新型冠状病毒疫苗引起的即刻过敏和自身免疫性荨麻疹患者免疫反应特征。
Characteristics of immune response profile in patients with immediate allergic and autoimmune urticarial reactions induced by SARS-CoV-2 vaccines.
机构信息
Department of Dermatology, Drug Hypersensitivity Clinical and Research Center, Chang Gung Memorial Hospital, Linkou, Taipei, Tucheng and Keelung, Taiwan; Cancer Vaccine and Immune Cell Therapy Core Laboratory, Chang Gung Memorial Hospital, Linkou, Taiwan; Chang Gung Immunology Consortium, Chang Gung Memorial Hospital and Chang Gung University, Taiwan; Department of Dermatology, Xiamen Chang Gung Hospital, Xiamen, China; College of Medicine, Chang Gung University, Taoyuan, Taiwan.
Department of Dermatology, Drug Hypersensitivity Clinical and Research Center, Chang Gung Memorial Hospital, Linkou, Taipei, Tucheng and Keelung, Taiwan; Chang Gung Immunology Consortium, Chang Gung Memorial Hospital and Chang Gung University, Taiwan; Department of Dermatology, Xiamen Chang Gung Hospital, Xiamen, China; College of Medicine, Chang Gung University, Taoyuan, Taiwan; Immune-Oncology Center of Excellence, Chang Gung Memorial Hospital, Linkou, Taiwan; Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan, School of Medicine, National Tsing Hua University, Hsinchu, Taiwan; Whole-Genome Research Core Laboratory of Human Diseases, Chang Gung Memorial Hospital, Keelung, Taiwan.
出版信息
J Autoimmun. 2023 Jul;138:103054. doi: 10.1016/j.jaut.2023.103054. Epub 2023 May 15.
Severe allergic reactions following SARS-COV-2 vaccination are generally rare, but the reactions are increasingly reported. Some patients may develop prolonged urticarial reactions following SARS-COV-2 vaccination. Herein, we investigated the risk factors and immune mechanisms for patients with SARS-COV-2 vaccines-induced immediate allergy and chronic urticaria (CU). We prospectively recruited and analyzed 129 patients with SARS-COV-2 vaccine-induced immediate allergic and urticarial reactions as well as 115 SARS-COV-2 vaccines-tolerant individuals from multiple medical centers during 2021-2022. The clinical manifestations included acute urticaria, anaphylaxis, and delayed to chronic urticaria developed after SARS-COV-2 vaccinations. The serum levels of histamine, IL-2, IL-4, IL-6, IL-8, IL-17 A, TARC, and PARC were significantly elevated in allergic patients comparing to tolerant subjects (P-values = 4.5 × 10-0.039). Ex vivo basophil revealed that basophils from allergic patients could be significantly activated by SARS-COV-2 vaccine excipients (polyethylene glycol 2000 and polysorbate 80) or spike protein (P-values from 3.5 × 10 to 0.043). Further BAT study stimulated by patients' autoserum showed positive in 81.3% of patients with CU induced by SARS-COV-2 vaccination (P = 4.2 × 10), and the reactions could be attenuated by anti-IgE antibody. Autoantibodies screening also identified the significantly increased of IgE-anti-IL-24, IgG-anti-FcεRI, IgG-anti-thyroid peroxidase (TPO), and IgG-anti-thyroid-related proteins in SARS-COV-2 vaccines-induced CU patients comparing to SARS-COV-2 vaccines-tolerant controls (P-values = 4.6 × 10-0.048). Some patients with SARS-COV-2 vaccines-induced recalcitrant CU patients could be successfully treated with anti-IgE therapy. In conclusion, our results revealed that multiple vaccine components, inflammatory cytokines, and autoreactive IgG/IgE antibodies contribute to SARS-COV-2 vaccine-induced immediate allergic and autoimmune urticarial reactions.
接种 SARS-COV-2 疫苗后发生的严重过敏反应通常很少见，但这种反应的报道越来越多。一些患者在接种 SARS-COV-2 疫苗后可能会出现持续性荨麻疹反应。在此，我们研究了 SARS-COV-2 疫苗引起的即刻过敏和慢性荨麻疹（CU）患者的危险因素和免疫机制。我们前瞻性招募并分析了 2021 年至 2022 年间来自多个医疗中心的 129 例 SARS-COV-2 疫苗引起的即刻过敏和荨麻疹反应患者以及 115 例 SARS-COV-2 疫苗耐受个体。临床表现包括急性荨麻疹、过敏反应和接种 SARS-COV-2 疫苗后迟发性至慢性荨麻疹。与耐受者相比，过敏患者的血清组胺、IL-2、IL-4、IL-6、IL-8、IL-17A、TARC 和 PARC 水平明显升高（P 值分别为 4.5×10-0.039）。体外嗜碱性粒细胞显示，SARS-COV-2 疫苗赋形剂（聚乙二醇 2000 和聚山梨酯 80）或刺突蛋白可显著激活过敏患者的嗜碱性粒细胞（P 值范围为 3.5×10 至 0.043）。进一步的 BAT 研究显示，在 81.3%（4.2×10）的 SARS-COV-2 疫苗接种引起的 CU 患者中，由患者自体血清刺激的 BAT 呈阳性，并且抗 IgE 抗体可减轻反应。自身抗体筛查还发现，与 SARS-COV-2 疫苗耐受对照相比，SARS-COV-2 疫苗接种引起的 CU 患者的 IgE-抗 IL-24、IgG-抗 FcεRI、IgG-抗甲状腺过氧化物酶（TPO）和 IgG-抗甲状腺相关蛋白的水平显著升高（P 值分别为 4.6×10-0.048）。一些 SARS-COV-2 疫苗接种后顽固性 CU 患者可成功接受抗 IgE 治疗。总之，我们的研究结果表明，多种疫苗成分、炎症细胞因子和自身反应性 IgG/IgE 抗体可能导致 SARS-COV-2 疫苗引起的即刻过敏和自身免疫性荨麻疹反应。
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