He Xian, Wen Xueping, He Peng Ming, Liang Dan, Yang Lihong, Ran Yuping, Zhang Zhixin
Department of Dermatovenereology, West China Hospital, Sichuan University, Chengdu, People's Republic of China.
Department of Allergy, Chengdu First People's Hospital, Chengdu, People's Republic of China.
Immunotargets Ther. 2024 Dec 5;13:661-671. doi: 10.2147/ITT.S481361. eCollection 2024.
Studies establish a link between autoimmune factors and chronic spontaneous urticaria (CSU). T cells are crucial in immune-mediated diseases like CSU, and T-cell receptor (TCR) diversity could be pivotal in autoimmune responses. The clinical relevance of TCR variations in CSU is unknown, but understanding them may offer insights into CSU's pathogenesis and treatment.
This cross-sectional study included 132 chronic urticaria (CU) patients versus 100 age-matched healthy donors (HD), with subgroup analyses on CU type, angioedema, allergic comorbidities, and anti-IgE therapy efficacy. Peripheral TCRβ repertoires were analyzed by high-throughput sequencing.
CSU patients showed reduced TCR diversity (lower D50) and increased large clone proportions than HD. Moreover, TCR diversity in CSU patients was significantly lower than in those with Chronic Inducible Urticaria (ClndU). There were also differences in variable (V) and joining (J) gene usage between CU and HD groups as well as CSU and ClndU groups. However, in subgroup analyses regarding angioedema, allergic comorbidities, and the efficacy of anti-IgE treatment, no significant differences were found in TCR diversity or large TCRβ clones. Notably, patients with treatment relapse or poor response to anti-IgE therapy had a higher proportion of positively charged CDR3. Additionally, age affected TCR diversity, but TIgE value, EOS counts, CU duration, and UAS7 score did not associate significantly with D50.
CSU patients exhibit reduced TCR diversity and increased large clone proportions, indicating abnormal T cell activation. The TCR diversity differences and distinct V and J gene usage between CSU and ClndU may indicate different mechanisms in T lymphocyte-associated immune responses for these two subtypes of CU. The higher positive charge in CDR3 of relapsed or poorly responsive patients to anti-IGE treatment may indicate more antigen charge involvement. These findings provide new insights into the pathogenesis of CSU and potential future treatments.
研究证实自身免疫因素与慢性自发性荨麻疹（CSU）之间存在联系。T细胞在CSU等免疫介导性疾病中起关键作用，而T细胞受体（TCR）多样性可能在自身免疫反应中起关键作用。CSU中TCR变异的临床相关性尚不清楚，但了解这些变异可能有助于深入了解CSU的发病机制和治疗方法。
这项横断面研究纳入了132例慢性荨麻疹（CU）患者和100例年龄匹配的健康供体（HD），并对CU类型、血管性水肿、过敏性合并症和抗IgE治疗疗效进行了亚组分析。通过高通量测序分析外周血TCRβ库。
与HD相比，CSU患者的TCR多样性降低（D50较低）且大克隆比例增加。此外，CSU患者的TCR多样性显著低于慢性诱导性荨麻疹（ClndU）患者。CU组和HD组以及CSU组和ClndU组之间在可变（V）基因和连接（J）基因的使用上也存在差异。然而，在关于血管性水肿、过敏性合并症和抗IgE治疗疗效的亚组分析中，TCR多样性或大TCRβ克隆未发现显著差异。值得注意的是，治疗复发或对抗IgE治疗反应不佳的患者带正电荷的CDR3比例较高。此外，年龄影响TCR多样性，但TIgE值、嗜酸性粒细胞计数、CU病程和UAS7评分与D50无显著相关性。
CSU患者表现出TCR多样性降低和大克隆比例增加，表明T细胞活化异常。CSU和ClndU之间的TCR多样性差异以及不同的V和J基因使用可能表明这两种CU亚型在T淋巴细胞相关免疫反应中的机制不同。复发或对抗IGE治疗反应不佳的患者CDR3中较高的正电荷可能表明更多的抗原电荷参与。这些发现为CSU的发病机制和未来潜在治疗提供了新的见解。
