Emergency Lung Transplantation after COVID-19: Immunopathological Insights on Two Affected Patients.
Emergency Lung Transplantation after COVID-19: Immunopathological Insights on Two Affected Patients.
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DOI：
10.3390/cells10030611
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发表时间：
2021-03-10
期刊：
影响因子：
6
通讯作者：
Ferrero S
中科院分区：
文献类型：
--
作者：
Croci GA;Vaira V;Trabattoni D;Biasin M;Valenti L;Baselli G;Barberis M;Guerini Rocco E;Gregato G;Scandroglio M;Fominskiy E;Palleschi A;Rosso L;Nosotti M;Clerici M;Ferrero S
我们在此描述了两名接受双侧肺移植（bLTx）的意大利COVID-19患者的免疫病理学特征。对取出的肺进行组织病理学评价。对肺标本和SARS-CoV-2刺激的外周血单核细胞（PBMC）进行免疫相关特征的基因表达谱（GEP）分析。测量肺、支气管肺泡灌洗液和培养上清液中的细胞因子水平。病理学评估显示广泛的肺损伤，具有增殖至纤维化阶段的模式，弥漫性肺泡损伤类似于普通型间质性肺炎（UIP）。肺GEP显示病原体识别受体、效应细胞因子和趋化因子、免疫激活受体和炎性体组分的过表达。多重细胞因子分析证实了促炎状态，单核细胞/巨噬细胞趋化和活化因子以及IL-6和TNF-α水平较高。在移植后7天收集的SARS-CoV-2刺激的PBMC中观察到类似的特征。在肺部观察到的组织损伤模式表明，这可能代表了长期疾病的输出，类似于弥漫性UIP样图像。分子免疫分析支持持续性促炎状态和持续体液免疫的范例，尽管存在医源性免疫抑制，但仍维持这些状态。
We herein characterize the immunopathological features of two Italian COVID-19 patients who underwent bilateral lung transplantation (bLTx). Removed lungs underwent histopathological evaluation. Gene expression profiling (GEP) for immune-related signatures was performed on lung specimens and SARS-CoV-2-stimulated peripheral blood mononuclear cells (PBMCs). Cytokine levels were measured on lungs, bronchoalveolar lavage fluids and in culture supernatants. Pathological assessment showed extensive lung damage with the pattern of proliferative to fibrotic phases, with diffuse alveolar damage mimicking usual interstitial pneumonia (UIP). Lungs’ GEP revealed overexpression of pathogen recognition receptors, effector cytokines and chemokines, immune activation receptors and of the inflammasome components. Multiplex cytokine analysis confirmed a proinflammatory state, with high levels of monocyte/macrophage chemotactic and activating factors and of IL-6 and TNF-α. A similar profile was observed in SARS-CoV-2-stimulated PBMCs collected 7 days after transplant. The pattern of tissue damage observed in the lungs suggests that this may represent the output of protracted disease, resembling a diffuse UIP-like picture. The molecular immune profiling supports the paradigm of a persistent proinflammatory state and sustained humoral immunity, conditions that are maintained despite the iatrogenic immunosuppression.
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影响因子：
17.1
作者：
Bharat A;Querrey M;Markov NS;Kim S;Kurihara C;Garza-Castillon R;Manerikar A;Shilatifard A;Tomic R;Politanska Y;Abdala-Valencia H;Yeldandi AV;Lomasney JW;Misharin AV;Budinger GRS
通讯作者：
Budinger GRS
影响因子：
158.5
作者：
Ackermann, Maximilian;Verleden, Stijn E.;Jonigk, Danny
通讯作者：
Jonigk, Danny
影响因子：
3.4
作者：
Guerini-Rocco, Elena;Taormina, Sergio Vincenzo;Barberis, Massimo
通讯作者：
Barberis, Massimo
影响因子：
3.5
作者：
Pernazza, Angelina;Mancini, Massimiliano;D'Amati, Giulia
通讯作者：
D'Amati, Giulia
DOI：
10.1001/jama.2020.6775
发表时间：
2020-01-01
期刊：
JAMA, Journal of the American Medical Association
影响因子：
--
作者：
Richardson, Safiya;Hirsch, Jamie S.;,
通讯作者：
,