Lu Kun-Lin, Lee Hua-En, Chen Chun-Bing, Hui Rosaline Chung-Yee, Chang Ya-Ching, Lu Chun-Wei, Wang Chuang-Wei, Chung Wen-Hung
Department of Dermatology, Drug Hypersensitivity Clinical and Research Center, Chang Gung Memorial Hospital, Taipei, Keelung, Taiwan.
College of Medicine, Chang Gung University, Taoyuan, Taiwan.
Front Immunol. 2024 Nov 22;15:1506962. doi: 10.3389/fimmu.2024.1506962. eCollection 2024.
Both cellular and humoral responses are important for vaccine protection, but recommendations on immunosuppressants in dermatology are largely based on pre-pandemic experiences. This study aimed to investigate the impacts of immunosuppressants on humoral and cellular immunogenicity to COVID-19 vaccinations in pemphigus patients.
SARS-CoV-2-naïve pemphigus patients and age-, and sex-matched healthy controls were recruited from multiple tertiary medical centers during 2021-2023. Anti-spike protein-related T-cell responses, antibody titers, and high-parameter cell analysis of the peripheral blood were utilized to investigate the inhibitory effects of immunosuppressants, including rituximab and azathioprine.
A total of 32 patients and 120 healthy controls were enrolled. COVID-19 vaccinations spaced at least six months after the last rituximab infusion did not cause a significant difference in anti-viral T-cell or antibody responses between rituximab-naïve and rituximab-treated patients. All pemphigus patients demonstrated improved antibody responses after the third vaccination and none of them suffered from severe COVID-19 illness. Intriguingly, we found that daily dosages of 100 mg or more of azathioprine were linked to significantly decreased anti-viral T-cell responses induced by the vaccination (mean of fold change [SD]; higher azathioprine dosage = 0.70 [0.61] folds vs. lower azathioprine dosage = 2.11 [1.03] folds; = 0.044).
Except for a subset of patients with unrecovered B-cell deficiency, rituximab infusion with proper scheduling of vaccination preserved better anti-viral T-cell responses and did not lead to hindered antibody responses in pemphigus patients. All pemphigus patients benefited from receiving the third booster regardless of B-cell status.
细胞免疫反应和体液免疫反应对疫苗保护均很重要,但皮肤病学中关于免疫抑制剂的建议很大程度上基于疫情前的经验。本研究旨在调查免疫抑制剂对天疱疮患者接种新冠疫苗后体液免疫和细胞免疫原性的影响。
在2021年至2023年期间,从多个三级医疗中心招募了未感染过严重急性呼吸综合征冠状病毒2(SARS-CoV-2)的天疱疮患者以及年龄和性别匹配的健康对照。利用抗刺突蛋白相关的T细胞反应、抗体滴度以及外周血的高参数细胞分析来研究免疫抑制剂(包括利妥昔单抗和硫唑嘌呤)的抑制作用。
共纳入32例患者和120名健康对照。在最后一次输注利妥昔单抗至少六个月后接种新冠疫苗,未感染过SARS-CoV-2的患者和接受过利妥昔单抗治疗的患者在抗病毒T细胞或抗体反应方面没有显著差异。所有天疱疮患者在第三次接种疫苗后抗体反应均有所改善,且无一例发生严重的新冠疾病。有趣的是,我们发现,每日服用100毫克或更多硫唑嘌呤与疫苗诱导的抗病毒T细胞反应显著降低有关(倍数变化均值[标准差];硫唑嘌呤高剂量组=0.70[0.61]倍,硫唑嘌呤低剂量组=2.11[1.03]倍;P=0.044)。
除了一部分B细胞缺陷未恢复的患者外,合理安排疫苗接种时间的利妥昔单抗输注在天疱疮患者中保留了更好的抗病毒T细胞反应,且未导致抗体反应受阻。无论B细胞状态如何,所有天疱疮患者都从接受第三次加强针中获益。