Institute of Allergology, Charité - Universitätsmedizin Berlin, Berlin, Germany.
Fraunhofer Institute for Translational Medicine and Pharmacology (ITMP), Allergology and Immunology, Berlin, Germany.
Front Immunol. 2022 Jul 19;13:902652. doi: 10.3389/fimmu.2022.902652. eCollection 2022.
The pathogenesis of chronic spontaneous urticaria (CSU) has not been clarified entirely. Type IIb autoimmune chronic spontaneous urticaria (CSU) is a distinct subtype of CSU that is often difficult to treat and is connected to low levels of total IgE. Previous findings indicate that an enhanced signal transducer and activator of transcription 3 (STAT3) may be responsible for reduced IgE serum levels.
Our aim was to investigate a possible underlying gain-of-function mutation or activating polymorphism in that could be responsible for the low levels of IgE in patients with CSU.
We included 10 patients with CSU and low levels of IgE and sequenced selected single nucleotide polymorphisms (SNP) in associated with common autoimmune diseases. Exon sequencing was performed for the most relevant exons of . To test for a gain-of-function of STAT3, we performed a phospho-specific flow cytometry analysis of STAT3 in peripheral blood mononuclear cells before and after stimulation with interleukin-6.
No differences were found in the prevalence of the tested SNPs between our patients and a control population. Moreover, we could not find any mutations or variants on the tested exons of . The function of STAT3 was also not altered in our patients.
In total, we could not find any evidence for our hypothesis that low IgE in patients with CSU is linked to mutations in or altered activity of STAT3. Thus, it remains to be discovered what causes the low serum levels of IgE in patients with CSU.
慢性自发性荨麻疹（CSU）的发病机制尚未完全阐明。Ⅱb 型自身免疫性慢性自发性荨麻疹（CSU）是 CSU 的一个独特亚型，通常难以治疗，且与总 IgE 水平降低有关。先前的研究结果表明，增强的信号转导子和转录激活子 3（STAT3）可能是导致 IgE 血清水平降低的原因。
我们旨在研究导致 CSU 患者 IgE 水平降低的 是否存在潜在的功能获得性突变或激活多态性。
我们纳入了 10 例 IgE 水平降低的 CSU 患者，并对与常见自身免疫性疾病相关的 中的选定单核苷酸多态性（SNP）进行测序。对 中最相关的外显子进行外显子测序。为了检测 STAT3 是否具有功能获得性，我们在白细胞介素-6 刺激前后对患者外周血单个核细胞中的 STAT3 进行磷酸化特异性流式细胞术分析。
我们未发现患者中检测到的 SNP 的患病率与对照组之间存在差异。此外，我们在测试的 外显子上也没有发现任何突变或变异。我们患者的 STAT3 功能也没有改变。
总之，我们没有发现任何证据支持我们的假设，即 CSU 患者的低 IgE 与 中的突变或 STAT3 活性改变有关。因此，CSU 患者 IgE 血清水平降低的原因仍有待发现。
