MDA5-autoimmunity and Interstitial Pneumonitis Contemporaneous with the COVID-19 Pandemic (MIP-C).
MDA5-autoimmunity and Interstitial Pneumonitis Contemporaneous with the COVID-19 Pandemic (MIP-C).
复制标题
MDA5-自身免疫和与 COVID-19 大流行同时发生的间质性肺炎 (MIP-C)。
DOI：
10.1101/2023.11.03.23297727
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发表时间：
2023
期刊：
影响因子：
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通讯作者：
Marzo-O
中科院分区：
文献类型：
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作者：
Iqbal,Khizer;Sinha,Saptarshi;David,Paula;DeMarco,Gabriele;Taheri,Sahar;McLaren,Ella;Maisuria,Sheetal;Arumugakani,Gururaj;Ash,Zoe;Buckley,Catrin;Coles,Lauren;Hettiarachchi,Chamila;Smithson,Gayle;Slade,Maria;Shah,Rahul;Marzo-O
抗MDA5（黑色素瘤分化相关蛋白-5）阳性皮肌炎（MDA5+-DM）的特征是快速进展的间质性肺疾病（ILD）和高死亡率。MDA5感知单链RNA，是SARS-CoV-2病毒的关键模式识别受体。方法：这是一项回顾性观察性研究，在2018年1月至2022年12月期间，在英国约克郡使用15种肌肉特异性自身抗体（msa）小组确定MDA5自身免疫激增。mda5阳性与临床特征和转归、区域SARS-CoV-2阳性和疫苗接种率相关。将COVID-19的基因表达模式与自身免疫性肺病和特发性肺纤维化（IPF）进行比较，以获得观察到的MDA5+-DM爆发的发生线索。结果2020-2022年新增抗mda5 + 60例，其他mda5 +未出现，从2019年的0.4%增加到2020年的2.1%、2021年的4.8%和2022年的1.7%。少数人（8/60）有COVID-19确诊史，2021年的高峰发病率与区域SARS-COV-2社区阳性率重叠，58%（35/60）接受过抗SARS-COV-2 RNA疫苗。少数（8/60）有COVID-19病史，而58%（35/60）接受过抗sars - cov -2 RNA疫苗。60例中有25例发展为ILD，其中8例进展迅速，死亡。在35/60例非ild患者中，14例有肌炎，17例有雷诺现象，10例有皮肌炎谱皮疹。转录组学研究显示，强gifih1（编码MDA5的基因）诱导COVID-19和自身免疫性ILD，但不诱导IPF，并且difih1与以il -15为中心的1型干扰素反应和活化的CD8+ T细胞信号密切相关，这是系统性自身免疫性风湿病背景下进行性ILD的免疫学标志。ifih1rs1990760tt变体减弱了这种反应。结论在COVID-19期间，mda5自身免疫病例与SARS-COV-2病毒的传播同时增加。生物信息学的见解提示一个共同的免疫病理与已知的自身免疫性肺疾病机制。
BackgroundAnti-MDA5 (Melanoma differentiation-associated protein-5) positive dermatomyositis (MDA5+-DM) is characterised by rapidly progressive interstitial lung disease (ILD) and high mortality. MDA5 senses single-stranded RNA and is a key pattern recognition receptor for the SARS-CoV-2 virus.MethodsThis is a retrospective observational study of a surge in MDA5 autoimmunity, as determined using a 15 muscle-specific autoantibodies (MSAs) panel, between Janurary 2018-December 2022 in Yorkshire, UK. MDA5-positivity was correlated with clinical features and outcome, and regional SARS-CoV-2 positivity and vaccination rates. Gene expression patterns in COVID-19 were compared with autoimmune lung disease and idiopathic pulmonary fibrosis (IPF) to gain clues into the genesis of the observed MDA5+-DM outbreak.ResultsSixty new anti-MDA5+, but not other MSAs surged between 2020-2022, increasing from 0.4% in 2019 to 2.1% (2020), 4.8% (2021) and 1.7% (2022). Few (8/60) had a prior history of confirmed COVID-19, peak rates overlapped with regional SARS-COV-2 community positivity rates in 2021, and 58% (35/60) had received anti-SARS-CoV-2 RNA vaccines. Few (8/60) had a prior history of COVID-19, whereas 58% (35/60) had received anti-SARS-CoV-2 RNA vaccines. 25/60 cases developed ILD which rapidly progression with death in 8 cases. Among the 35/60 non-ILD cases, 14 had myositis, 17 Raynaud phenomena and 10 had dermatomyositis spectrum rashes. Transcriptomic studies showed strongIFIH1(gene encoding for MDA5) induction in COVID-19 and autoimmune-ILD, but not IPF, andIFIH1strongly correlated with an IL-15-centric type-1 interferon response and an activated CD8+ T cell signature that is an immunologic hallmark of progressive ILD in the setting of systemic autoimmune rheumatic diseases. TheIFIH1rs1990760TT variant blunted such response.ConclusionsA distinct pattern of MDA5-autoimmunity cases surged contemporaneously with circulation of the SARS-COV-2 virus during COVID-19. Bioinformatic insights suggest a shared immunopathology with known autoimmune lung disease mechanisms.