IgE mediated autoallergy against thyroid peroxidase--a novel pathomechanism of chronic spontaneous urticaria?
IgE mediated autoallergy against thyroid peroxidase--a novel pathomechanism of chronic spontaneous urticaria?
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DOI：
10.1371/journal.pone.0014794
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发表时间：
2011-04-12
期刊：
影响因子：
3.7
通讯作者：
Maurer M
中科院分区：
文献类型：
--
作者：
Altrichter S;Peter HJ;Pisarevskaja D;Metz M;Martus P;Maurer M
慢性自发性荨麻疹（csU）的特征是肥大细胞驱动的皮疹和耀斑型皮肤反应的反复发作，通常与总IgE水平升高和甲状腺自身免疫有关。我们推测，一些csU患者表达针对甲状腺抗原（如甲状腺过氧化物酶（TPO））的IgE自身抗体，该抗体可以结合皮肤肥大细胞并诱导其活化。我们开发并使用了一种定点人IgE捕获ELISA来定量IgE-anti- tpo。我们使用该方法对csU患者（n = 478）和健康对照（n = 127）进行了IgE-anti-TPO检测，然后评估了IgE-anti-TPO阳性和阴性csU患者的临床和血清学差异。与健康对照组相比，CsU患者血清中ige -抗tpo水平高出2倍以上（p<0.001）。54%的csU患者血清水平高于临界值（= 5 IU/ml）。通过分布分析，我们确定了两个不同的csU患者亚群：1)IgE-anti-TPOlow （= 39%， IgE-anti-TPO：中位数2.17，四分位数范围0.86-5.44，与健康对照组相当）和2)IgE-anti-TPOhigh （= 61%， IgE-anti-TPO：中位数6.67，四分位数范围5.39-8.24）。ige -anti- tpo阳性和阴性的csU患者在年龄、性别、疾病活动度和病程分布上非常相似。ige -抗tpo阳性的csU患者igg -抗tpo水平和淋巴细胞计数明显升高，C4补体水平明显降低。我们的研究结果表明，相当大的csU患者亚群表达抗甲状腺过氧化物酶的IgE抗体。这些自身抗体可引起“自身过敏性”肥大细胞活化，这是慢性自发性荨麻疹的一种新的病理机制。
Chronic spontaneous urticaria (csU), which is characterized by recurrent episodes of mast cell-driven wheal and flare-type skin reactions, is often associated with elevated total IgE levels and thyroid autoimmunity. We speculate that some csU patients express IgE autoantibodies against thyroid antigens such as thyroid peroxidase (TPO), which could bind to skin mast cells and induce their activation. We developed and used a site-directed human IgE capture ELISA to quantify IgE-anti-TPO. We used this assay and investigated csU patients (n = 478) and healthy control subjects (n = 127) for IgE-anti-TPO and then assessed IgE-anti-TPO-positive and -negative csU patients for clinical and serological differences. CsU patients were found to express more than 2fold higher IgE-anti-TPO serum levels as compared to healthy control subjects (p<0.001). 54% of csU patients had serum levels higher than the cut off ( = 5 IU/ml). By distribution analyses we identified two distinct subpopulations of csU patients: 1) IgE-anti-TPOlow ( = 39%, IgE-anti-TPO: median 2.17 interquartile range 0.86–5.44, = comparable to healthy controls) and 2) IgE-anti-TPOhigh ( = 61%, IgE-anti-TPO: median 6.67, interquartile range 5.39–8.24). IgE-anti-TPO-positive and -negative csU patients had very similar distributions of age and gender as well as disease activity and duration. IgE-anti-TPO-positive csU patients exhibited significantly higher IgG-anti-TPO levels and lymphocyte counts as well as decreased C4 complement levels. Our findings show that a sizeable subgroup of csU patients expresses IgE antibodies against thyroid peroxidase. These autoantibodies could cause “autoallergic” mast cell activation, a novel pathomechanism of chronic spontaneous urticaria.
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