Potential Implications of a Type 1 Interferon Gene Signature on COVID-19 Severity and Chronic Inflammation in Sickle Cell Disease.
Potential Implications of a Type 1 Interferon Gene Signature on COVID-19 Severity and Chronic Inflammation in Sickle Cell Disease.
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DOI：
10.3389/fmed.2021.679030
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发表时间：
2021
影响因子：
3.9
通讯作者：
Gibb DR
中科院分区：
文献类型：
--
作者：
Madany E;Okwan-Duodu D;Balbuena-Merle R;Hendrickson JE;Gibb DR
在冠状病毒病19(新冠肺炎)大流行开始时，有人担心镰状细胞病患者可能特别容易受到SARS-CoV-2感染的严重后遗症的影响。虽然有两份报告支持这一结论，但多项研究报告了SCD患者出人意料的良好结果。然而，缺乏解释这些不同结论的机制。在这里，我们回顾最近的研究表明，大多数系统性红斑狼疮患者在他们的基线健康状态下，抗病毒1型干扰素(干扰素α/β)和干扰素刺激基因水平升高，与新冠肺炎无关。我们还提供了新冠肺炎时代之前的数据，说明与种族匹配的对照组相比，在一组SCD患者中，一个特征良好的干扰素刺激基因的表达上调。这些1型干扰素和干扰素刺激基因有可能导致新冠肺炎和其他病毒感染在SCD患者中的可变进展。虽然大多数证据支持保护作用，但干扰素α/β在普通人群新冠肺炎严重程度中的作用仍是当前研究的一个领域。我们得出结论，系统性红斑狼疮患者的1型干扰素反应可能是先前研究报告的可变新冠肺炎反应的原因之一。进一步研究干扰素α/β产生的机制和干扰素α/β介导的炎症在SCD疾病中的其他临床后果是有必要的。假设：基线的I型干扰素活性可能与SCD的新冠肺炎进展有关。(上)在SARS-CoV-2感染的早期阶段，高基线干扰素α/β活性可能有助于SCD患者的抗病毒反应。模式识别受体识别损伤相关的分子模式，诱导干扰素α/β的产生。溶血镰状细胞释放的血红素与Toll样受体4结合，可诱导血管内皮细胞产生干扰素α/β。干扰素α/β与中性粒细胞和其他类型细胞中的干扰素α/β受体(IFNAR)结合，导致MxA和其他干扰素刺激基因(ISGs)的产生。ISGS可直接抑制病毒复制，促进B细胞产生中和抗体。干扰素α/β反应是先天性和获得性免疫细胞产生的多种反应之一，包括产生IL-6、肿瘤坏死因子α和IL-1b，这些细胞有可能限制新冠肺炎的进展。(下图)相反，干扰素α/β活性降低或缺失可能会增加病毒感染的易感性，导致呼吸道上皮细胞死亡和新冠肺炎。虚线表示潜在的连接路径，而实线则得到先前研究的支持。
At the onset of the corona virus disease 19 (COVID-19) pandemic, there were concerns that patients with sickle cell disease (SCD) might be especially vulnerable to severe sequelae of SARS-CoV-2 infection. While two reports support this conclusion, multiple studies have reported unexpectedly favorable outcomes in patients with SCD. However, mechanisms explaining these disparate conclusions are lacking. Here, we review recent studies indicating that the majority of patients with SCD express elevated levels of anti-viral type 1 interferons (IFNα/β) and interferon stimulated genes, independent of COVID-19, during their baseline state of health. We also present our data from the pre-COVID-19 era, illustrating elevated expression of a well-characterized interferon stimulated gene in a cohort of patients with SCD, compared to race-matched controls. These type 1 interferons and interferon stimulated genes have the potential to contribute to the variable progression of COVID-19 and other viral infections in patients with SCD. While the majority of evidence supports a protective role, the role of IFNα/β in COVID-19 severity in the general population remains an area of current investigation. We conclude that type 1 interferon responses in patients with SCD may contribute to the variable COVID-19 responses reported in prior studies. Additional studies investigating the mechanisms underlying IFNα/β production and other clinical consequences of IFNα/β-mediated inflammation in SCD disease are warranted. Hypothesis: Baseline type I interferon activity may contribute to variable COVID-19 progression in SCD. (Top) At early stages of SARS-CoV-2 infection, high baseline IFNα/β activity may contribute to the anti-viral response in patients with SCD. Recognition of damage-associated molecular patterns by pattern recognition receptors (PRRs) induces IFNα/β production. Heme released from hemolyzed sickle cells binds Toll-like receptor 4 (TLR4), which may induce IFNα/β in vascular endothelial cells. IFNα/β bind to the IFNα/β receptor (IFNAR) in neutrophils and other cells types, leading to production of MxA and other interferon-stimulated genes (ISGs). ISGs can directly inhibit viral replication and promote B cell production of neutralizing antibodies. The IFNα/β response is one of multiple responses, including production of IL-6, TNFα, and IL-1b, by innate and adaptive immune cells that have the potential to limit COVID-19 progression. (Bottom) In contrast, reduced or absent IFNα/β activity may increase susceptibility to viral infection, leading to airway epithelial cell death and COVID-19. Dashed lines indicate potentially connected pathways, while solid lines are supported by prior studies.
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危及生命的Covid-19患者中针对I型IFN的自身抗体。
DOI：
10.1126/science.abd4585
发表时间：
2020-10-23
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Bastard P;Rosen LB;Zhang Q;Michailidis E;Hoffmann HH;Zhang Y;Dorgham K;Philippot Q;Rosain J;Béziat V;Manry J;Shaw E;Haljasmägi L;Peterson P;Lorenzo L;Bizien L;Trouillet-Assant S;Dobbs K;de Jesus AA;Belot A;Kallaste A;Catherinot E;Tandjaoui-Lambiotte Y;Le Pen J;Kerner G;Bigio B;Seeleuthner Y;Yang R;Bolze A;Spaan AN;Delmonte OM;Abers MS;Aiuti A;Casari G;Lampasona V;Piemonti L;Ciceri F;Bilguvar K;Lifton RP;Vasse M;Smadja DM;Migaud M;Hadjadj J;Terrier B;Duffy D;Quintana-Murci L;van de Beek D;Roussel L;Vinh DC;Tangye SG;Haerynck F;Dalmau D;Martinez-Picado J;Brodin P;Nussenzweig MC;Boisson-Dupuis S;Rodríguez-Gallego C;Vogt G;Mogensen TH;Oler AJ;Gu J;Burbelo PD;Cohen JI;Biondi A;Bettini LR;D'Angio M;Bonfanti P;Rossignol P;Mayaux J;Rieux-Laucat F;Husebye ES;Fusco F;Ursini MV;Imberti L;Sottini A;Paghera S;Quiros-Roldan E;Rossi C;Castagnoli R;Montagna D;Licari A;Marseglia GL;Duval X;Ghosn J;HGID Lab;NIAID-USUHS Immune Response to COVID Group;COVID Clinicians;COVID-STORM Clinicians;Imagine COVID Group;French COVID Cohort Study Group;Milieu Intérieur Consortium;CoV-Contact Cohort;Amsterdam UMC Covid-19 Biobank;COVID Human Genetic Effort;Tsang JS;Goldbach-Mansky R;Kisand K;Lionakis MS;Puel A;Zhang SY;Holland SM;Gorochov G;Jouanguy E;Rice CM;Cobat A;Notarangelo LD;Abel L;Su HC;Casanova JL
通讯作者：
Casanova JL
影响因子：
27.4
作者：
Grenn RC;Yalavarthi S;Gandhi AA;Kazzaz NM;Núñez-Álvarez C;Hernández-Ramírez D;Cabral AR;McCune WJ;Bockenstedt PL;Knight JS
通讯作者：
Knight JS
DOI：
10.1038/s41577-021-00522-1
发表时间：
2021-04
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
Carvalho T;Krammer F;Iwasaki A
通讯作者：
Iwasaki A
影响因子：
5.6
作者：
Baghaei P;Dastan F;Marjani M;Moniri A;Abtahian Z;Ghadimi S;Valizadeh M;Heshmatnia J;Sadat Mirenayat M;Abedini A;Kiani A;Eslaminejad A;MohammadReza Hashemian S;Jamaati H;Zali A;Akbar Velayati A;Tabarsi P
通讯作者：
Tabarsi P
DOI：
10.1084/jem.20021553
发表时间：
2003-03-17
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Bennett L;Palucka AK;Arce E;Cantrell V;Borvak J;Banchereau J;Pascual V
通讯作者：
Pascual V