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COVID-19 中 B-1a 细胞的治疗潜力。

Therapeutic Potential of B-1a Cells in COVID-19.

机构信息

Center for Immunology and Inflammation, The Feinstein Institutes for Medical Research, Manhasset, New York.

Department of Molecular Medicine, Zucker School of Medicine at Hofstra/Northwell, Manhasset, New York.

出版信息

Shock. 2020 Nov;54(5):586-594. doi: 10.1097/SHK.0000000000001610.

Abstract

Coronavirus disease 2019 (COVID-19) is a life-threatening respiratory illness caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Its clinical presentation can vary from the asymptomatic state to acute respiratory distress syndrome (ARDS) and multi-organ dysfunction. Due to our insufficient understanding of its pathophysiology and lack of effective treatment, the morbidity and mortality of severe COVID-19 patients are high. Patients with COVID-19 develop ARDS fueled by exaggerated neutrophil influx into the lungs and cytokine storm. B-1a cells represent a unique subpopulation of B lymphocytes critical for circulating natural antibodies, innate immunity, and immunoregulation. These cells spontaneously produce natural IgM, interleukin (IL)-10, and granulocyte-monocyte colony stimulating factor (GM-CSF). Natural IgM neutralizes viruses and opsonizes bacteria, IL-10 attenuates the cytokine storm, and GM-CSF induces IgM production by B-1a cells in an autocrine manner. Indeed, B-1a cells have been shown to ameliorate influenza virus infection, sepsis, and pneumonia, all of which are similar to COVID-19. The recent discovery of B-1a cells in humans further reinforces their potentially critical role in the immune response against SARS-CoV-2 and their anticipated translational applications against viral and microbial infections. Given that B-1a cells protect against ARDS via immunoglobulin production and the anti-COVID-19 effects of convalescent plasma treatment, we recommend that studies be conducted to further examine the role of B-1a cells in the pathogenesis of COVID-19 and explore their therapeutic potential to treat COVID-19 patients.

摘要

2019 年冠状病毒病(COVID-19)是由新型严重急性呼吸综合征冠状病毒 2(SARS-CoV-2)引起的危及生命的呼吸道疾病。其临床表现可从无症状状态到急性呼吸窘迫综合征(ARDS)和多器官功能障碍。由于我们对其病理生理学的了解不足,以及缺乏有效的治疗方法,严重 COVID-19 患者的发病率和死亡率很高。COVID-19 患者发生 ARDS 的原因是中性粒细胞过度涌入肺部和细胞因子风暴。B-1a 细胞是 B 淋巴细胞的一个独特亚群,对循环天然抗体、固有免疫和免疫调节至关重要。这些细胞自发产生天然 IgM、白细胞介素(IL)-10 和粒细胞-巨噬细胞集落刺激因子(GM-CSF)。天然 IgM 中和病毒并调理细菌,IL-10 减弱细胞因子风暴,GM-CSF 以自分泌方式诱导 B-1a 细胞产生 IgM。事实上,B-1a 细胞已被证明可改善流感病毒感染、败血症和肺炎,所有这些都与 COVID-19 相似。最近在人类中发现 B-1a 细胞进一步证实了它们在针对 SARS-CoV-2 的免疫反应中可能具有关键作用,以及它们在针对病毒和微生物感染的预期转化应用中的作用。鉴于 B-1a 细胞通过免疫球蛋白产生来保护 ARDS,以及恢复期血浆治疗对 COVID-19 的作用,我们建议进行研究,以进一步研究 B-1a 细胞在 COVID-19 发病机制中的作用,并探索其治疗 COVID-19 患者的潜在治疗潜力。

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