Analysis of IgG4 class switch-related molecules in IgG4-related disease.

Analysis of IgG4 class switch-related molecules in IgG4-related disease.
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DOI:
10.1186/ar3924
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发表时间:
2012-07-23
影响因子:
4.9
通讯作者:
Sumida T
Sumida T
中科院分区:
医学2区
文献类型:
--
作者:
Tsuboi H;Matsuo N;Iizuka M;Tsuzuki S;Kondo Y;Tanaka A;Moriyama M;Matsumoto I;Nakamura S;Sumida T

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免疫球蛋白G4(IgG 4)相关疾病(IgG 4-RD)是一种新的疾病实体,其特征是高血清IgG 4水平,IgG 4阳性浆细胞浸润和各种器官的纤维化。本研究的目的是确定IgG 4-RD中IgG 4类别转换重组的上调机制。我们从IgG 4-RD(n = 6)、干燥综合征(SS)(n = 6)和健康对照(n = 8)患者的外周血单核细胞(PBMC)中提取RNA,从从IgG 4-RD(n = 3)、SS(n = 4)和健康对照(n = 4)患者的PBMC中分选的CD 3阳性T细胞和CD 20阳性B细胞中提取RNA,以及来自IgG 4-RD(n = 11)、SS(n = 13)患者和健康对照(n = 3)的唇唾液腺(LSG)。用定量PCR检测IgG 4特异性类转换相关分子如Th 2细胞因子(IL-4和IL-13)、Treg细胞因子(IL-10和TGF-β)和转录因子(GATA 3和Foxp 3)的mRNA表达水平。还检查了IgG 4非特异性类别转换相关分子,如CD 40、CD 154、BAFF、APRIL、IRF 4和AID。IgG 4-RD的LSG中Treg细胞因子(IL-10和TGF-β)和AID的表达水平显著高于SS和对照组(均P < 0.05)。IgG 4-RD组PBMC中CD 40和CD 154的表达均显著低于SS组(P < 0.05),而CD 20阳性B细胞中的CD 40和CD 3阳性T细胞中的CD 154在三组间无显著差异。LSGs中IL-10、TGF-β和AID的过度表达可能在IgG 4-RD的发病机制中发挥重要作用,如IgG 4特异性类别转换重组和纤维化。IgG 4类别转换重组似乎主要在受影响的器官中上调。
Immunoglobulin G4 (IgG4)-related disease (IgG4-RD) is a new disease entity characterized by high serum IgG4 levels, IgG4-positive plasmacytic infiltration, and fibrosis in various organs. The purpose of this study was to determine the mechanism of upregulation of IgG4 class switch recombination in IgG4-RD. We extracted RNA from peripheral blood mononuclear cells (PBMCs) of patients with IgG4-RD (n = 6), Sjögren syndrome (SS) (n = 6), and healthy controls (n = 8), from CD3-positive T cells and CD20-positive B cells sorted from PBMCs of patients with IgG4-RD (n = 3), SS (n = 4), and healthy controls (n = 4), as well as from labial salivary glands (LSGs) of patients with IgG4-RD (n = 11), SS (n = 13), and healthy controls (n = 3). The mRNA expression levels of IgG4-specific class switch-related molecules, such as Th2 cytokines (IL-4 and IL-13), Treg cytokines (IL-10 and TGF-β), and transcriptional factors (GATA3 and Foxp3) were examined with quantitative polymerase chain reaction (PCR). IgG4-nonspecific class switch-related molecules, such as CD40, CD154, BAFF, APRIL, IRF4, and AID, were also examined. The expression levels of Treg cytokines (IL-10 and TGF-β) and AID were significantly higher in LSGs of IgG4-RD than in SS and the controls (P < 0.05, each). In contrast, those of CD40 and CD154 were significantly lower in PBMCs of IgG4-RD than in SS (P < 0.05, each), whereas CD40 in CD20-positive B cells and CD154 in CD3-positive T cells were comparable in the three groups. Overexpression of IL-10, TGF-β, and AID in LSGs might play important roles in the pathogenesis of IgG4-RD, such as IgG4-specific class-switch recombination and fibrosis. IgG4 class-switch recombination seems to be mainly upregulated in affected organs.
DOI: 10.1158/1078-0432.ccr-08-1845
发表时间: 2009-05-01
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作者:
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发表时间: 2011-10
期刊: Growth factors (Chur, Switzerland)
影响因子: --
作者:
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DOI: 10.1097/mpa.0b013e3181577553
发表时间: 2008-03-01
期刊: PANCREAS
影响因子: 2.9
作者:
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通讯作者: Okazaki, Kazuichi
DOI: 10.1007/s10165-007-0010-3
发表时间: 2008-02-01
影响因子: 2.2
作者:
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通讯作者: Nakamura, Seiji