoimmune pancreatitis
Analysis of VH gene rearrangement and somatic hypermutation in type 1 autoimmune pancreatitis
复制标题
1型自身免疫性胰腺炎VH基因重排及体细胞超突变分析
DOI：
10.1111/j.1440-1827.2012.02788.x
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发表时间：
2012
影响因子：
2.2
通讯作者：
Joh T.
中科院分区：
文献类型：
--
作者：
Okumura F;Sakuma H;Nakazawa T;Hayashi K;Naitoh I;Miyabe K;Yoshida M;Yamashita H;Ohara H;Inagaki H;Joh T.
1型自身免疫性胰腺炎（AIP）是称为免疫球蛋白G4相关性全身性疾病的全身性纤维炎性疾病的胰腺表现。虽然这种炎症过程被认为是一种具有自身免疫机制的疾病，但其发病机制仍不清楚。为了阐明B细胞浸润病变的特点，我们分析了免疫球蛋白重链可变区（VH）基因重排和体细胞超突变的侵袭性淋巴细胞在1型AIP（n= 3），与梗阻性胰腺炎（n= 3）作为对照。从受影响的炎性病变中提取DNA。PCR扩增重组VH基因后，将克隆进行亚克隆，随机选择重组克隆进行测序。每个病例分析超过60个克隆。所有病例均未检出单克隆VH重排。无1型AIP和梗阻性胰腺炎特异性VH家族或VH片段。但1型AIP中未突变VH片段的检出率（17%）高于梗阻性胰腺炎（5.1%）（P= 0.010）。我们的研究表明，未突变或较少突变的VH基因的增加率可能是1型AIP的特征，并可能在这种疾病的发展中发挥作用。
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 rearrangedVHgene, the clones were subcloned, and recombinant clones were randomly selected and sequenced. More than 60 clones per case were analyzed. MonoclonalVHrearrangement was not detected in any of the cases examined. There was noVHfamily orVHfragment specific to type 1 AIP and obstructive pancreatitis. However, the rate of unmutatedVHfragments 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.