Characteristics of immune response profile in patients with immediate allergic and autoimmune urticarial reactions induced by SARS-CoV-2 vaccines

Chuang-Wei Wang; Chun-Bing Chen; Chun-Wei Lu; Wei-Ti Chen; Rosaline Chung-Yee Hui; Tsu-Man Chiu; Min-Hui Chi; Jing-Chi Lin; Yu-Huei Huang; Ya-Ching Chang; Jennifer Wu; Kuan-Yu Chen; Yang Yu-Wei Lin; Tzong-Yun Ger; Jing Yi Lin; Wan-Ting Tsai; Yen-Ju Pan; Wen-Hung Chung

doi:10.1016/j.jaut.2023.103054

Characteristics of immune response profile in patients with immediate allergic and autoimmune urticarial reactions induced by SARS-CoV-2 vaccines

J Autoimmun. 2023 Jul:138:103054. doi: 10.1016/j.jaut.2023.103054. Epub 2023 May 15.

Authors

Chuang-Wei Wang¹, Chun-Bing Chen², Chun-Wei Lu³, Wei-Ti Chen⁴, Rosaline Chung-Yee Hui⁵, Tsu-Man Chiu⁶, Min-Hui Chi⁷, Jing-Chi Lin⁸, Yu-Huei Huang⁵, Ya-Ching Chang⁵, Jennifer Wu⁹, Kuan-Yu Chen⁵, Yang Yu-Wei Lin¹⁰, Tzong-Yun Ger⁵, Jing Yi Lin⁵, Wan-Ting Tsai¹⁰, Yen-Ju Pan¹⁰, Wen-Hung Chung¹¹

Affiliations

¹ 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.
² 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.
³ Department of Dermatology, Drug Hypersensitivity Clinical and Research Center, Chang Gung Memorial Hospital, Linkou, Taipei, Tucheng and Keelung, 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.
⁴ Department of Dermatology, Drug Hypersensitivity Clinical and Research Center, Chang Gung Memorial Hospital, Linkou, Taipei, Tucheng and Keelung, Taiwan; Department of Dermatology, Xiamen Chang Gung Hospital, Xiamen, China; College of Medicine, Chang Gung University, Taoyuan, Taiwan.
⁵ Department of Dermatology, Drug Hypersensitivity Clinical and Research Center, Chang Gung Memorial Hospital, Linkou, Taipei, Tucheng and Keelung, Taiwan; College of Medicine, Chang Gung University, Taoyuan, Taiwan.
⁶ Department of Dermatology, Chung Shan Medical University Hospital, Taichung, Taiwan; Institute of Medicine, School of Medicine, Chung Shan Medical University, Taichung, Taiwan.
⁷ Department of Dermatology, Drug Hypersensitivity Clinical and Research Center, Chang Gung Memorial Hospital, Linkou, Taipei, Tucheng and Keelung, Taiwan; College of Medicine, Chang Gung University, Taoyuan, Taiwan; Institute of Molecular Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan.
⁸ College of Medicine, Chang Gung University, Taoyuan, Taiwan; Division of Allergy Immunology and Rheumatology, Chang Gung Memorial Hospital, Chiayi, Taiwan.
⁹ Department of Dermatology, Drug Hypersensitivity Clinical and Research Center, Chang Gung Memorial Hospital, Linkou, Taipei, Tucheng and Keelung, Taiwan; College of Medicine, Chang Gung University, Taoyuan, Taiwan; Immune-Oncology Center of Excellence, Chang Gung Memorial Hospital, Linkou, Taiwan.
¹⁰ Department of Dermatology, Drug Hypersensitivity Clinical and Research Center, Chang Gung Memorial Hospital, Linkou, Taipei, Tucheng and Keelung, Taiwan.
¹¹ 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; Immune-Oncology Center of Excellence, Chang Gung Memorial Hospital, Linkou, Taiwan; Whole-Genome Research Core Laboratory of Human Diseases, Chang Gung Memorial Hospital, Keelung, Taiwan; Department of Dermatology, Beijing Tsinghua Chang Gung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China; Department of Dermatology, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China; Genomic Medicine Core Laboratory, Chang Gung Memorial Hospital, Linkou, Taiwan. Electronic address: wenhungchung@yahoo.com.

Abstract

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^-5-0.039). 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^-4 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^-13), 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^-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.

Keywords: Anti-TPO IgG; Autoreactive antibodies; Chronic urticaria; PEG; SARS-COV-2 vaccine.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

COVID-19 Vaccines / adverse effects
COVID-19*
Chronic Urticaria* / metabolism
Humans
Immunity
Immunoglobulin G
SARS-CoV-2
Urticaria* / diagnosis
Vaccination

Substances

COVID-19 Vaccines
Immunoglobulin G