Molecular analysis of B-cell differentiation in selective or partial IgA deficiency
Molecular analysis of B-cell differentiation in selective or partial IgA deficiency
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DOI：
10.1111/j.1365-2249.2004.02440.x
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发表时间：
2004-05-01
影响因子：
4.6
通讯作者：
Kondo, N
中科院分区：
文献类型：
--
作者：
Asano, T;Kaneko, H;Kondo, N
选择性 IgA 缺乏是原发性免疫缺陷最常见的形式，其分子基础尚不清楚。为了调查选择性 IgA 缺乏的原因，我们检查了 B 细胞分化的哪个阶段被阻断。从三名选择性 IgA 缺乏症和三名部分 IgA 缺乏症日本患者中提取 DNA 和 RNA。在选择性 IgA 缺乏症患者中，Iα 种系转录物表达水平下降，并且未检测到 α 环转录物。 PMA 和 TGF-β1 刺激上调 Ialpha 种系和 alpha 环转录本。在一些患者中，抗 CD40、IL-4 和 IL-10 刺激可诱导 IgA 分泌。在部分 IgA 缺乏症患者中，在没有刺激的情况下检测到 Iα 种系、α 环转录物和 Cα 成熟转录物。我们的研究结果表明，类别转换前 Iα 种系转录物表达水平的降低可能对某些选择性 IgA 缺乏症患者的发病机制至关重要。然而，在 IgA 部分缺乏的患者中，类别转换后 B 细胞分化可能会受到干扰。
Selective IgA deficiency is the most common form of primary immunodeficiency, the molecular basis of which is unknown. To investigate the cause of selective IgA deficiency, we examined what stage of B-cell differentiation was blocked. DNA and RNA were extracted from three Japanese patients with selective IgA deficiency and three with a partial IgA deficiency. In selective IgA deficiency patients, Ialpha germline transcript expression levels decreased and alpha circle transcripts were not detected. Stimulation with PMA and TGF-beta1 up-regulated Ialpha germline and alpha circle transcripts. In some patients, IgA secretion was induced by stimulation with anti-CD40, IL-4 and IL-10. In partial IgA deficiency patients, Ialpha germline, alpha circle transcripts and Calpha mature transcripts were detected in the absence of stimulation. Our findings suggest that the decreased expression level of Ialpha germline transcripts before a class switch might be critical for the pathogenesis of some patients with selective IgA deficiency. However, in patients with a partial IgA deficiency, B-cell differentiation might be disturbed after a class switch.