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新冠病毒疫苗接种后接受替代治疗的终末期慢性肾病患者中,靶向严重急性呼吸综合征冠状病毒2刺突受体结合域的特异性外周记忆B细胞的动态变化

Dynamics of SARS-CoV-2 Spike Receptor-Binding Domain-Targeted Specific Peripheral Memory B Cells in Patients With End-Stage Chronic Kidney Disease Undergoing Replacement Therapy Following COVID-19 Vaccination.

作者信息

Sánchez-Simarro Ángela, Panizo Nayara, Giménez Estela, Albert Eliseo, Montomoli Marco, Sanchis Irina, Kanter Julia, Górriz José Luis, Navarro David

机构信息

Microbiology Service, Hospital Clínico Universitario de Valencia, INCLIVA Health Research Institute, Valencia, Spain.

Nephrology Service, Hospital Clínico Universitario de Valencia, INCLIVA Health Research Institute, Valencia, Spain.

出版信息

J Med Virol. 2025 May;97(5):e70382. doi: 10.1002/jmv.70382.

Abstract

Memory B cells (MBCs) are responsible for maintaining long-lasting functional B-cell immune responses. Little is known about the kinetics of peripheral blood (PB) SARS-CoV-2 vaccine-induced MBCs in end-stage chronic kidney disease (CKD) patients undergoing replacement therapies. We investigated this issue in this prospective, observational cohort study including 27 patients (9 females and 18 males; median age, 68.4 years, range 48-82) comprising 20 hemodialysis patients and 7 Kidney transplant recipients. SARS-CoV-2-Receptor-Binding Domain (RBD)-targeted PB-MBCs were enumerated by flow cytometry using a tetramer-binding assay after the second COVID-19 mRNA vaccine dose (Post-2D), before (Pre-3D), and after the first mRNA vaccine booster dose (Post-3D). Commercially available electrochemiluminescent immunoassays were used to measure total anti-RBD antibodies targeting an IgG against the S trimeric protein. Overall, 18/27 patients (66.6%) exhibited detectable RBD-MBC responses at Post-2D, 12/27 (44.4%) at Pre-3D, and 16/27 (59.2%) at Post-3D. RBD-MBC levels dropped non-significantly between post-2D and Pre-3D (p = 0.38). A nonsignificant increase in RBD-MBCs was noticed post-3D (p = 0.65). Overall, both antibody specificities displayed the same dynamics but the drop in anti-trimeric spike antibody levels between Post-2D and Pre-3D and increases post-3D were statistically significant (p < 0.001). No correlation (rho = 0.05; p = 0.64) was observed between total antibodies against RBD and RBD-MBC counts. The correlation between IgG antibodies against the trimeric S protein and SARS-CoV-2 RBD-MBC counts was very weak (rho, 0.18; p = 0.11). In summary, waning RBD-MBC counts Pre-3D and increases post-3D are less marked than that of anti-RBD and anti-S trimeric antibodies.

摘要

记忆B细胞(MBCs)负责维持持久的功能性B细胞免疫反应。对于接受替代治疗的终末期慢性肾病(CKD)患者,外周血(PB)中由SARS-CoV-2疫苗诱导产生的MBCs的动力学情况,我们知之甚少。在这项前瞻性观察队列研究中,我们对这一问题展开了调查,该研究纳入了27名患者(9名女性和18名男性;年龄中位数为68.4岁,范围48 - 82岁),其中包括20名血液透析患者和7名肾移植受者。在第二次新冠病毒mRNA疫苗接种剂量后(接种后2天)、第一次mRNA疫苗加强剂量前(接种前3天)以及第一次mRNA疫苗加强剂量后(接种后3天),使用四聚体结合测定法通过流式细胞术对靶向SARS-CoV-2受体结合域(RBD)的PB-MBCs进行计数。使用市售的电化学发光免疫测定法来测量针对S三聚体蛋白的IgG型总抗RBD抗体。总体而言,18/27名患者(66.6%)在接种后2天表现出可检测到的RBD-MBC反应,12/27名患者(44.4%)在接种前3天表现出该反应,16/27名患者(59.2%)在接种后3天表现出该反应。RBD-MBC水平在接种后2天和接种前3天之间无显著下降(p = 0.38)。接种后3天观察到RBD-MBC有不显著的增加(p = 0.65)。总体而言,两种抗体特异性呈现相同的动态变化,但接种后2天和接种前3天之间抗三聚体刺突抗体水平的下降以及接种后3天的增加具有统计学意义(p < 0.001)。针对RBD的总抗体与RBD-MBC计数之间未观察到相关性(rho = 0.05;p = 0.64)。针对三聚体S蛋白的IgG抗体与SARS-CoV-2 RBD-MBC计数之间的相关性非常弱(rho,0.18;p = 0.11)。总之,接种前3天RBD-MBC计数的下降以及接种后3天的增加不如抗RBD和抗S三聚体抗体明显。

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