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风湿肌肉骨骼疾病的免疫抑制剂治疗不会抑制对 SARS-CoV-2 感染的体液反应,并保留效应免疫细胞群体。

Immunosuppressant Treatment in Rheumatic Musculoskeletal Diseases Does Not Inhibit Elicitation of Humoral Response to SARS-CoV-2 Infection and Preserves Effector Immune Cell Populations.

机构信息

Istituto Nazionale Genetica Molecolare, Padiglione Romeo ed Enrica Invernizzi, Milan, Italy.

Ph.D. Program in Translational and Molecular Medicine, Dottorato in Medicina Molecolare e Traslazionale (DIMET), University of Milan-Bicocca, Monza, Italy.

出版信息

Front Immunol. 2022 Jun 10;13:873195. doi: 10.3389/fimmu.2022.873195. eCollection 2022.

Abstract

COVID-19 has proven to be particularly serious and life-threatening for patients presenting with pre-existing pathologies. Patients affected by rheumatic musculoskeletal disease (RMD) are likely to have impaired immune responses against SARS-CoV-2 infection due to their compromised immune system and the prolonged use of disease-modifying anti-rheumatic drugs (DMARDs), which include conventional synthetic (cs) DMARDs or biologic and targeted synthetic (b/ts) DMARDs. To provide an integrated analysis of the immune response following SARS-CoV-2 infection in RMD patients treated with different classes of DMARDs we carried out an immunological analysis of the antibody responses toward SARS-CoV-2 nucleocapsid and RBD proteins and an extensive immunophenotypic analysis of the major immune cell populations. We showed that RMD individuals under most DMARD treatments mount a sustained antibody response to the virus, with neutralizing activity. In addition, they displayed a sizable percentage of effector T and B lymphocytes. Among b-DMARDs, we found that anti-TNFα treatments are more favorable drugs to elicit humoral and cellular immune responses as compared to CTLA4-Ig and anti-IL6R inhibitors. This study provides a whole picture of the humoral and cellular immune responses in RMD patients by reassuring the use of DMARD treatments during COVID-19. The study points to TNF-α inhibitors as those DMARDs permitting elicitation of functional antibodies to SARS-CoV-2 and adaptive effector populations available to counteract possible re-infections.

摘要

COVID-19 对患有既往疾病的患者来说是特别严重和危及生命的。由于免疫系统受损和长期使用疾病修饰抗风湿药物(DMARDs),患有风湿性肌肉骨骼疾病(RMD)的患者可能对 SARS-CoV-2 感染产生免疫应答受损,DMARDs 包括传统合成(cs)DMARDs 或生物和靶向合成(b/ts)DMARDs。为了综合分析接受不同类别 DMARDs 治疗的 RMD 患者感染 SARS-CoV-2 后的免疫反应,我们对针对 SARS-CoV-2 核衣壳和 RBD 蛋白的抗体反应进行了免疫分析,并对主要免疫细胞群进行了广泛的免疫表型分析。我们表明,在大多数 DMARD 治疗下,RMD 个体对病毒产生持续的抗体应答,具有中和活性。此外,他们还显示出相当大比例的效应 T 和 B 淋巴细胞。在 b-DMARDs 中,我们发现与 CTLA4-Ig 和抗 IL6R 抑制剂相比,抗 TNFα 治疗是更有利的药物,可以引发体液和细胞免疫反应。这项研究通过在 COVID-19 期间确保 DMARD 治疗的使用,为 RMD 患者的体液和细胞免疫反应提供了全面的了解。该研究指出 TNF-α 抑制剂是那些允许引发针对 SARS-CoV-2 的功能性抗体和可用的适应性效应细胞群来对抗可能的再感染的 DMARDs。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7ff7/9226581/c14bbe9bbbb2/fimmu-13-873195-g001.jpg

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