Wellcome Sanger Institute, Wellcome Genome Campus, Cambridge, United Kingdom.
Department of Medical Genetics, University of Cambridge, Cambridge, United Kingdom.
Eur J Immunol. 2024 Jan;54(1):e2350633. doi: 10.1002/eji.202350633. Epub 2023 Oct 20.
In COVID-19, hyperinflammatory and dysregulated immune responses contribute to severity. Patients with pre-existing autoimmune conditions can therefore be at increased risk of severe COVID-19 and/or associated sequelae, yet SARS-CoV-2 infection in this group has been little studied. Here, we performed single-cell analysis of peripheral blood mononuclear cells from patients with three major autoimmune diseases (rheumatoid arthritis, psoriasis, or multiple sclerosis) during SARS-CoV-2 infection. We observed compositional differences between the autoimmune disease groups coupled with altered patterns of gene expression, transcription factor activity, and cell-cell communication that substantially shape the immune response under SARS-CoV-2 infection. While enrichment of HLA-DRlow CD14+ monocytes was observed in all three autoimmune disease groups, type-I interferon signaling as well as inflammatory T cell and monocyte responses varied widely between the three groups of patients. Our results reveal disturbed immune responses to SARS-CoV-2 in patients with pre-existing autoimmunity, highlighting important considerations for disease treatment and follow-up.
在 COVID-19 中，过度活跃和失调的免疫反应导致病情加重。因此，患有自身免疫性疾病的患者可能面临更严重的 COVID-19 和/或相关后遗症的风险，然而，针对这一群体的 SARS-CoV-2 感染研究甚少。在这里，我们对三种主要自身免疫性疾病（类风湿关节炎、银屑病或多发性硬化症）患者在 SARS-CoV-2 感染期间的外周血单核细胞进行了单细胞分析。我们观察到自身免疫性疾病组之间存在组成差异，以及基因表达、转录因子活性和细胞间通讯模式的改变，这些改变在 SARS-CoV-2 感染下极大地塑造了免疫反应。尽管在所有三种自身免疫性疾病组中均观察到 HLA-DRlow CD14+单核细胞的富集，但 I 型干扰素信号以及炎症性 T 细胞和单核细胞反应在三组患者之间差异很大。我们的结果揭示了患有自身免疫性疾病的患者对 SARS-CoV-2 的免疫反应失调，强调了疾病治疗和随访的重要考虑因素。
