Complement as a vital nexus of the pathobiological connectome for acute respiratory distress syndrome: An emerging therapeutic target DOI Creative Commons
Zhangsheng Yang, Susannah E. Nicholson,

Tomas S. Cancio

et al.

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: March 17, 2023

The hallmark of acute respiratory distress syndrome (ARDS) pathobiology is unchecked inflammation-driven diffuse alveolar damage and alveolar-capillary barrier dysfunction. Currently, therapeutic interventions for ARDS remain largely limited to pulmonary-supportive strategies, there an unmet demand pharmacologic therapies targeting the underlying pathology in patients suffering from illness. complement cascade (ComC) plays integral role regulation both innate adaptive immune responses. ComC activation can prime overzealous cytokine storm tissue/organ damage. lung injury (ALI) have established relationship with early maladaptive activation. In this review, we collected evidence current studies linking ALI/ARDS dysregulation, focusing on elucidating new emerging roles extracellular (canonical) intracellular (non-canonical or complosome), (complementome) pathobiology, highlighting complementome as a vital nexus pathobiological connectome via its crosstalking other systems immunome, DAMPome, PAMPome, coagulome, metabolome, microbiome. We also discussed diagnostic/therapeutic potential future direction care ultimate goal better defining mechanistic subtypes (endotypes theratypes) through methodologies order facilitate more precise effective complement-targeted therapy treating these comorbidities. This information leads support anti-inflammatory strategy by ComC, where arsenal clinical-stage complement-specific drugs available, especially due COVID-19.

Language: Английский

Atypical hemolytic uremic syndrome with a C3 variant following COVID-19: a case report DOI Creative Commons
Masato Ando, Kazuo Kubota,

Saori Kadowaki

et al.

Frontiers in Pediatrics, Journal Year: 2025, Volume and Issue: 13

Published: Jan. 23, 2025

Atypical hemolytic uremic syndrome (aHUS) is a form of thrombotic microangiopathy (TMA) characterized by the triad microangiopathic anemia, thrombocytopenia, and acute kidney injury, caused overactivation alternative complement pathway. A 13-year-old Japanese boy with an unremarkable medical history developed symptoms TMA following coronavirus disease 2019 (COVID-19) infection mild respiratory symptoms. He was eventually diagnosed aHUS gain-of-function C3 variant. improved supportive therapy plasma exchange, did not require anti-C5 antibody therapy. In literature, more than 20 cases de novo or relapsed have been described COVID-19. It has shown that lectin pathway can be activated severe 2 (SARS-CoV-2) spike N proteins, SARS-CoV-2 protein. The current case highlights possibility COVID-19, even when are severe, trigger aHUS.

Language: Английский

Citations

1
Preeclamptic Placental CD19+ B Cells Are Causal to Hypertension During Pregnancy DOI
Owen Herrock, Nathan Campbell, Evangeline Deer

et al.

Hypertension, Journal Year: 2025, Volume and Issue: unknown

Published: April 2, 2025

BACKGROUND: Patients with preeclampsia exhibit hypertension and chronic inflammation characterized by CD (cluster determinant) 4+T cells, B cells secreting AT1-AA (agonistic autoantibody against the angiotensin II type 1 receptor), inflammatory cytokines, complement activation. Importantly, a history of COVID-19 during pregnancy is associated an increased incidence preeclampsia-like phenotype partly mediated CD4+T cells. We recently showed pregnant patients or without produce AT1-AA, indicating importance lymphocytes in progression possibly COVID-19. Therefore, we hypothesize that from induce through AT1-AA. METHODS: Placental were isolated normal pregnant, preeclampsia, normotensive history, at delivery. Then, 3×10 5 transferred intraperitoneally into athymic rats gestational day 12. On 18, carotid catheters inserted. 19, mean arterial pressure was measured, tissues collected. RESULTS: Preeclampsia B-cell recipients had significantly pressure, activation compared recipients. Recipients markers but not to level significance as Inhibition attenuated occurred response history. CONCLUSIONS: This study demonstrates important role contributing secretion

Language: Английский

Citations

1
Hyperinflammation and Immune Response Generation in COVID-19 DOI Creative Commons
K.P. Mishra, Ajay Singh, Shashi Bala Singh

et al.

NeuroImmunoModulation, Journal Year: 2020, Volume and Issue: 27(2), P. 80 - 86

Published: Jan. 1, 2020

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) that causes coronavirus disease 2019 (COVID-19) pandemic has affected millions of people worldwide. The pathophysiology this virus is not very clearly known, thus, enormous efforts are being made by the scientific community to delineate its evading mechanism. In review, we have summarized hyperinflammation and humoral cell-mediated immune response generated in human body after infection with SARS-CoV-2 virus. inflammatory increased proinflammatory cytokines chemokines, complement proteins activation may likely contribute severity. We also discussed other factors affect immunity could be important comorbidities severity outcome.

Language: Английский

Citations

51
Complement Mediated Hemolytic Anemias in the COVID-19 Era: Case Series and Review of the Literature DOI Creative Commons
Bruno Fattizzo, Raffaella Pasquale,

Valentina Bellani

et al.

Frontiers in Immunology, Journal Year: 2021, Volume and Issue: 12

Published: Nov. 25, 2021

The complex pathophysiologic interplay between SARS-CoV-2 infection and complement activation is the subject of active investigation. It clinically mirrored by occurrence exacerbations mediated diseases during COVID-19 infection. These include complement-mediated hemolytic anemias such as paroxysmal nocturnal hemoglobinuria (PNH), autoimmune anemia (AIHA), particularly cold agglutinin disease (CAD), uremic syndrome (HUS). All these conditions may benefit from inhibitors that are also under study for disease. Hemolytic in occur upon several triggers including infections vaccines require transfusions, treatment with and/or immunosuppressors (i.e., steroids rituximab AIHA), result thrombotic complications. In this manuscript we describe four patients (2 PNH 2 CAD) who experienced flares after either or SARS-Cov2 vaccine provide a review most recent literature. We report episodes occurred within first 10 days infection/vaccination suggest laboratory monitoring (Hb LDH levels) period. Moreover, our experience literature, occurring were more severe, required greater therapeutic intervention, carried complications fatalities, compared to those developing vaccine, suggesting importance vaccinating patient population. Patient education remains pivotal promptly recognize signs/symptoms refer medical attention. Treatment choice should be based on severity exacerbation well Therapies inhibitor initiation/additional dose case PNH, steroids/rituximab CAD warm type AIHA, plasma exchange, hemodialysis atypical HUS. Finally, anti-thrombotic prophylaxis always considered settings, provided safe platelet counts.

Language: Английский

Citations

42
The role of SARS-CoV-2 nucleocapsid protein in antiviral immunity and vaccine development DOI Creative Commons
Haiyun Yu, Fei Guan,

Heather Miller

et al.

Emerging Microbes & Infections, Journal Year: 2022, Volume and Issue: 12(1)

Published: Dec. 30, 2022

ABSTRACTThe coronavirus disease 2019 (COVID-19) has caused enormous health risks and global economic disruption. This is by the severe acute respiratory syndrome 2 (SARS-CoV-2). The SARS-CoV-2 nucleocapsid protein a structural involved in viral replication assembly. There accumulating evidence indicating that multi-functional, playing key role pathogenesis of COVID-19 antiviral immunity against SARS-CoV-2. Here, we summarize its potential application prevention COVID-19, which based on inflammation, cell death, innate immunity, adaptive immunity.

Language: Английский

Citations

29
SARS-CoV-2 Related Antibody-Dependent Enhancement Phenomena In Vitro and In Vivo DOI Creative Commons

Emi E. Nakayama,

Tatsuo Shioda

Microorganisms, Journal Year: 2023, Volume and Issue: 11(4), P. 1015 - 1015

Published: April 13, 2023

Antibody-dependent enhancement (ADE) is a phenomenon in which antibodies produced the body after infection or vaccination may enhance subsequent viral infections vitro and vivo. Although rare, symptoms of diseases are also enhanced by ADE following This thought to be due production with low neutralizing activity that bind virus facilitate entry, antigen-antibody complexes cause airway inflammation, predominance T-helper 2 cells among immune system leads excessive eosinophilic tissue infiltration. Notably, disease different phenomena overlap. In this article, we will describe three types ADE: (1) Fc receptor (FcR)-dependent macrophages, (2) FcR-independent other cells, (3) FcR-dependent cytokine macrophages. We their relationship natural infection, discuss possible involvement COVID-19 pathogenesis.

Language: Английский

Citations

22
Emerging role of complement in COVID-19 and other respiratory virus diseases DOI Creative Commons
Mark Xiao, Calder Ellsworth, Xuebin Qin

et al.

Cellular and Molecular Life Sciences, Journal Year: 2024, Volume and Issue: 81(1)

Published: Feb. 18, 2024

Abstract The complement system, a key component of innate immunity, provides the first line defense against bacterial infection; however, COVID-19 pandemic has revealed that it may also engender severe complications in context viral respiratory disease. Here, we review mechanisms activation and regulation explore their roles both protecting infection exacerbating We discuss emerging evidence related to complement-targeted therapeutics compare role other diseases like influenza syncytial virus. recent mechanistic studies animal models can be used for further investigation. Novel knockout are proposed better understand nuances system diseases.

Language: Английский

Citations

8
The Key to Increase Immunogenicity of Next-Generation COVID-19 Vaccines Lies in the Inclusion of the SARS-CoV-2 Nucleocapsid Protein DOI Creative Commons
Noe Juvenal Mendoza-Ramírez, Julio García‐Cordero, Gaurav Shrivastava

et al.

Journal of Immunology Research, Journal Year: 2024, Volume and Issue: 2024, P. 1 - 18

Published: May 29, 2024

Vaccination is one of the most effective prophylactic public health interventions for prevention infectious diseases such as coronavirus disease (COVID-19). Considering ongoing need new COVID-19 vaccines, it crucial to modify our approach and incorporate more conserved regions severe acute respiratory syndrome 2 (SARS-CoV-2) effectively address emerging viral variants. The nucleocapsid protein a structural SARS-CoV-2 that involved in replication immune responses. Furthermore, this offers significant advantages owing minimal accumulation mutations over time inclusion key T-cell epitopes critical immunity. A novel strategy may be suitable generation vaccines against use combination antigens, including spike proteins, elicit robust humoral potent cellular responses, along with long-lasting strategic multiple antigens aims enhance vaccine efficacy broaden protection viruses, their response from other long-lasting, can persist up 11 years post-infection. Thus, incorporation nucleocapsids (N) into design adds an important dimension vaccination efforts holds promise bolstering ability combat effectively. In review, we summarize preclinical studies evaluated antigen. This study discusses alone its or proteins SARS-CoV-2.

Language: Английский

Citations

6
Targeting intra-viral conserved nucleocapsid (N) proteins as novel vaccines against SARS-CoVs DOI Open Access
Min Thura, Joel Sng, Koon Hwee Ang

et al.

Bioscience Reports, Journal Year: 2021, Volume and Issue: 41(9)

Published: Sept. 1, 2021

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused the global pandemic of Coronavirus disease in late 2019 (COVID-19). Vaccine development efforts have predominantly been aimed at 'Extra-viral' Spike (S) protein as vaccine vehicles, but there are concerns regarding 'viral immune escape' since multiple mutations may enable mutated virus strains to escape from immunity against S protein. The 'Intra-viral' Nucleocapsid (N-protein) is relatively conserved among mutant coronaviruses during spread and evolution. Herein, we demonstrate novel candidates SARS-CoV-2 by using whole N-protein or its fragment/peptides. Using ELISA assay, showed that high titers specific anti-N antibodies (IgG, IgG1, IgG2a, IgM) were maintained for a reasonably long duration (> 5 months), suggesting an excellent immunogen stimulate host system robust B-cell activation. We synthesized three peptides located regions CoVs. One peptide good vaccination well. Cytokine arrays on post-vaccination mouse sera progressive up-regulation various cytokines such IFN-γ CCL5, TH1 associated responses also stimulated. Furthermore, vaccinated mice exhibited elevated memory T cells population. Here, propose unconventional strategy targeting alternative target coronaviruses. Moreover, generated monoclonal antibody specifically epitope shared between SARS-CoV SARS-CoV-2, currently developing First-in-Class humanized anti-N-protein potentially treat patients infected CoVs future.

Language: Английский

Citations

41
Severe COVID-19 is associated with hyperactivation of the alternative complement pathway DOI Creative Commons
Jérémy Boussier, Nader Yatim, A. Marchal

et al.

Journal of Allergy and Clinical Immunology, Journal Year: 2021, Volume and Issue: 149(2), P. 550 - 556.e2

Published: Nov. 17, 2021

Language: Английский

Citations

34