Increase in B-cell-activation factor (BAFF) and IFN-γ productions by tonsillar mononuclear cells stimulated with deoxycytidyl-deoxyguanosine oligodeoxynucleotides (CpG-ODN) in patients with IgA nephropathy
Increase in B-cell-activation factor (BAFF) and IFN-γ productions by tonsillar mononuclear cells stimulated with deoxycytidyl-deoxyguanosine oligodeoxynucleotides (CpG-ODN) in patients with IgA nephropathy
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DOI：
10.1016/j.clim.2007.11.003
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发表时间：
2008-03-01
影响因子：
8.6
通讯作者：
Harabuchi, Yasuaki
中科院分区：
文献类型：
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作者：
Goto, Takashi;Bandoh, Nobuyuki;Harabuchi, Yasuaki
伊加肾病（IgAN）是原发性肾小球肾炎的最常见形式，被认为是扁桃体相关疾病，因为它通常在急性扁桃体炎之后和/或期间恶化，并且疾病进展通常通过扁桃体切除术来防止。虽然一些报告显示扁桃体单核细胞（TMCs）的伊加产生增加，但其机制尚未完全阐明。最近，B细胞活化因子（BAFF），刺激B细胞增殖和免疫球蛋白的生产，被确定。非甲基化脱氧胞苷脱氧鸟苷寡脱氧核苷酸（CpG-ODN）能够模拟微生物DNA的免疫刺激活性，参与免疫球蛋白和某些细胞因子的产生。在本研究中，我们重点研究了BAFF和IFN-γ在IgAN患者中用CpG-ODN刺激TMCs产生伊加中的作用。双色流式细胞术分析显示，从扁桃体新鲜分离的T细胞IFN-γ的细胞间表达在IgAN患者中显著高于非IgAN患者（p=0.032）。伊加和IFN-γ的TMCs的自发产生在IgAN患者中显著高于非IgAN患者（p=0.023和p=0.02）。在CpG-ODN刺激下，IgAN患者TMCs的伊加、BAFF和IFN-γ的产生显著高于非IgAN患者（p=0.013，p=0.005和p=0.039）。用抗BAFF抗体和/或抗IFN-γ抗体处理可抑制CpG-ODN刺激的TMCs产生伊加。在IFN-γ刺激下，IgAN患者CD 1c细胞上的BAFF表达和TMCs的BAFF产生显著高于非IgAN患者（p=0.004和p=0.042）。这些数据表明，IgAN患者中可能存在对微生物DNA的超免疫反应，并可能导致受IFN-γ上调的BAFF过度产生，从而导致IgAN患者中伊加的过度产生。(c)2007年爱思唯尔公司All rights reserved.
IgA nephropathy (IgAN), the most common form of primary glomerulonephritis, is recognized as a tonsil-related diseases since it often gets worse after and/or during acute tonsillitis and the disease progression is often prevented by tonsillectomy. Although several reports showed an increase in IgA production of tonsillar mononuclear cells (TMCs), its mechanism has not yet been fully clarified. Recently, B-cell-activation factor (BAFF), which stimulates B-cell proliferation and immunoglobulin production, was identified. Unmethylated deoxycytidyl-deoxyguanosine oligo-deoxynucleotide (CpG-ODN), which is able to mimic the immunostimulatory activity of microbial DNA, is known to be involved in the production of immunoglobulins and some cytokines. In this study, we focused on roles of BAFF and IFN-gamma in IgA production of TMCs stimulated with CpG-ODN in IgAN patients. Two-color flow cytometric analysis revealed that the intercellular expression of IFN-gamma the T-cells freshly isolated from tonsils was significantly higher in IgAN patients than in non-IgAN patients (p=0.032). The spontaneous productions of IgA and IFN-gamma of TMCs were significantly higher in IgAN patients than in non-IgAN patients (p=0.023 and p=0.02). Under stimulation with CpG-ODN, the productions of IgA, BAFF and IFN-gamma of TMCs were significantly higher in IgAN patients than in non-IgAN patients (p=0.013, p=0.005 and p=0.039). The IgA production of TMCs stimulated by CpG-ODN was inhibited by the treatment with anti-BAFF antibody and/or anti-IFN-gamma antibody. Under stimulation with IFN-gamma, the BAFF expression on the CD1c cells and the BAFF production of TMCs were significantly higher in IgAN patients than in non-IgAN patients (p=0.004 and p=0.042). These data suggest that hyper-immune response to microbial DNA may be present in IgAN patients and may lead to hyperproduction of BAFF up-regutated by IFN-gamma, resulting in hyperproduction of IgA in IgAN patients. (c) 2007 Elsevier Inc. All rights reserved.