Department of Dermatology and Allergy, Allergie-Centrum-Charité/ECARF, Charité-Universitätsmedizin Berlin, Berlin, Germany.
PLoS One. 2011 Apr 12;6(4):e14794. doi: 10.1371/journal.pone.0014794.
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-TPO(low) ( = 39%, IgE-anti-TPO: median 2.17 interquartile range 0.86-5.44, = comparable to healthy controls) and 2) IgE-anti-TPO(high) ( = 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.
慢性自发性荨麻疹（csU）的特征是反复发作的肥大细胞驱动的风团和红斑型皮肤反应，常伴有总 IgE 水平升高和甲状腺自身免疫。我们推测，一些 csU 患者表达针对甲状腺抗原的 IgE 自身抗体，如甲状腺过氧化物酶（TPO），这些抗体可能与皮肤肥大细胞结合并诱导其激活。
我们开发并使用了一种定向人 IgE 捕获 ELISA 来定量 IgE-抗 TPO。我们使用该检测方法检测了 478 例 csU 患者和 127 例健康对照者的 IgE-抗 TPO，并评估了 IgE-抗 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 患者的血清 IgE-抗 TPO 水平高出 2 倍以上（p<0.001）。54%的 csU 患者的血清水平高于截断值（=5 IU/ml）。通过分布分析，我们确定了两种不同的 csU 患者亚群：1）IgE-抗 TPO（低）（=39%，IgE-抗 TPO：中位数 2.17，四分位距 0.86-5.44，=与健康对照组相当）和 2）IgE-抗 TPO（高）（=61%，IgE-抗 TPO：中位数 6.67，四分位距 5.39-8.24）。IgE-抗 TPO 阳性和阴性 csU 患者的年龄和性别分布、疾病活动度和持续时间非常相似。IgE-抗 TPO 阳性 csU 患者的 IgG-抗 TPO 水平、淋巴细胞计数显著升高，C4 补体水平降低。
我们的研究结果表明，相当大一部分 csU 患者表达针对甲状腺过氧化物酶的 IgE 抗体。这些自身抗体可能导致“自身过敏性”肥大细胞激活，这是慢性自发性荨麻疹的一种新的发病机制。
