感染 SARS-CoV-2 的肾移植受者的血液转录组与免疫缺陷的严重程度成正比。
Blood Transcriptomes of SARS-CoV-2-Infected Kidney Transplant Recipients Associated with Immune Insufficiency Proportionate to Severity.
机构信息
Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York.
Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York.
出版信息
J Am Soc Nephrol. 2022 Nov;33(11):2108-2122. doi: 10.1681/ASN.2022010125. Epub 2022 Aug 30.
BACKGROUND
Among patients with COVID-19, kidney transplant recipients (KTRs) have poor outcomes compared with non-KTRs. To provide insight into management of immunosuppression during acute illness, we studied immune signatures from the peripheral blood during and after COVID-19 infection from a multicenter KTR cohort.
METHODS
We ascertained clinical data by chart review. A single sample of blood was collected for transcriptome analysis. Total RNA was poly-A selected and RNA was sequenced to evaluate transcriptome changes. We also measured cytokines and chemokines of serum samples collected during acute infection.
RESULTS
A total of 64 patients with COVID-19 in KTRs were enrolled, including 31 with acute COVID-19 (<4 weeks from diagnosis) and 33 with post-acute COVID-19 (>4 weeks postdiagnosis). In the blood transcriptome of acute cases, we identified genes in positive or negative association with COVID-19 severity scores. Functional enrichment analyses showed upregulation of neutrophil and innate immune pathways but downregulation of T cell and adaptive immune activation pathways. This finding was independent of lymphocyte count, despite reduced immunosuppressant use in most KTRs. Compared with acute cases, post-acute cases showed "normalization" of these enriched pathways after 4 weeks, suggesting recovery of adaptive immune system activation despite reinstitution of immunosuppression. Analysis of the non-KTR cohort with COVID-19 showed significant overlap with KTRs in these functions. Serum inflammatory cytokines followed an opposite trend (, increased with disease severity), indicating that blood lymphocytes are not the primary source.
CONCLUSIONS
The blood transcriptome of KTRs affected by COVID-19 shows decreases in T cell and adaptive immune activation pathways during acute disease that, despite reduced immunosuppressant use, associate with severity. These pathways show recovery after acute illness.
背景
在 COVID-19 患者中，与非肾移植受者（KTR）相比，肾移植受者（KTR）的预后较差。为了深入了解急性疾病期间免疫抑制的管理，我们研究了来自多中心 KTR 队列的 COVID-19 感染期间和之后外周血中的免疫特征。
方法
我们通过病历回顾确定临床数据。采集一份血液样本进行转录组分析。用 poly-A 选择总 RNA，并对 RNA 进行测序以评估转录组变化。我们还测量了急性感染期间采集的血清样本中的细胞因子和趋化因子。
结果
共纳入 64 例 COVID-19 肾移植受者，其中 31 例为急性 COVID-19（诊断后<4 周），33 例为急性后 COVID-19（诊断后>4 周）。在急性病例的血液转录组中，我们鉴定了与 COVID-19 严重程度评分呈正相关或负相关的基因。功能富集分析显示中性粒细胞和固有免疫途径上调，但 T 细胞和适应性免疫激活途径下调。尽管大多数 KTR 减少了免疫抑制剂的使用，但这一发现与淋巴细胞计数无关。与急性病例相比，4 周后，这些富集途径在后急性病例中“正常化”，这表明尽管重新开始使用免疫抑制剂，但适应性免疫系统的激活得到了恢复。对 COVID-19 的非 KTR 队列的分析显示，这些功能与 KTRs 有显著重叠。血清炎症细胞因子则呈相反趋势（随着疾病严重程度的增加而增加），这表明血液淋巴细胞不是主要来源。
结论
受 COVID-19 影响的 KTR 的血液转录组在急性疾病期间表现出 T 细胞和适应性免疫激活途径减少，尽管免疫抑制剂的使用减少，但与严重程度相关。这些途径在急性疾病后得到恢复。
Zotero 插件