METHODS: We used COVID-19 vaccination as a model to investigate vaccine-induced IgG subclass levels and Fc glycosylation patterns, B cell subsets, and effector functions of short- and long-term Ab responses after up to three vaccinations in patients on anti-TNF or other immunosuppressive treatments and in healthy individuals. Using TriNetX, a global healthcare database, we determined the risk of SARS-CoV-2 breakthrough infections in vaccinated patients treated with anti-TNF or other immunosuppressive drugs.
RESULTS: Anti-TNF treatment reduced the long-term abundance of all anti-S IgG subclasses with low levels of galactosylation and sialylation. Re-activation of potential memory B cells initially generated highly galactosylated and sialylated IgG antibodies, which were progressively reduced after each booster dose in anti-TNF-treated patients, especially in the elderly. The reduced short- and long-term IgG (1) levels in anti-TNF-treated patients correlated with diminished functional activity and an increased risk for the development of COVID-19.
CONCLUSIONS: The data suggest that anti-TNF treatment reduces both GC-dependent long-lived PCs and GC-dependent memory B cell-derived short-lived PCs, hence both the long- and short-term IgG subclass responses, respectively, after repeated vaccination. We propose that anti-TNF therapy, especially in the elderly, reduces the benefit of booster vaccination.
方法:我们使用COVID-19疫苗作为模型来研究疫苗诱导的IgG亚类水平和Fc糖基化模式,B细胞亚群,在接受抗TNF或其他免疫抑制治疗的患者和健康个体中,接种多达三次疫苗后,短期和长期Ab反应的效应子功能。使用TriNetX,全球医疗保健数据库,我们确定了接受抗TNF或其他免疫抑制药物治疗的疫苗接种患者发生SARS-CoV-2突破性感染的风险.
结果:抗TNF治疗降低了所有抗SIgG亚类的长期丰度,半乳糖基化和唾液酸化水平较低。重新激活潜在的记忆B细胞最初产生高度半乳糖基化和唾液酸化的IgG抗体,在抗TNF治疗的患者中,每次加强剂量后逐渐减少,尤其是老年人。抗TNF治疗患者的短期和长期IgG(1)水平降低与功能活性降低和COVID-19发展风险增加相关。
结论:数据表明,抗TNF治疗既减少了GC依赖性长寿命PCs,也减少了GC依赖性记忆B细胞衍生的短寿命PCs,因此,长期和短期的IgG亚类反应,分别,反复接种疫苗后。我们建议抗TNF治疗,尤其是老年人,减少加强疫苗接种的好处。