Increased IgG4 responses to multiple food and animal antigens indicate a polyclonal expansion and differentiation of pre-existing B cells in IgG4-related disease.

Increased IgG4 responses to multiple food and animal antigens indicate a polyclonal expansion and differentiation of pre-existing B cells in IgG4-related disease.
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DOI:
10.1136/annrheumdis-2014-206405
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发表时间:
2015-05
影响因子:
27.4
通讯作者:
Rispens T
Rispens T
中科院分区:
医学1区
文献类型:
--
作者:
Culver EL;Vermeulen E;Makuch M;van Leeuwen A;Sadler R;Cargill T;Klenerman P;Aalberse RC;van Ham SM;Barnes E;Rispens T

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IgG 4相关疾病(IgG 4-RD)是一种全身性纤维炎性疾病,其特征为血清IgG 4浓度升高和受累器官中大量IgG 4阳性浆细胞。一个重要的问题是IgG 4反应升高是否是病因或疾病的免疫调节机制的反映。通过检查对常见环境抗原的应答,研究IgG 4-RD中的IgG 4应答是否代表普遍的多克隆扩增。通过放射免疫分析法检测了24例IgG 4-RD患者(14例未接受过治疗,10例接受过治疗)、9例原发性硬化性胆管炎和血清IgG 4升高(PSC-高IgG 4)患者以及18例健康对照的血清对鸡蛋白色和蛋黄、牛奶、香蕉、猫、花生、大米和小麦抗原的反应。我们证明了与健康对照相比,IgG 4-RD患者和PSC高IgG 4患者对多种抗原的多克隆IgG 4应答升高。血清IgG 4和抗原特异性反应之间有很强的相关性。与接受过治疗的IgG 4-RD患者相比,未接受过治疗的IgG 4-RD患者对抗原的应答更高。血清电泳和免疫固定显示多克隆性。这是第一项研究,以显示多克隆IgG 4-RD中的多种抗原的增强水平。这支持IgG 4水平升高反映了总体IgG 4应答的异常免疫调节,但不排除疾病的因果关系可能是抗原驱动的。
IgG4-related disease (IgG4-RD) is a systemic fibroinflammatory condition, characterised by an elevated serum IgG4 concentration and abundant IgG4-positive plasma cells in the involved organs. An important question is whether the elevated IgG4 response is causal or a reflection of immune-regulatory mechanisms of the disease. To investigate if the IgG4 response in IgG4-RD represents a generalised polyclonal amplification by examining the response to common environmental antigens. Serum from 24 patients with IgG4-RD (14 treatment-naive, 10 treatment-experienced), 9 patients with primary sclerosing cholangitis and an elevated serum IgG4 (PSC-high IgG4), and 18 healthy controls were tested against egg white and yolk, milk, banana, cat, peanut, rice and wheat antigens by radioimmunoassay. We demonstrated an elevated polyclonal IgG4 response to multiple antigens in patients with IgG4-RD and in PSC-high IgG4, compared with healthy controls. There was a strong correlation between serum IgG4 and antigen-specific responses. Responses to antigens were higher in treatment-naive compared with treatment-experienced patients with IgG4-RD. Serum electrophoresis and immunofixation demonstrated polyclonality. This is the first study to show enhanced levels of polyclonal IgG4 to multiple antigens in IgG4-RD. This supports that elevated IgG4 levels reflect an aberrant immunological regulation of the overall IgG4 response, but does not exclude that causality of disease could be antigen-driven.
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发表时间: 2012-07-23
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发表时间: 2014-02
期刊: Allergy
影响因子: 12.4
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