PDF(Pubmed)
Abstract：
SARS-CoV-2 vaccination in rheumatoid arthritis (RA) patients treated with B cell-depleting drugs induced limited seroconversion but robust cellular response. We aimed to document specific T and B cell immunity in response to vaccine booster doses and breakthrough infection (BTI).
We included 76 RA patients treated with rituximab who received up to four SARS-CoV-2 vaccine doses or three doses plus BTI, in addition to vaccinated healthy donors (HD) and control patients treated with tumor necrosis factor inhibitor (TNFi). We quantified anti-SARS-CoV-2 receptor-binding domain (RBD) Spike IgG, anti-nucleocapsid (NC) IgG, 92 circulating inflammatory proteins, Spike-binding B cells, and Spike-specific T cells along with comprehensive high-dimensional phenotyping and functional assays.
The time since the last rituximab infusion, persistent inflammation, and age were associated with the anti-SARS-CoV-2 RBD IgG seroconversion. The vaccine-elicited serological response was accompanied by an incomplete induction of peripheral Spike-specific memory B cells but occurred independently of T cell responses. Vaccine- and BTI-elicited cellular immunity was similar between RA and HD ex vivo in terms of frequency or phenotype of Spike-specific cytotoxic T cells and in vitro in terms of the functionality and differentiation profile of Spike-specific T cells.
SARS-CoV-2 vaccination in RA can induce persistent effector T-cell responses that are reactivated by BTI. Paused rituximab medication allowed serological responses after a booster dose (D4), especially in RA with lower inflammation, enabling efficient humoral and cellular immunity after BTI, and contributed overall to the development of potential durable immunity.
We included 76 RA patients treated with rituximab who received up to four SARS-CoV-2 vaccine doses or three doses plus BTI, in addition to vaccinated healthy donors (HD) and control patients treated with tumor necrosis factor inhibitor (TNFi). We quantified anti-SARS-CoV-2 receptor-binding domain (RBD) Spike IgG, anti-nucleocapsid (NC) IgG, 92 circulating inflammatory proteins, Spike-binding B cells, and Spike-specific T cells along with comprehensive high-dimensional phenotyping and functional assays.
The time since the last rituximab infusion, persistent inflammation, and age were associated with the anti-SARS-CoV-2 RBD IgG seroconversion. The vaccine-elicited serological response was accompanied by an incomplete induction of peripheral Spike-specific memory B cells but occurred independently of T cell responses. Vaccine- and BTI-elicited cellular immunity was similar between RA and HD ex vivo in terms of frequency or phenotype of Spike-specific cytotoxic T cells and in vitro in terms of the functionality and differentiation profile of Spike-specific T cells.
SARS-CoV-2 vaccination in RA can induce persistent effector T-cell responses that are reactivated by BTI. Paused rituximab medication allowed serological responses after a booster dose (D4), especially in RA with lower inflammation, enabling efficient humoral and cellular immunity after BTI, and contributed overall to the development of potential durable immunity.
摘要：
■在用B细胞消耗药物治疗的类风湿关节炎（RA）患者中，SARS-CoV-2疫苗可诱导有限的血清转化，但细胞反应强烈。我们旨在记录对疫苗加强剂量和突破性感染（BTI）的特异性T和B细胞免疫。
■我们纳入了76名接受利妥昔单抗治疗的RA患者，他们接受了多达四剂SARS-CoV-2疫苗或三剂BTI，除了接种疫苗的健康供体（HD）和接受肿瘤坏死因子抑制剂（TNFi）治疗的对照患者。我们定量了抗SARS-CoV-2受体结合域（RBD）尖峰IgG，抗核衣壳（NC）IgG，92个循环炎性蛋白，刺突结合B细胞，和Spike特异性T细胞以及全面的高维表型和功能测定。
■自上次利妥昔单抗输注以来的时间，持续性炎症,年龄与抗SARS-CoV-2RBDIgG血清转换有关。疫苗引发的血清学反应伴随着外周尖峰特异性记忆B细胞的不完全诱导，但与T细胞反应无关。就Spike特异性细胞毒性T细胞的频率或表型以及体外Spike特异性T细胞的功能和分化谱而言，疫苗和BTI引起的细胞免疫在离体RA和HD之间相似。
■在RA中接种SARS-CoV-2可以诱导被BTI重新激活的持续效应T细胞应答。暂停的利妥昔单抗药物允许加强剂量后的血清学反应（D4），尤其是在炎症较低的RA中，在BTI之后实现有效的体液和细胞免疫，总体上促进了潜在持久免疫力的发展。
■我们纳入了76名接受利妥昔单抗治疗的RA患者，他们接受了多达四剂SARS-CoV-2疫苗或三剂BTI，除了接种疫苗的健康供体（HD）和接受肿瘤坏死因子抑制剂（TNFi）治疗的对照患者。我们定量了抗SARS-CoV-2受体结合域（RBD）尖峰IgG，抗核衣壳（NC）IgG，92个循环炎性蛋白，刺突结合B细胞，和Spike特异性T细胞以及全面的高维表型和功能测定。
■自上次利妥昔单抗输注以来的时间，持续性炎症,年龄与抗SARS-CoV-2RBDIgG血清转换有关。疫苗引发的血清学反应伴随着外周尖峰特异性记忆B细胞的不完全诱导，但与T细胞反应无关。就Spike特异性细胞毒性T细胞的频率或表型以及体外Spike特异性T细胞的功能和分化谱而言，疫苗和BTI引起的细胞免疫在离体RA和HD之间相似。
■在RA中接种SARS-CoV-2可以诱导被BTI重新激活的持续效应T细胞应答。暂停的利妥昔单抗药物允许加强剂量后的血清学反应（D4），尤其是在炎症较低的RA中，在BTI之后实现有效的体液和细胞免疫，总体上促进了潜在持久免疫力的发展。
