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Article ; Online: Immunological signatures unveiled by integrative systems vaccinology characterization of dengue vaccination trials and natural infection.

Plaça, Desirée Rodrigues / Fonseca, Dennyson Leandro M / Marques, Alexandre H C / Zaki Pour, Shahab / Usuda, Júlia Nakanishi / Baiocchi, Gabriela Crispim / Prado, Caroline Aliane de Souza / Salgado, Ranieri Coelho / Filgueiras, Igor Salerno / Freire, Paula Paccielli / Rocha, Vanderson / Camara, Niels Olsen Saraiva / Catar, Rusan / Moll, Guido / Jurisica, Igor / Calich, Vera Lúcia Garcia / Giil, Lasse M / Rivino, Laura / Ochs, Hans D /

Cabral-Miranda, Gustavo / Schimke, Lena F / Cabral-Marques, Otavio

Frontiers in immunology

2024 Volume 15, Page(s) 1282754

Abstract: Introduction: Dengue virus infection is a global health problem lacking specific therapy, requiring an improved understanding of DENV immunity and vaccine responses. Considering the recent emerging of new dengue vaccines, here we performed an ... ...

Abstract	Introduction: Dengue virus infection is a global health problem lacking specific therapy, requiring an improved understanding of DENV immunity and vaccine responses. Considering the recent emerging of new dengue vaccines, here we performed an integrative systems vaccinology characterization of molecular signatures triggered by the natural DENV infection (NDI) and attenuated dengue virus infection models (DVTs). Methods and results: We analyzed 955 samples of transcriptomic datasets of patients with NDI and attenuated dengue virus infection trials (DVT1, DVT2, and DVT3) using a systems vaccinology approach. Differential expression analysis identified 237 common differentially expressed genes (DEGs) between DVTs and NDI. Among them, 28 and 60 DEGs were up or downregulated by dengue vaccination during DVT2 and DVT3, respectively, with 20 DEGs intersecting across all three DVTs. Enriched biological processes of these genes included type I/II interferon signaling, cytokine regulation, apoptosis, and T-cell differentiation. Principal component analysis based on 20 common DEGs (overlapping between DVTs and our NDI validation dataset) distinguished dengue patients by disease severity, particularly in the late acute phase. Machine learning analysis ranked the ten most critical predictors of disease severity in NDI, crucial for the anti-viral immune response. Conclusion: This work provides insights into the NDI and vaccine-induced overlapping immune response and suggests molecular markers (e.g.,
MeSH term(s)	Humans ; Vaccinology ; Vaccines ; Virus Diseases ; Vaccination ; Dengue/prevention & control
Chemical Substances	Vaccines
Language	English
Publishing date	2024-02-20
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2024.1282754
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Article ; Online: Severe COVID-19 patients exhibit elevated levels of autoantibodies targeting cardiolipin and platelet glycoprotein with age: a systems biology approach.

Fonseca, Dennyson Leandro M / Filgueiras, Igor Salerno / Marques, Alexandre H C / Vojdani, Elroy / Halpert, Gilad / Ostrinski, Yuri / Baiocchi, Gabriela Crispim / Plaça, Desirée Rodrigues / Freire, Paula P / Pour, Shahab Zaki / Moll, Guido / Catar, Rusan / Lavi, Yael Bublil / Silverberg, Jonathan I / Zimmerman, Jason / Cabral-Miranda, Gustavo / Carvalho, Robson F / Khan, Taj Ali / Heidecke, Harald /

Dalmolin, Rodrigo J S / Luchessi, Andre Ducati / Ochs, Hans D / Schimke, Lena F / Amital, Howard / Riemekasten, Gabriela / Zyskind, Israel / Rosenberg, Avi Z / Vojdani, Aristo / Shoenfeld, Yehuda / Cabral-Marques, Otavio

npj aging

2023 Volume 9, Issue 1, Page(s) 21

Abstract: Age is a significant risk factor for the coronavirus disease 2019 (COVID-19) severity due to immunosenescence and certain age-dependent medical conditions (e.g., obesity, cardiovascular disorder, and chronic respiratory disease). However, despite the ... ...

Abstract	Age is a significant risk factor for the coronavirus disease 2019 (COVID-19) severity due to immunosenescence and certain age-dependent medical conditions (e.g., obesity, cardiovascular disorder, and chronic respiratory disease). However, despite the well-known influence of age on autoantibody biology in health and disease, its impact on the risk of developing severe COVID-19 remains poorly explored. Here, we performed a cross-sectional study of autoantibodies directed against 58 targets associated with autoimmune diseases in 159 individuals with different COVID-19 severity (71 mild, 61 moderate, and 27 with severe symptoms) and 73 healthy controls. We found that the natural production of autoantibodies increases with age and is exacerbated by SARS-CoV-2 infection, mostly in severe COVID-19 patients. Multiple linear regression analysis showed that severe COVID-19 patients have a significant age-associated increase of autoantibody levels against 16 targets (e.g., amyloid β peptide, β catenin, cardiolipin, claudin, enteric nerve, fibulin, insulin receptor a, and platelet glycoprotein). Principal component analysis with spectrum decomposition and hierarchical clustering analysis based on these autoantibodies indicated an age-dependent stratification of severe COVID-19 patients. Random forest analysis ranked autoantibodies targeting cardiolipin, claudin, and platelet glycoprotein as the three most crucial autoantibodies for the stratification of severe COVID-19 patients ≥50 years of age. Follow-up analysis using binomial logistic regression found that anti-cardiolipin and anti-platelet glycoprotein autoantibodies significantly increased the likelihood of developing a severe COVID-19 phenotype with aging. These findings provide key insights to explain why aging increases the chance of developing more severe COVID-19 phenotypes.
Language	English
Publishing date	2023-08-24
Publishing country	England
Document type	Journal Article
ISSN	2731-6068
ISSN (online)	2731-6068
DOI	10.1038/s41514-023-00118-0
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Article ; Online: Integrative systems immunology uncovers molecular networks of the cell cycle that stratify COVID-19 severity.

Prado, Caroline Aliane de Souza / Fonseca, Dennyson Leandro M / Singh, Youvika / Filgueiras, Igor Salerno / Baiocchi, Gabriela Crispim / Plaça, Desirée Rodrigues / Marques, Alexandre H C / Dantas-Komatsu, Raquel Costa Silva / Usuda, Júlia N / Freire, Paula Paccielli / Salgado, Ranieri Coelho / Napoleao, Sarah Maria da Silva / Ramos, Rodrigo Nalio / Rocha, Vanderson / Zhou, Guangyan / Catar, Rusan / Moll, Guido / Camara, Niels Olsen Saraiva / de Miranda, Gustavo Cabral /

Calich, Vera Lúcia Garcia / Giil, Lasse M / Mishra, Neha / Tran, Florian / Luchessi, Andre Ducati / Nakaya, Helder I / Ochs, Hans D / Jurisica, Igor / Schimke, Lena F / Cabral-Marques, Otavio

Journal of medical virology

2023 Volume 95, Issue 2, Page(s) e28450

Abstract: Several perturbations in the number of peripheral blood leukocytes, such as neutrophilia and lymphopenia associated with Coronavirus disease 2019 (COVID-19) severity, point to systemic molecular cell cycle alterations during severe acute respiratory ... ...

Abstract	Several perturbations in the number of peripheral blood leukocytes, such as neutrophilia and lymphopenia associated with Coronavirus disease 2019 (COVID-19) severity, point to systemic molecular cell cycle alterations during severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. However, the landscape of cell cycle alterations in COVID-19 remains primarily unexplored. Here, we performed an integrative systems immunology analysis of publicly available proteome and transcriptome data to characterize global changes in the cell cycle signature of COVID-19 patients. We found significantly enriched cell cycle-associated gene co-expression modules and an interconnected network of cell cycle-associated differentially expressed proteins (DEPs) and genes (DEGs) by integrating the molecular data of 1469 individuals (981 SARS-CoV-2 infected patients and 488 controls [either healthy controls or individuals with other respiratory illnesses]). Among these DEPs and DEGs are several cyclins, cell division cycles, cyclin-dependent kinases, and mini-chromosome maintenance proteins. COVID-19 patients partially shared the expression pattern of some cell cycle-associated genes with other respiratory illnesses but exhibited some specific differential features. Notably, the cell cycle signature predominated in the patients' blood leukocytes (B, T, and natural killer cells) and was associated with COVID-19 severity and disease trajectories. These results provide a unique global understanding of distinct alterations in cell cycle-associated molecules in COVID-19 patients, suggesting new putative pathways for therapeutic intervention.
MeSH term(s)	Humans ; COVID-19 ; SARS-CoV-2 ; Transcriptome ; Killer Cells, Natural ; Cell Cycle
Language	English
Publishing date	2023-01-04
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	752392-0
ISSN	1096-9071 ; 0146-6615
ISSN (online)	1096-9071
ISSN	0146-6615
DOI	10.1002/jmv.28450
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Article ; Online: Severe COVID-19 Shares a Common Neutrophil Activation Signature with Other Acute Inflammatory States.

Schimke, Lena F / Marques, Alexandre H C / Baiocchi, Gabriela Crispim / de Souza Prado, Caroline Aliane / Fonseca, Dennyson Leandro M / Freire, Paula Paccielli / Rodrigues Plaça, Desirée / Salerno Filgueiras, Igor / Coelho Salgado, Ranieri / Jansen-Marques, Gabriel / Rocha Oliveira, Antonio Edson / Peron, Jean Pierre Schatzmann / Cabral-Miranda, Gustavo / Barbuto, José Alexandre Marzagão / Camara, Niels Olsen Saraiva / Calich, Vera Lúcia Garcia / Ochs, Hans D / Condino-Neto, Antonio / Overmyer, Katherine A /

Coon, Joshua J / Balnis, Joseph / Jaitovich, Ariel / Schulte-Schrepping, Jonas / Ulas, Thomas / Schultze, Joachim L / Nakaya, Helder I / Jurisica, Igor / Cabral-Marques, Otávio

Cells

2022 Volume 11, Issue 5

Abstract: Severe COVID-19 patients present a clinical and laboratory overlap with other hyperinflammatory conditions such as hemophagocytic lymphohistiocytosis (HLH). However, the underlying mechanisms of these conditions remain to be explored. Here, we ... ...

Abstract	Severe COVID-19 patients present a clinical and laboratory overlap with other hyperinflammatory conditions such as hemophagocytic lymphohistiocytosis (HLH). However, the underlying mechanisms of these conditions remain to be explored. Here, we investigated the transcriptome of 1596 individuals, including patients with COVID-19 in comparison to healthy controls, other acute inflammatory states (HLH, multisystem inflammatory syndrome in children [MIS-C], Kawasaki disease [KD]), and different respiratory infections (seasonal coronavirus, influenza, bacterial pneumonia). We observed that COVID-19 and HLH share immunological pathways (cytokine/chemokine signaling and neutrophil-mediated immune responses), including gene signatures that stratify COVID-19 patients admitted to the intensive care unit (ICU) and COVID-19_nonICU patients. Of note, among the common differentially expressed genes (DEG), there is a cluster of neutrophil-associated genes that reflects a generalized hyperinflammatory state since it is also dysregulated in patients with KD and bacterial pneumonia. These genes are dysregulated at the protein level across several COVID-19 studies and form an interconnected network with differentially expressed plasma proteins that point to neutrophil hyperactivation in COVID-19 patients admitted to the intensive care unit. scRNAseq analysis indicated that these genes are specifically upregulated across different leukocyte populations, including lymphocyte subsets and immature neutrophils. Artificial intelligence modeling confirmed the strong association of these genes with COVID-19 severity. Thus, our work indicates putative therapeutic pathways for intervention.
MeSH term(s)	Artificial Intelligence ; COVID-19/complications ; COVID-19/genetics ; Child ; Humans ; Lymphohistiocytosis, Hemophagocytic/complications ; Neutrophil Activation ; SARS-CoV-2 ; Systemic Inflammatory Response Syndrome
Language	English
Publishing date	2022-03-01
Publishing country	Switzerland
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells11050847
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Article ; Online: Dysregulated autoantibodies targeting vaso- and immunoregulatory receptors in Post COVID Syndrome correlate with symptom severity.

Sotzny, Franziska / Filgueiras, Igor Salerno / Kedor, Claudia / Freitag, Helma / Wittke, Kirsten / Bauer, Sandra / Sepúlveda, Nuno / Mathias da Fonseca, Dennyson Leandro / Baiocchi, Gabriela Crispim / Marques, Alexandre H C / Kim, Myungjin / Lange, Tanja / Plaça, Desirée Rodrigues / Luebber, Finn / Paulus, Frieder M / De Vito, Roberta / Jurisica, Igor / Schulze-Forster, Kai / Paul, Friedemann /

Bellmann-Strobl, Judith / Rust, Rebekka / Hoppmann, Uta / Shoenfeld, Yehuda / Riemekasten, Gabriela / Heidecke, Harald / Cabral-Marques, Otavio / Scheibenbogen, Carmen

Frontiers in immunology

2022 Volume 13, Page(s) 981532

Abstract: Most patients with Post COVID Syndrome (PCS) present with a plethora of symptoms without clear evidence of organ dysfunction. A subset of them fulfills diagnostic criteria of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Symptom severity ... ...

Abstract	Most patients with Post COVID Syndrome (PCS) present with a plethora of symptoms without clear evidence of organ dysfunction. A subset of them fulfills diagnostic criteria of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Symptom severity of ME/CFS correlates with natural regulatory autoantibody (AAB) levels targeting several G-protein coupled receptors (GPCR). In this exploratory study, we analyzed serum AAB levels against vaso- and immunoregulatory receptors, mostly GPCRs, in 80 PCS patients following mild-to-moderate COVID-19, with 40 of them fulfilling diagnostic criteria of ME/CFS. Healthy seronegative (n=38) and asymptomatic post COVID-19 controls (n=40) were also included in the study as control groups. We found lower levels for various AABs in PCS compared to at least one control group, accompanied by alterations in the correlations among AABs. Classification using random forest indicated AABs targeting ADRB2, STAB1, and ADRA2A as the strongest classifiers (AABs stratifying patients according to disease outcomes) of post COVID-19 outcomes. Several AABs correlated with symptom severity in PCS groups. Remarkably, severity of fatigue and vasomotor symptoms were associated with ADRB2 AAB levels in PCS/ME/CFS patients. Our study identified dysregulation of AAB against various receptors involved in the autonomous nervous system (ANS), vaso-, and immunoregulation and their correlation with symptom severity, pointing to their role in the pathogenesis of PCS.
MeSH term(s)	Autoantibodies ; COVID-19 ; Fatigue Syndrome, Chronic ; Humans
Chemical Substances	Autoantibodies
Language	English
Publishing date	2022-09-27
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2022.981532
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Article: Corrigendum to "Cross-sectional analysis of students and school workers reveals a high number of asymptomatic SARS-CoV-2 infections during school reopening in Brazilian cities" [Heliyon 8 (11) (November 2022) Article e11368].

Borges, Lysandro P / Guimarães, Adriana G / Fonseca, Dennyson Leandro M / Freire, Paula P / Barreto, Íkaro D C / Souza, Daniela R V / Gurgel, Ricardo Q / Lopes, Aline S A / Melquiades de Rezende Neto, José / Dos Santos, Kezia A / Matos, Igor L S / da Invenção, Grazielly B / Oliveira, Brenda M / Santos, Aryanne A / Soares, Daniele Almeida / de Jesus, Pamela C / Dos Santos, Cliomar A / Goes, Marco A O / Plaça, Desirée Rodrigues /

Filgueiras, Igor Salerno / Marques, Alexandre H C / Baiocchi, Gabriela Crispim / CabralMiranda, William / Cabral de Miranda, Gustavo / Saraiva Camara, Niels Olsen / Garcia Calich, Vera Lúcia / Ramos, Rodrigo Nalio / Nakaya, Helder I / Rocha, Vanderson / Giil, Lasse M / Ochs, Hans D / Schimke, Lena F / de Souza, Mércia S F / Cuevas, Luis E / Martins, Aline F / Cabral-Marques, Otavio

Heliyon

2023 Volume 9, Issue 3, Page(s) e14398

Abstract: This corrects the article DOI: 10.1016/j.heliyon.2022.e11368.]. ...

Abstract	[This corrects the article DOI: 10.1016/j.heliyon.2022.e11368.].
Language	English
Publishing date	2023-03-15
Publishing country	England
Document type	Published Erratum
ZDB-ID	2835763-2
ISSN	2405-8440
ISSN	2405-8440
DOI	10.1016/j.heliyon.2023.e14398
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Article ; Online: Age-dependent impairment in antibody responses elicited by a homologous CoronaVac booster dose.

Filardi, Bruno Andraus / Monteiro, Valter Silva / Schwartzmann, Pedro Vellosa / do Prado Martins, Vivian / Zucca, Luis Eduardo Rosa / Baiocchi, Gabriela Crispim / Malik, Amyn A / Silva, Julio / Hahn, Anne M / Chen, Nicholas F G / Pham, Kien / Pérez-Then, Eddy / Miric, Marija / Brache, Vivian / Cochon, Leila / Larocca, Rafael A / Mendez, Roberto Della Rosa / Bardini Silveira, Douglas / Pinto, Aguinaldo Roberto /

Science translational medicine

2023 Volume 15, Issue 683, Page(s) eade6023

Abstract: The emergence of the SARS-CoV-2 Omicron sublineages resulted in increased transmission rates and reduced protection from vaccines. To counteract these effects, multiple booster strategies were used in different countries, although data comparing their ... ...

Abstract	The emergence of the SARS-CoV-2 Omicron sublineages resulted in increased transmission rates and reduced protection from vaccines. To counteract these effects, multiple booster strategies were used in different countries, although data comparing their efficiency in improving protective immunity remain sparse, especially among vulnerable populations, including older adults. The inactivated CoronaVac vaccine was among the most widely distributed vaccine worldwide and was essential in the early control of SARS-CoV-2-related hospitalizations and deaths. However, it is not well understood whether homologous versus heterologous booster doses in those fully vaccinated with CoronaVac induce distinct humoral responses or whether these responses vary across age groups. We analyzed plasma antibody responses from CoronaVac-vaccinated younger or older individuals who received a homologous CoronaVac or heterologous BNT162b2 or ChAdOx1 booster vaccine. All three evaluated boosters resulted in increased virus-specific IgG titers 28 days after the booster dose. However, we found that both IgG titers against SARS-CoV-2 Spike or RBD and neutralization titers against Omicron sublineages were substantially reduced in participants who received homologous CoronaVac compared with the heterologous BNT162b2 or ChAdOx1 booster. This effect was specifically prominent in recipients >50 years of age. In this group, the CoronaVac booster induced low virus-specific IgG titers and failed to elevate neutralization titers against any Omicron sublineage. Our results point to the notable inefficiency of CoronaVac immunization and boosting in mounting protective antiviral humoral immunity, particularly among older adults, during the Omicron wave. These observations also point to benefits of heterologous regimens in high-risk populations fully vaccinated with CoronaVac.
MeSH term(s)	Humans ; Aged ; Antibody Formation ; BNT162 Vaccine ; COVID-19 ; SARS-CoV-2 ; Immunoglobulin G ; Antibodies, Viral
Chemical Substances	sinovac COVID-19 vaccine ; BNT162 Vaccine ; Immunoglobulin G ; Antibodies, Viral
Language	English
Publishing date	2023-02-15
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, P.H.S.
ZDB-ID	2518854-9
ISSN	1946-6242 ; 1946-6234
ISSN (online)	1946-6242
ISSN	1946-6234
DOI	10.1126/scitranslmed.ade6023
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Article ; Online: Autoantibodies targeting G protein-coupled receptors: An evolving history in autoimmunity. Report of the 4th international symposium.

Cabral-Marques, Otávio / Moll, Guido / Catar, Rusan / Preuß, Beate / Bankamp, Lukas / Pecher, Ann-Christin / Henes, Joerg / Klein, Reinhild / Kamalanathan, A S / Akbarzadeh, Reza / van Oostveen, Wieke / Hohberger, Bettina / Endres, Matthias / Koolmoes, Bryan / Levarht, Nivine / Postma, Rudmer / van Duinen, Vincent / van Zonneveld, Anton Jan / de Vries-Bouwstra, Jeska /

Fehres, Cynthia / Tran, Florian / do Vale, Fernando Yuri Nery / da Silva Souza, Kamilla Batista / Filgueiras, Igor Salerno / Schimke, Lena F / Baiocchi, Gabriela Crispim / de Miranda, Gustavo Cabral / da Fonseca, Dennyson Leandro Mathias / Freire, Paula Paccielli / Hackel, Alexander M / Grasshoff, Hanna / Stähle, Anja / Müller, Antje / Dechend, Ralf / Yu, Xinhua / Petersen, Frank / Sotzny, Franziska / Sakmar, Thomas P / Ochs, Hans D / Schulze-Forster, Kai / Heidecke, Harald / Scheibenbogen, Carmen / Shoenfeld, Yehuda / Riemekasten, Gabriela

Autoimmunity reviews

2023 Volume 22, Issue 5, Page(s) 103310

Abstract: G protein-coupled receptors (GPCR) are involved in various physiological and pathophysiological processes. Functional autoantibodies targeting GPCRs have been associated with multiple disease manifestations in this context. Here we summarize and discuss ... ...

Abstract	G protein-coupled receptors (GPCR) are involved in various physiological and pathophysiological processes. Functional autoantibodies targeting GPCRs have been associated with multiple disease manifestations in this context. Here we summarize and discuss the relevant findings and concepts presented in the biennial International Meeting on autoantibodies targeting GPCRs (the 4th Symposium), held in Lübeck, Germany, 15-16 September 2022. The symposium focused on the current knowledge of these autoantibodies' role in various diseases, such as cardiovascular, renal, infectious (COVID-19), and autoimmune diseases (e.g., systemic sclerosis and systemic lupus erythematosus). Beyond their association with disease phenotypes, intense research related to the mechanistic action of these autoantibodies on immune regulation and pathogenesis has been developed, underscoring the role of autoantibodies targeting GPCRs on disease outcomes and etiopathogenesis. The observation repeatedly highlighted that autoantibodies targeting GPCRs could also be present in healthy individuals, suggesting that anti-GPCR autoantibodies play a physiologic role in modeling the course of diseases. Since numerous therapies targeting GPCRs have been developed, including small molecules and monoclonal antibodies designed for treating cancer, infections, metabolic disorders, or inflammatory conditions, anti-GPCR autoantibodies themselves can serve as therapeutic targets to reduce patients' morbidity and mortality, representing a new area for the development of novel therapeutic interventions.
MeSH term(s)	Humans ; Autoantibodies ; Autoimmunity ; COVID-19 ; Autoimmune Diseases ; Receptors, G-Protein-Coupled/metabolism
Chemical Substances	Autoantibodies ; Receptors, G-Protein-Coupled
Language	English
Publishing date	2023-03-10
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	2144145-5
ISSN	1873-0183 ; 1568-9972
ISSN (online)	1873-0183
ISSN	1568-9972
DOI	10.1016/j.autrev.2023.103310
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Article ; Online: The network interplay of interferon and Toll-like receptor signaling pathways in the anti-Candida immune response.

Salgado, Ranieri Coelho / Fonseca, Dennyson Leandro M / Marques, Alexandre H C / da Silva Napoleao, Sarah Maria / França, Tábata Takahashi / Akashi, Karen Tiemi / de Souza Prado, Caroline Aliane / Baiocchi, Gabriela Crispim / Plaça, Desirée Rodrigues / Jansen-Marques, Gabriel / Filgueiras, Igor Salerno / De Vito, Roberta / Freire, Paula Paccielli / de Miranda, Gustavo Cabral / Camara, Niels Olsen Saraiva / Calich, Vera Lúcia Garcia / Ochs, Hans D / Schimke, Lena F / Jurisica, Igor /

Condino-Neto, Antonio / Cabral-Marques, Otavio

Scientific reports

2021 Volume 11, Issue 1, Page(s) 20281

Abstract: Fungal infections represent a major global health problem affecting over a billion people that kills more than 1.5 million annually. In this study, we employed an integrative approach to reveal the landscape of the human immune responses to Candida spp. ... ...

Abstract	Fungal infections represent a major global health problem affecting over a billion people that kills more than 1.5 million annually. In this study, we employed an integrative approach to reveal the landscape of the human immune responses to Candida spp. through meta-analysis of microarray, bulk, and single-cell RNA sequencing (scRNA-seq) data for the blood transcriptome. We identified across these different studies a consistent interconnected network interplay of signaling molecules involved in both Toll-like receptor (TLR) and interferon (IFN) signaling cascades that is activated in response to different Candida species (C. albicans, C. auris, C. glabrata, C. parapsilosis, and C. tropicalis). Among these molecules are several types I IFN, indicating an overlap with antiviral immune responses. scRNA-seq data confirmed that genes commonly identified by the three transcriptomic methods show cell type-specific expression patterns in various innate and adaptive immune cells. These findings shed new light on the anti-Candida immune response, providing putative molecular pathways for therapeutic intervention.
MeSH term(s)	Antiviral Agents/pharmacology ; Candida albicans/immunology ; Candida glabrata/immunology ; Candida parapsilosis/immunology ; Candidiasis/immunology ; Candidiasis/microbiology ; Computational Biology/methods ; Databases, Genetic ; Gene Expression Profiling ; Gene Expression Regulation, Fungal ; Humans ; Immunity ; Immunity, Innate ; Interferons/metabolism ; RNA-Seq ; Signal Transduction/immunology ; Transcription, Genetic ; Transcriptome
Chemical Substances	Antiviral Agents ; Interferons (9008-11-1)
Language	English
Publishing date	2021-10-13
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-021-99838-0
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Article ; Online: Autoantibodies linked to autoimmune diseases associate with COVID-19 outcomes

Baiocchi, Gabriela Crispim / Vojdani, Aristo / Rosenberg, Avi Z / Vojdani, Elroy / Halpert, Gilad / Ostrinski, Yuri / Zyskind, Israel / Filgueiras, Igor Salerno / Schimke, Lena F. / Marques, Alexandre H. C. / Giil, Lasse M. / Lavi, Yael Bublil / Silverberg, Jonathan I. / Zimmerman, Jason / Hill, Dana Ashley / Thornton, Amanda / Kim, Myungjin / De Vito, Roberta / Fonseca, Dennyson Leandro M. /

Placa, Desiree Rodrigues / Freire, Paula Paccielli / Camara, Niels Olsen Saraiva / Calich, Vera Lucia Garcia / Heidecke, Harald / Lattin, Miriam T. / Ochs, Hans D. / Riemekasten, Gabriela / Amital, Howard / Marques, Otavio Cabral / Shoenfeld, Yehuda

medRxiv

Abstract: The SARS-CoV-2 infection is associated with increased levels of autoantibodies targeting immunological proteins such as cytokines and chemokines. Reports further indicate that COVID-19 patients may develop a wide spectrum of autoimmune diseases due to ... ...

Abstract	The SARS-CoV-2 infection is associated with increased levels of autoantibodies targeting immunological proteins such as cytokines and chemokines. Reports further indicate that COVID-19 patients may develop a wide spectrum of autoimmune diseases due to reasons not fully understood. Even so, the landscape of autoantibodies induced by SARS-CoV-2 infection remains uncharted territory. To gain more insight, we carried out a comprehensive assessment of autoantibodies known to be linked to diverse autoimmune diseases observed in COVID-19 patients, in a cohort of 248 individuals, of which 171 were COVID-19 patients (74 with mild, 65 moderate, and 32 with severe disease) and 77 were healthy controls. Dysregulated autoantibody serum levels, characterized mainly by elevated concentrations, occurred mostly in patients with moderate or severe COVID-19 infection, and was accompanied by a progressive disruption of physiologic IgG and IgA autoantibody signatures. A similar perturbation was found in patients with anosmia. Notably, autoantibody levels often accompanied anti-SARS-CoV-2 antibody concentrations, being both indicated by random forest classification as strong predictors of COVID-19 outcome, together with age. Moreover, higher levels of autoantibodies (mainly IgGs) were seen in the elderly with severe disease compared with young COVID-19 patients with severe disease. These findings suggest that the SARS-CoV-2 infection induces a broader loss of self-tolerance than previously thought, providing new ideas for therapeutic interventions.
Keywords	covid19
Language	English
Publishing date	2022-02-18
Publisher	Cold Spring Harbor Laboratory Press
Document type	Article ; Online
DOI	10.1101/2022.02.17.22271057
Database	COVID19

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