Diminished Diversities and Clonally Expanded Sequences of T-Cell Receptors in Patients with Chronic Spontaneous Urticaria
Xian He,1,2 Xueping Wen,3 Peng Ming He,3 Dan Liang,2 Lihong Yang,2 Yuping Ran,1 Zhixin Zhang3 1Department of Dermatovenereology, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 2Department of Allergy, Chengdu First People’s Hospital, Chengdu, People’s Republic of China;...
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Dove Medical Press
2024-12-01
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| author | He X Wen X He PM Liang D Yang L Ran Y Zhang Z |
| author_facet | He X Wen X He PM Liang D Yang L Ran Y Zhang Z |
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| description | Xian He,1,2 Xueping Wen,3 Peng Ming He,3 Dan Liang,2 Lihong Yang,2 Yuping Ran,1 Zhixin Zhang3 1Department of Dermatovenereology, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 2Department of Allergy, Chengdu First People’s Hospital, Chengdu, People’s Republic of China; 3Chengdu ExAb Biotechnology, LTD, Chengdu, People’s Republic of ChinaCorrespondence: Yuping Ran; Zhixin Zhang, Email ranyuping@vip.sina.com; zhangzhixin@med.uestc.edu.cnObjective: 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.Methods: 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.Results: 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.Conclusion: 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.Keywords: T-cell receptor, T-cell receptor repertoire, T-cell receptor diversity, chronic spontaneous urticaria, high-throughput sequencing |
| format | Article |
| id | doaj-art-8dcfaec0c8fc43ba8b62db0686bb8163 |
| institution | OA Journals |
| issn | 2253-1556 |
| language | English |
| publishDate | 2024-12-01 |
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| series | ImmunoTargets and Therapy |
| spelling | doaj-art-8dcfaec0c8fc43ba8b62db0686bb81632025-08-20T02:31:24ZengDove Medical PressImmunoTargets and Therapy2253-15562024-12-01Volume 1366167198015Diminished Diversities and Clonally Expanded Sequences of T-Cell Receptors in Patients with Chronic Spontaneous UrticariaHe XWen XHe PMLiang DYang LRan YZhang ZXian He,1,2 Xueping Wen,3 Peng Ming He,3 Dan Liang,2 Lihong Yang,2 Yuping Ran,1 Zhixin Zhang3 1Department of Dermatovenereology, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 2Department of Allergy, Chengdu First People’s Hospital, Chengdu, People’s Republic of China; 3Chengdu ExAb Biotechnology, LTD, Chengdu, People’s Republic of ChinaCorrespondence: Yuping Ran; Zhixin Zhang, Email ranyuping@vip.sina.com; zhangzhixin@med.uestc.edu.cnObjective: 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.Methods: 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.Results: 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.Conclusion: 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.Keywords: T-cell receptor, T-cell receptor repertoire, T-cell receptor diversity, chronic spontaneous urticaria, high-throughput sequencinghttps://www.dovepress.com/diminished-diversities-and-clonally-expanded-sequences-of-t-cell-recep-peer-reviewed-fulltext-article-ITTt-cell receptort-cell receptor repertoiret-cell receptor diversitychronic spontaneous urticariahigh-throughput sequencing |
| spellingShingle | He X Wen X He PM Liang D Yang L Ran Y Zhang Z Diminished Diversities and Clonally Expanded Sequences of T-Cell Receptors in Patients with Chronic Spontaneous Urticaria ImmunoTargets and Therapy t-cell receptor t-cell receptor repertoire t-cell receptor diversity chronic spontaneous urticaria high-throughput sequencing |
| title | Diminished Diversities and Clonally Expanded Sequences of T-Cell Receptors in Patients with Chronic Spontaneous Urticaria |
| title_full | Diminished Diversities and Clonally Expanded Sequences of T-Cell Receptors in Patients with Chronic Spontaneous Urticaria |
| title_fullStr | Diminished Diversities and Clonally Expanded Sequences of T-Cell Receptors in Patients with Chronic Spontaneous Urticaria |
| title_full_unstemmed | Diminished Diversities and Clonally Expanded Sequences of T-Cell Receptors in Patients with Chronic Spontaneous Urticaria |
| title_short | Diminished Diversities and Clonally Expanded Sequences of T-Cell Receptors in Patients with Chronic Spontaneous Urticaria |
| title_sort | diminished diversities and clonally expanded sequences of t cell receptors in patients with chronic spontaneous urticaria |
| topic | t-cell receptor t-cell receptor repertoire t-cell receptor diversity chronic spontaneous urticaria high-throughput sequencing |
| url | https://www.dovepress.com/diminished-diversities-and-clonally-expanded-sequences-of-t-cell-recep-peer-reviewed-fulltext-article-ITT |
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