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贝利尤单抗和/或利妥昔单抗治疗导致的系统性风湿性疾病患者外周血B细胞计数低与新冠病毒-19初种疫苗的抗体反应低有关。

Low Peripheral B-Cell Counts in Patients With Systemic Rheumatic Diseases Due to Treatment With Belimumab and/or Rituximab Are Associated With Low Antibody Responses to Primary COVID-19 Vaccination.

作者信息

Zhang-Sun Jeffrey, Kirou Raphael A, Kirou Kyriakos A

机构信息

Hospital for Special Surgery, New York, NY, USA.

SUNY Downstate Medical School, New York, NY, USA.

出版信息

HSS J. 2023 May;19(2):180-186. doi: 10.1177/15563316221142846. Epub 2022 Dec 16.

DOI:10.1177/15563316221142846
PMID:37051614
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9760510/
Abstract

Immunosuppressive agents inhibit COVID-19 vaccine antibody (Ab) responses in patients with systemic rheumatic diseases. Rituximab may fully block Ab responses when B cells become undetected. The effect of detected but low number of B cells due to treatment with a B-cell agent (belimumab and/or rituximab) has not been established. : We sought to examine whether there is an association between a low number of B cells due to treatment with belimumab and/or rituximab and impaired primary COVID-19 vaccination spike Ab responses in patients with systemic rheumatic diseases. : We retrospectively examined Ab responses to COVID-19 vaccinations, especially in relation to B-cell counts after treatment with belimumab and/or rituximab, in 58 patients with systemic rheumatic diseases: 22 on and 36 not on B-cell agents. We used Kruskal-Wallis and Mann-Whitney tests for comparison of Ab values between the groups and Fisher exact test for relative risk calculations. : Median (interquartile range) postvaccination Ab responses were lower in patients on versus those not on B-cell agents: 3.91 (0.77-20.00) versus 20.00 (14.32-20.00), respectively. Among patients on belimumab and/or rituximab, Ab responses of less than 25% of the assay's upper limit were exclusively observed in those with B-cell counts lower than 40/µL. Patients with B-cell counts lower than 40/µL exhibit a relative risk of 6.092 (95% CI: 2.75-14.24) for Ab responses of less than 25% of the upper limit compared with patients not on B-cell agents. This relative risk remained significant, even after excluding patients with undetected B cells. : This retrospective study found an association between low B-cell counts (less than 40/µL) and decreased Ab responses to primary COVID-19 vaccination in patients with systemic rheumatic diseases treated with belimumab and/or rituximab. Despite the small number of patients studied, these findings add to the accumulating evidence on the importance of B-cell count in predicting spike Ab responses to COVID-19 vaccination.

摘要

免疫抑制剂会抑制系统性风湿疾病患者对新冠疫苗的抗体反应。当检测不到B细胞时,利妥昔单抗可能会完全阻断抗体反应。使用B细胞药物(贝利尤单抗和/或利妥昔单抗)治疗导致B细胞数量检测到但较少的影响尚未明确。我们试图研究因使用贝利尤单抗和/或利妥昔单抗治疗导致B细胞数量较少与系统性风湿疾病患者初次接种新冠疫苗后刺突抗体反应受损之间是否存在关联。我们回顾性研究了58例系统性风湿疾病患者对新冠疫苗的抗体反应,特别是与使用贝利尤单抗和/或利妥昔单抗治疗后的B细胞计数的关系,其中22例正在使用B细胞药物,36例未使用。我们使用Kruskal-Wallis检验和Mann-Whitney检验比较组间抗体值,并使用Fisher精确检验计算相对风险。接种疫苗后的抗体反应中位数(四分位间距)在使用B细胞药物的患者中低于未使用的患者:分别为3.91(0.77 - 20.00)和20.00(14.32 - 20.00)。在使用贝利尤单抗和/或利妥昔单抗的患者中,仅在B细胞计数低于40/µL的患者中观察到抗体反应低于检测上限的25%。与未使用B细胞药物的患者相比,B细胞计数低于40/µL的患者抗体反应低于上限25%的相对风险为6.092(95%CI:2.75 - 14.24)。即使排除检测不到B细胞的患者,这种相对风险仍然显著。这项回顾性研究发现,在使用贝利尤单抗和/或利妥昔单抗治疗的系统性风湿疾病患者中,低B细胞计数(低于40/µL)与初次接种新冠疫苗后的抗体反应降低之间存在关联。尽管研究的患者数量较少,但这些发现进一步证明了B细胞计数在预测新冠疫苗刺突抗体反应中的重要性,相关证据不断积累。

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本文引用的文献

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J Clin Rheumatol. 2023 Mar 1;29(2):109-111. doi: 10.1097/RHU.0000000000001907. Epub 2022 Sep 20.
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Immunogenicity and safety of a fourth COVID-19 vaccination in rituximab-treated patients: an open-label extension study.利妥昔单抗治疗患者中第四剂 COVID-19 疫苗的免疫原性和安全性:一项开放性扩展研究。
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American College of Rheumatology Guidance for COVID-19 Vaccination in Patients With Rheumatic and Musculoskeletal Diseases: Version 4.美国风湿病学会风湿和肌肉骨骼疾病患者 COVID-19 疫苗接种指南:第 4 版。
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