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抗SARS-CoV-2疫苗与肌炎相关抗RNA合成酶自身抗体发病率增加的关联。

Association of anti-SARS-COV-2 vaccine with increased incidence of myositis-related anti-RNA-synthetases auto-antibodies.

作者信息

García-Bravo Laura, Calle-Rubio Myriam, Fernández-Arquero Miguel, Mohamed Mohamed Kauzar, Guerra-Galán Teresa, Guzmán-Fulgencio María, Rodríguez de la Peña Antonia, Cañizares Cristina, López Bárbara, Vadillo Cristina, Matías-Guiu Jorge, Nieto Barbero Asunción, Álvarez-Sala Walther José Luis, Sánchez-Ramón Silvia, Ochoa-Grullón Juliana

机构信息

Department of Clinical Immunology and IdSSC, Hospital Clínico San Carlos, Madrid, Spain.

Pneumology and IdSSC, Hospital Clínico San Carlos, Madrid, Spain.

出版信息

J Transl Autoimmun. 2022 Jun 30;5:100160. doi: 10.1016/j.jtauto.2022.100160. eCollection 2022.

Abstract

INTRODUCTION

SARS-CoV-2 is a RNA virus that associates with heterogeneous clinical manifestations and complications. Auto-antibodies are identified in approximately 50% of hospitalized COVID-19 patients.

OBJECTIVES

To determine the global incidence of myositis-related auto-antibodies (non Jo1-RNA synthetases: anti-PL7, anti-PL12, anti-EJ, anti-OJ and RNA-sensor: anti-MDA5) in our laboratory during COVID-19 pandemics, and to describe the clinical and laboratory features of these patients.

STUDY DESIGN

A retrospective study was performed from 2015 to 2021 in a cohort of 444 patients with suspected inflammatory myopathy. The incidence of positive results for the MSA was expressed as absolute value per year for the reference population. Immunoblot analysis, indirect immunofluorescence and HLA typing of 36 patients with positivity for MSAs were collected and analyzed.

RESULTS

We observed MSA positive in 28 patients in 2020 and 36 patients in 2021, representing a mean increase of 6-fold respect to previous years since 2015 (range, 0 to 19). In 2020, the most common antibody detected was anti-MDA5 (68%). In contrast, in 2021 the most common antibodies were anti-PL7 and/or anti-PL12 (69%). All patients in 2021 with positive anti-synthetases were fully vaccinated, 4 had previous documented infection, with median time from vaccine to MSA positivity of 5 months. Eight out of 36 patients (22%) reported clinical onset after SARS-CoV-2 vaccination and 6 out of 36 (17%) presented clinical and/or radiological worsening after SARS-CoV-2 vaccination. All patients presented with a known human leukocyte antigen (HLA)-DRB1* allele associated with ASS. The most prevalent alleles identified were DRB103:01, DRB104, DRB1*11:01, corresponding to 70% (16/23) of our cohort.

CONCLUSIONS

Our preliminary data show an increased incidence of anti-synthetase antibodies during COVID-19 pandemic and SARS-CoV-2 vaccination associated to HLA DRB1* risk allele. Differential profiles of MSA specificities were observed: mainly against RNA-sensors in 2020 and against RNA-synthetases in 2021. Further studies are needed to support the association between SARS-CoV-2 infection and/or vaccination and the occurrence of this autoimmune syndrome.

摘要

引言

严重急性呼吸综合征冠状病毒2(SARS-CoV-2)是一种RNA病毒,可导致多种临床表现和并发症。约50%的住院COVID-19患者可检测到自身抗体。

目的

确定在COVID-19大流行期间,我们实验室中与肌炎相关的自身抗体(非Jo1-RNA合成酶:抗PL7、抗PL12、抗EJ、抗OJ和RNA传感器:抗MDA5)的总体发生率,并描述这些患者的临床和实验室特征。

研究设计

对2015年至2021年期间444例疑似炎性肌病患者进行回顾性研究。将MSA阳性结果的发生率表示为参考人群每年的绝对值。收集并分析了36例MSA阳性患者的免疫印迹分析、间接免疫荧光和HLA分型结果。

结果

我们观察到2020年有28例患者MSA呈阳性,2021年有36例,相较于2015年以来的前几年平均增加了6倍(范围为0至19)。2020年检测到的最常见抗体是抗MDA5(68%)。相比之下,2021年最常见的抗体是抗PL7和/或抗PL12(69%)。2021年所有抗合成酶阳性的患者均已完全接种疫苗,4例有既往感染记录,从接种疫苗到MSA阳性的中位时间为5个月。36例患者中有8例(22%)报告在接种SARS-CoV-2疫苗后出现临床症状,36例中有6例(17%)在接种SARS-CoV-2疫苗后出现临床和/或影像学恶化。所有患者均表现出与抗合成酶综合征(ASS)相关的已知人类白细胞抗原(HLA)-DRB1等位基因。鉴定出的最常见等位基因是DRB103:01、DRB104、DRB111:01,占我们队列的70%(16/23)。

结论

我们的初步数据显示,在COVID-19大流行和SARS-CoV-2疫苗接种期间,抗合成酶抗体的发生率增加,且与HLA DRB1*风险等位基因相关。观察到MSA特异性的不同特征:2020年主要针对RNA传感器,2021年主要针对RNA合成酶。需要进一步研究来支持SARS-CoV-2感染和/或疫苗接种与这种自身免疫综合征发生之间的关联。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe0a/9251718/02f001ad3ec7/gr1.jpg

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