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严重急性呼吸综合征冠状病毒2(SARS-CoV-2)信使核糖核酸(mRNA)疫苗接种后出现包括关节外表现的类风湿关节炎发作病例系列:全面细胞因子检测

A Case Series of Rheumatoid Arthritis Flare Including Extra-articular Manifestations Following SARS-CoV-2 mRNA Vaccination: A Comprehensive Cytokine Assay.

作者信息

Iwamura Narumichi, Eguchi Katusmi, Takatani Ayuko, Tsutsumi Kanako, Koga Tomohiro, Araki Takeshi, Aramaki Toshiyuki, Terada Kaoru, Ueki Yukitaka

机构信息

Department of Internal Medicine, Sasebo Chuo Hospital, Sasebo, JPN.

Department of Rheumatology, Sasebo Chuo Hospital, Sasebo, JPN.

出版信息

Cureus. 2024 Apr 22;16(4):e58740. doi: 10.7759/cureus.58740. eCollection 2024 Apr.

Abstract

INTRODUCTION

The administration of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccines has played a pivotal role in managing the COVID-19 pandemic. Nonetheless, there have been instances of atypical immune reactions to the vaccine, notably among patients with autoimmune inflammatory rheumatic diseases such as rheumatoid arthritis (RA).

AIM

This study was designed to analyze the cytokine profiles of RA patients who suffered from severe or fatal disease flares after receiving the SARS-CoV-2 mRNA vaccine, to unravel the immunological bases for such responses.

METHODS

We conducted a retrospective observational study involving three RA patients. These individuals had their disease under control prior to experiencing severe disease flares post-mRNA vaccination. A detailed serum cytokine analysis was carried out and compared with that of a healthy control group.

RESULTS

Post-vaccination, each patient displayed a marked cytokine storm, with notably increased levels of IL-1β (342, 109, and 27.5 pg/mL, respectively), IL-6 (67.8, 82.7, and 201 pg/mL, respectively), IL-17A (172, 51.6, and 30.3 pg/mL, respectively), and TNF-α (279, 97.5, and 59.4 pg/mL, respectively). Two patients responded well to treatment with biological and synthetic DMARDs, including baricitinib and abatacept. Unfortunately, one patient passed away even after receiving tocilizumab.

CONCLUSION

The findings from the comprehensive cytokine assays indicate severe cytokine abnormalities, pointing to cytokine storm syndrome. This suggests that SARS-CoV-2 mRNA vaccination may trigger a disruption in immune homeostasis, potentially leading to the acute worsening of pulmonary complications in RA patients, even those with previously low disease activity. It's necessary to weigh the risks of severe outcomes from COVID-19 against the potential for flares or other adverse reactions following vaccination. Such risk assessments should take into account the individual patient's health status, existing conditions, and other risk factors. Close follow-up after vaccination is crucial, especially for patients with RA.

摘要

引言

严重急性呼吸综合征冠状病毒2(SARS-CoV-2)mRNA疫苗的接种在应对新冠疫情中发挥了关键作用。尽管如此,仍有疫苗非典型免疫反应的情况出现,尤其是在患有自身免疫性炎性风湿性疾病(如类风湿关节炎(RA))的患者中。

目的

本研究旨在分析接种SARS-CoV-2 mRNA疫苗后出现严重或致命疾病发作的RA患者的细胞因子谱,以揭示此类反应的免疫基础。

方法

我们进行了一项回顾性观察研究,涉及三名RA患者。这些患者在mRNA疫苗接种后出现严重疾病发作之前,病情处于控制状态。进行了详细的血清细胞因子分析,并与健康对照组进行了比较。

结果

接种疫苗后,每位患者均出现明显的细胞因子风暴,白细胞介素-1β(分别为342、109和27.5 pg/mL)、白细胞介素-6(分别为67.8、82.7和201 pg/mL)、白细胞介素-17A(分别为172、51.6和30.3 pg/mL)和肿瘤坏死因子-α(分别为279、97.5和59.4 pg/mL)水平显著升高。两名患者对包括巴瑞替尼和阿巴西普在内的生物和合成抗风湿药物治疗反应良好。不幸的是,一名患者即使接受了托珠单抗治疗仍去世。

结论

全面细胞因子检测的结果表明存在严重的细胞因子异常,提示细胞因子风暴综合征。这表明SARS-CoV-2 mRNA疫苗接种可能引发免疫稳态破坏,甚至可能导致RA患者(即使是先前疾病活动度较低的患者)肺部并发症急性恶化。有必要权衡新冠病毒感染导致严重后果的风险与接种疫苗后出现疾病发作或其他不良反应的可能性。此类风险评估应考虑个体患者的健康状况、现有疾病及其他风险因素。接种疫苗后密切随访至关重要,尤其是对于RA患者。

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