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Buch ; Dissertation / Habilitation: S-Schichtproteine als molekulare Bausteine zur Funktionalisierung mikroelektronischer Sensorstrukturen

Blüher, Anja

2008

Verfasserangabe	von Anja Blüher
Sprache	Deutsch
Umfang	II, 129 S., Ill., graph. Darst.
Dokumenttyp	Buch ; Dissertation / Habilitation
Dissertation / Habilitation	Techn. Univ., Diss.--Dresden, 2008
Datenquelle	Katalog der Technische Informationsbibliothek Hannover

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Artikel ; Online: The Bacillus subtilis endospore crust: protein interaction network, architecture and glycosylation state of a potential glycoprotein layer.

Bartels, Julia / Blüher, Anja / López Castellanos, Sebastián / Richter, Marcus / Günther, Markus / Mascher, Thorsten

Molecular microbiology

2019 Band 112, Heft 5, Seite(n) 1576–1592

Abstract: The endospore of Bacillus subtilis is formed intracellularly upon nutrient starvation and is encased by proteinaceous shells. The outermost layer, the crust, is a postulated glycoprotein layer that is composed of six proteins: CotV, W, X, Y, Z and CgeA. ... ...

Abstract	The endospore of Bacillus subtilis is formed intracellularly upon nutrient starvation and is encased by proteinaceous shells. The outermost layer, the crust, is a postulated glycoprotein layer that is composed of six proteins: CotV, W, X, Y, Z and CgeA. Despite some insight into protein interactions and the identification of players in glycosylation, a clear picture of its architecture is still missing. Here, we report a comprehensive mutational analysis that confirms CotZ as the anchor of the crust, while the crust structure is provided by CotV, CotX and CotY. CotY seems to be the major structural component, while CotV and CotX are polar and co-depend on each other and partially on CotW. CotW is independent of other crust proteins, instead depending on outer coat proteins, indicating a role at the interface of crust and coat. CgeA is co-expressed with putative glycosyltransferases (CgeB and CgeD) and implicated in crust glycosylation. In accordance, we provide evidence that CgeB, CgeCDE, SpsA-L, SpsM and SpsNOPQR (formerly YfnHGFED) contribute to the glycosylation state of the spore. The crust polysaccharide layer consists of functionally linked rhamnose- and galactose-related variants and could contain rare sugars. It may therefore protect the crust against biological degradation and scavenging.
Mesh-Begriff(e)	Bacillus subtilis/genetics ; Bacillus subtilis/metabolism ; Bacterial Proteins/metabolism ; Glycosylation ; Glycosyltransferases/metabolism ; Membrane Glycoproteins/metabolism ; Nutrients/deficiency ; Protein Interaction Maps ; Spores, Bacterial/metabolism ; Spores, Bacterial/ultrastructure
Chemische Substanzen	Bacterial Proteins ; Membrane Glycoproteins ; spore-specific proteins, Bacillus ; Glycosyltransferases (EC 2.4.-)
Sprache	Englisch
Erscheinungsdatum	2019-09-19
Erscheinungsland	England
Dokumenttyp	Journal Article
ZDB-ID	619315-8
ISSN	1365-2958 ; 0950-382X
ISSN (online)	1365-2958
ISSN	0950-382X
DOI	10.1111/mmi.14381
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Buch ; Online: Metal ion binding and tolerance of bacteria cells in view of sensor applications

Jung, Jonas / Blüher, Anja / Lakatos, Mathias / Cuniberti, Gianaurelio

eISSN: 2194-878X

2018

Abstract: The biotechnological use of bacterial cells and cell components for the detection and accumulation of valuable substances, such as metals and rare earth elements in aqueous systems, is possible by utilizing innate binding characteristics of ... ...

Abstract	The biotechnological use of bacterial cells and cell components for the detection and accumulation of valuable substances, such as metals and rare earth elements in aqueous systems, is possible by utilizing innate binding characteristics of microorganisms. We have studied the bacteria cells of Lysinibacillus sphaericus JG-B53 and Sporosarcina ureae ATCC 13881 to assess their potential applicability for the detection of rare earth elements, base metals or precious metals in water. First, we have demonstrated the interactions of the cells with the metal complexes of Au, Ho and Y by studying the color changes of the respective solutions, scanning electron microscopy (SEM) imaging of the metal cluster decoration on the cell surfaces and cell growth tolerance tests. Based on these results, we have developed two potential sensor systems. A colorimetric sensor was established by applying gold nanoparticles (AuNPs) functionalized with surface-layer ( S -layer) proteins SslA of S. ureae ATCC 13881 or Slp1 of L. sphaericus JG-B53 for the selective detection of YCl 3 up to 1.67 × 10 −5 mol L −1 in water. Additionally, a regenerative sensor layer of S -layer proteins on a thin gold film was developed for the detection of 1 × 10 −4 mol L −1 YCl 3 in water by surface plasmon resonance (SPR) spectroscopy.
Thema/Rubrik (Code)	333
Sprache	Englisch
Erscheinungsdatum	2018-12-07
Erscheinungsland	de
Dokumenttyp	Buch ; Online
Datenquelle	BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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Artikel ; Online: Innovative Tumor Tissue Dissection Tool for Molecular Oncology Diagnostics.

Javey, Manana / Reinsch, Christina / Feldkamp, Mirjam / Siemann, Sandra / Blüher, Anja / Woestmann, Corinna / Cai, Lingling / Tran, Ian / May, Theresa / Havnar, Charles / Lo, Amy A / Hinzmann, Bernd / Heilek, Gabrielle / Palma, John F

The Journal of molecular diagnostics : JMD

2021 Band 23, Heft 4, Seite(n) 399–406

Abstract: Formalin-fixed, paraffin-embedded (FFPE) tissue is the most commonly used material for tumor molecular profiling, therapy selection, and prognostication. Tumor tissue enrichment by tissue dissection is highly recommended to generate quality data ... ...

Abstract	Formalin-fixed, paraffin-embedded (FFPE) tissue is the most commonly used material for tumor molecular profiling, therapy selection, and prognostication. Tumor tissue enrichment by tissue dissection is highly recommended to generate quality data reproducibly for use in downstream assays, such as real-time PCR and next-generation sequencing. The aim of this study was to evaluate the performance of the automated tissue dissection tool AVENIO Millisect System compared with a manual dissection method using 18 FFPE tissue specimens. The study assessed performance of these two methods with paraffinized and deparaffinized sections at 5- and 10-μm thickness as well as at low (5% to 10%) and high (>50%) tumor content. In addition, compatibility with various nucleic acid and protein extraction methods was assessed. Overall, dissection by Millisect resulted in statistically significantly higher yields of nucleic acids and protein compared with manual dissection (P = 0.00524). In downstream analysis on a statistically nonpowered sample set, EGFR mutation testing by PCR led to highly concordant results, and next-generation sequencing testing yielded significantly higher allelic frequencies when tissue was dissected by Millisect compared with manual scraping, demonstrating noninferiority of the automated method. In summary, the AVENIO Millisect System may replace manual labor and support automation of FFPE tumor tissue workflows in clinical molecular laboratories with high testing volumes with adequate validation.
Mesh-Begriff(e)	Carcinoma, Non-Small-Cell Lung/genetics ; Carcinoma, Non-Small-Cell Lung/pathology ; Colorectal Neoplasms/genetics ; Colorectal Neoplasms/pathology ; Data Accuracy ; Dissection/methods ; ErbB Receptors/genetics ; Fixatives/chemistry ; Formaldehyde/chemistry ; Gene Frequency ; High-Throughput Nucleotide Sequencing/methods ; Humans ; Lung ; Lung Neoplasms/genetics ; Lung Neoplasms/pathology ; Medical Oncology/methods ; Molecular Diagnostic Techniques/methods ; Mutation ; Neoplasms/diagnosis ; Paraffin Embedding/methods ; Polymerase Chain Reaction/methods ; Reproducibility of Results ; Tissue Fixation/methods
Chemische Substanzen	Fixatives ; Formaldehyde (1HG84L3525) ; EGFR protein, human (EC 2.7.10.1) ; ErbB Receptors (EC 2.7.10.1)
Sprache	Englisch
Erscheinungsdatum	2021-01-23
Erscheinungsland	United States
Dokumenttyp	Evaluation Study ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2000060-1
ISSN	1943-7811 ; 1525-1578
ISSN (online)	1943-7811
ISSN	1525-1578
DOI	10.1016/j.jmoldx.2021.01.006
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Highly multiplexed immune repertoire sequencing links multiple lymphocyte classes with severity of response to COVID-19.

Dannebaum, Richard / Suwalski, Phillip / Asgharian, Hosseinali / Du Zhipei, Gracie / Lin, Hai / Weiner, January / Holtgrewe, Manuel / Thibeault, Charlotte / Müller, Melina / Wang, Xiaomin / Karadeniz, Zehra / Saccomanno, Jacopo / Doehn, Jan-Moritz / Hübner, Ralf-Harto / Hinzmann, Bernd / Blüher, Anja / Siemann, Sandra / Telman, Dilduz / Suttorp, Norbert /

Witzenrath, Martin / Hippenstiel, Stefan / Skurk, Carsten / Poller, Wolfgang / Sander, Leif E / Beule, Dieter / Kurth, Florian / Guettouche, Toumy / Landmesser, Ulf / Berka, Jan / Luong, Khai / Rubelt, Florian / Heidecker, Bettina

EClinicalMedicine

2022 Band 48, Seite(n) 101438

Abstract: Background: Disease progression of subjects with coronavirus disease 2019 (COVID-19) varies dramatically. Understanding the various types of immune response to SARS-CoV-2 is critical for better clinical management of coronavirus outbreaks and to ... ...

Abstract	Background: Disease progression of subjects with coronavirus disease 2019 (COVID-19) varies dramatically. Understanding the various types of immune response to SARS-CoV-2 is critical for better clinical management of coronavirus outbreaks and to potentially improve future therapies. Disease dynamics can be characterized by deciphering the adaptive immune response. Methods: In this cross-sectional study we analyzed 117 peripheral blood immune repertoires from healthy controls and subjects with mild to severe COVID-19 disease to elucidate the interplay between B and T cells. We used an immune repertoire Primer Extension Target Enrichment method (immunoPETE) to sequence simultaneously human leukocyte antigen (HLA) restricted T cell receptor beta chain (TRB) and unrestricted T cell receptor delta chain (TRD) and immunoglobulin heavy chain (IgH) immune receptor repertoires. The distribution was analyzed of TRB, TRD and IgH clones between healthy and COVID-19 infected subjects. Using McFadden's Adjusted R2 variables were examined for a predictive model. The aim of this study is to analyze the influence of the adaptive immune repertoire on the severity of the disease (value on the World Health Organization Clinical Progression Scale) in COVID-19. Findings: Combining clinical metadata with clonotypes of three immune receptor heavy chains (TRB, TRD, and IgH), we found significant associations between COVID-19 disease severity groups and immune receptor sequences of B and T cell compartments. Logistic regression showed an increase in shared IgH clonal types and decrease of TRD in subjects with severe COVID-19. The probability of finding shared clones of TRD clonal types was highest in healthy subjects (controls). Some specific TRB clones seems to be present in severe COVID-19 (Figure S7b). The most informative models (McFadden´s Adjusted R2=0.141) linked disease severity with immune repertoire measures across all three cell types, as well as receptor-specific cell counts, highlighting the importance of multiple lymphocyte classes in disease progression. Interpretation: Adaptive immune receptor peripheral blood repertoire measures are associated with COVID-19 disease severity. Funding: The study was funded with grants from the Berlin Institute of Health (BIH).
Sprache	Englisch
Erscheinungsdatum	2022-05-14
Erscheinungsland	England
Dokumenttyp	Journal Article
ISSN	2589-5370
ISSN (online)	2589-5370
DOI	10.1016/j.eclinm.2022.101438
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Insight into bio-metal interface formation in vacuo: interplay of S-layer protein with copper and iron.

Makarova, Anna A / Grachova, Elena V / Neudachina, Vera S / Yashina, Lada V / Blüher, Anja / Molodtsov, Serguei L / Mertig, Michael / Ehrlich, Hermann / Adamchuk, Vera K / Laubschat, Clemens / Vyalikh, Denis V

Scientific reports

2015 Band 5, Seite(n) 8710

Abstract: The mechanisms of interaction between inorganic matter and biomolecules, as well as properties of resulting hybrids, are receiving growing interest due to the rapidly developing field of bionanotechnology. The majority of potential applications for metal- ...

Abstract	The mechanisms of interaction between inorganic matter and biomolecules, as well as properties of resulting hybrids, are receiving growing interest due to the rapidly developing field of bionanotechnology. The majority of potential applications for metal-biohybrid structures require stability of these systems under vacuum conditions, where their chemistry is elusive, and may differ dramatically from the interaction between biomolecules and metal ions in vivo. Here we report for the first time a photoemission and X-ray absorption study of the formation of a hybrid metal-protein system, tracing step-by-step the chemical interactions between the protein and metals (Cu and Fe) in vacuo. Our experiments reveal stabilization of the enol form of peptide bonds as the result of protein-metal interactions for both metals. The resulting complex with copper appears to be rather stable. In contrast, the system with iron decomposes to form inorganic species like oxide, carbide, nitride, and cyanide.
Mesh-Begriff(e)	Bacterial Proteins/chemistry ; Copper/chemistry ; Iron/chemistry ; Membrane Glycoproteins/chemistry ; Models, Chemical ; Oxidation-Reduction ; Photoelectron Spectroscopy ; Protein Binding ; Surface Properties ; Vacuum ; X-Ray Absorption Spectroscopy
Chemische Substanzen	Bacterial Proteins ; Membrane Glycoproteins ; S-layer proteins ; Copper (789U1901C5) ; Iron (E1UOL152H7)
Sprache	Englisch
Erscheinungsdatum	2015-03-04
Erscheinungsland	England
Dokumenttyp	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/srep08710
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Real-time study of the modification of the peptide bond by atomic calcium.

Kummer, Kurt / Vyalikh, Denis V / Blüher, Anja / Sivkov, Victor / Maslyuk, Volodymyr V / Bredow, Thomas / Mertig, Ingrid / Mertig, Michael / Molodtsov, Serguei L

The journal of physical chemistry. B

2011 Band 115, Heft 10, Seite(n) 2401–2407

Abstract: Strong chemical interaction between bacterial surface protein layers and calcium atoms deposited in situ on top was revealed by means of photoemission spectroscopy. The interaction appears to mainly happen at the oxygen site of the peptide bonds and ... ...

Abstract	Strong chemical interaction between bacterial surface protein layers and calcium atoms deposited in situ on top was revealed by means of photoemission spectroscopy. The interaction appears to mainly happen at the oxygen site of the peptide bonds and involves a large charge transfer from Ca 4s states into the peptide backbone. Chemical kinetics of this reaction was characterized using time-dependent valence band photoemission, and the reaction rate constant was determined.
Mesh-Begriff(e)	Bacillus ; Bacterial Proteins/chemistry ; Bacterial Proteins/metabolism ; Calcium/chemistry ; Calcium/metabolism ; Kinetics ; Models, Molecular ; Molecular Conformation ; Peptides/chemistry ; Photoelectron Spectroscopy
Chemische Substanzen	Bacterial Proteins ; Peptides ; Calcium (SY7Q814VUP)
Sprache	Englisch
Erscheinungsdatum	2011-03-17
Erscheinungsland	United States
Dokumenttyp	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1520-5207
ISSN (online)	1520-5207
DOI	10.1021/jp109555j
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Formation of tubes during self-assembly of bacterial surface layers.

Bobeth, Manfred / Blecha, Andreas / Blüher, Anja / Mertig, Michael / Korkmaz, Nuriye / Ostermann, Kai / Rödel, Gerhard / Pompe, Wolfgang

Langmuir : the ACS journal of surfaces and colloids

2011 Band 27, Heft 24, Seite(n) 15102–15111

Abstract: Based on experimental studies on tube formation during self-assembly of bacterial surface (S)-layers, a mechanistic model for describing the underlying basic mechanisms is proposed and the effect of process parameters on growth velocity and tube radius ... ...

Abstract	Based on experimental studies on tube formation during self-assembly of bacterial surface (S)-layers, a mechanistic model for describing the underlying basic mechanisms is proposed and the effect of process parameters on growth velocity and tube radius is investigated. The S-layer is modeled as a curved sheet with discrete binding sites for the association of monomers distributed along the S-layer edges. Reported changes of the tube radius owing to genetic protein modifications are explained within the framework of continuum mechanics. S-layer growth velocity and shape development are analyzed by Monte Carlo simulation in their dependence on the attachment and detachment frequencies of monomers at the S-layer. For curved S-layer patches, a criterion for the formation of S-layer tubes is derived. Accordingly, tubes can form only within a certain range of the initial monomer concentration. Furthermore, the effect of calcium ion concentration on tube formation is discussed, including recent experimental findings on the calcium effect.
Mesh-Begriff(e)	Bacillus/chemistry ; Bacillus/metabolism ; Biocompatible Materials/chemistry ; Biocompatible Materials/metabolism ; Calcium/metabolism ; Computer Simulation ; Geobacillus stearothermophilus/chemistry ; Geobacillus stearothermophilus/metabolism ; Hydrogen-Ion Concentration ; Membrane Glycoproteins/chemistry ; Membrane Glycoproteins/metabolism ; Membrane Glycoproteins/ultrastructure ; Microscopy, Electron, Scanning ; Monte Carlo Method ; Nanotechnology/methods ; Thermodynamics
Chemische Substanzen	Biocompatible Materials ; Membrane Glycoproteins ; S-layer proteins ; Calcium (SY7Q814VUP)
Sprache	Englisch
Erscheinungsdatum	2011-12-20
Erscheinungsland	United States
Dokumenttyp	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2005937-1
ISSN	1520-5827 ; 0743-7463
ISSN (online)	1520-5827
ISSN	0743-7463
DOI	10.1021/la203430q
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Increased risk of severe clinical course of COVID-19 in carriers of HLA-C*04:01.

Weiner, January / Suwalski, Phillip / Holtgrewe, Manuel / Rakitko, Alexander / Thibeault, Charlotte / Müller, Melina / Patriki, Dimitri / Quedenau, Claudia / Krüger, Ulrike / Ilinsky, Valery / Popov, Iaroslav / Balnis, Joseph / Jaitovich, Ariel / Helbig, Elisa T / Lippert, Lena J / Stubbemann, Paula / Real, Luis M / Macías, Juan / Pineda, Juan A /

Fernandez-Fuertes, Marta / Wang, Xiaomin / Karadeniz, Zehra / Saccomanno, Jacopo / Doehn, Jan-Moritz / Hübner, Ralf-Harto / Hinzmann, Bernd / Salvo, Mauricio / Blueher, Anja / Siemann, Sandra / Jurisic, Stjepan / Beer, Juerg H / Rutishauser, Jonas / Wiggli, Benedikt / Schmid, Hansruedi / Danninger, Kathrin / Binder, Ronald / Corman, Victor M / Mühlemann, Barbara / Arjun Arkal, Rao / Fragiadakis, Gabriela K / Mick, Eran / Comet, Consortium / Calfee, Carolyn S / Erle, David J / Hendrickson, Carolyn M / Kangelaris, Kirsten N / Krummel, Matthew F / Woodruff, Prescott G / Langelier, Charles R / Venkataramani, Urmila / García, Federico / Zyla, Joanna / Drosten, Christian / Alice, Braun / Jones, Terry C / Suttorp, Norbert / Witzenrath, Martin / Hippenstiel, Stefan / Zemojtel, Tomasz / Skurk, Carsten / Poller, Wolfgang / Borodina, Tatiana / Pa-Covid, Study Group / Ripke, Stephan / Sander, Leif E / Beule, Dieter / Landmesser, Ulf / Guettouche, Toumy / Kurth, Florian / Heidecker, Bettina

EClinicalMedicine

2021 Band 40, Seite(n) 101099

Abstract: Background: Since the beginning of the coronavirus disease 2019 (COVID-19) pandemic, there has been increasing urgency to identify pathophysiological characteristics leading to severe clinical course in patients infected with severe acute respiratory ... ...

Abstract	Background: Since the beginning of the coronavirus disease 2019 (COVID-19) pandemic, there has been increasing urgency to identify pathophysiological characteristics leading to severe clinical course in patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Human leukocyte antigen alleles (HLA) have been suggested as potential genetic host factors that affect individual immune response to SARS-CoV-2. We sought to evaluate this hypothesis by conducting a multicenter study using HLA sequencing. Methods: We analyzed the association between COVID-19 severity and HLAs in 435 individuals from Germany ( Findings: We describe a potential association of HLA-C04:01 with severe clinical course of COVID-19. Carriers of HLA-C04:01 had twice the risk of intubation when infected with SARS-CoV-2 (risk ratio 1.5 [95% CI 1.1-2.1], odds ratio 3.5 [95% CI 1.9-6.6], adjusted Interpretation: HLA-C04:01 carrier state is associated with severe clinical course in SARS-CoV-2. Our findings suggest that HLA class I alleles have a relevant role in immune defense against SARS-CoV-2. Funding:* Funded by Roche Sequencing Solutions, Inc.
Sprache	Englisch
Erscheinungsdatum	2021-09-02
Erscheinungsland	England
Dokumenttyp	Journal Article
ISSN	2589-5370
ISSN (online)	2589-5370
DOI	10.1016/j.eclinm.2021.101099
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: HLA-C* 04:01 is a Genetic Risk Allele for Severe Course of COVID-19

Weiner, January / Suwalski, Phillip / Holtgrewe, Manuel / Thibeault, Charlotte / Mueller, Melina / Patriki, Dimitri / Quedenau, Claudia / Krueger, Ulrike / Helbig, Elisa Theresa / Lippert, Lena / Stubbemann, Paula / Real, Luis Miguel / Sanchez, Juan Macias / Pineda, Juan A. / Fernandez-Fuertes, Marta / Wang, Xiaomin / Karadeniz, Zehra / Saccomanno, Jacopo / Doehn, Jan-Moritz /

Hubner, Ralf-Harto / Hinzmann, Bernd / Salvo, Mauricio / Blueher, Anja / Siemann, Sandra / Jurisic, Stjepan / Beer, Hansjuerg / Rutishauser, Jonas / Wiggli, Benedikt J. / Schmid, Hans Rudolf / Danninger, Kathrin / Binder, Ronald / Corman, Victor Max / Muehlemann, Barbara / Braun, Alice / Ripke, Stephan / Jones, Terry C. / Suttorp, Norbert / Witzenrath, Martin / Hippenstiel, Stefan / Zemojtel, Tomasz / Skurk, Carsten / Poller, Wolfgang / Borodina, Tatiana / Pa-COVID Study Group / Sander, Leif Erik / Beule, Dieter / Landmesser, Ulf / Guettouche, Toumy / Kurth, Florian / Heidecker, Bettina

medRxiv

Abstract: Background Since the beginning of the coronavirus disease 2019 (COVID-19) pandemic, there has been increasing demand to identify predictors of severe clinical course in patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). ... ...

Abstract	Background Since the beginning of the coronavirus disease 2019 (COVID-19) pandemic, there has been increasing demand to identify predictors of severe clinical course in patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Human leukocyte antigen alleles (HLA) have been suggested as potential genetic host factors. We sought to evaluate this hypothesis by conducting an international multicenter study using HLA sequencing with subsequent independent validation. Methods We analyzed a total of 332 samples. First, we enrolled 233 patients in Germany, Spain, and Switzerland for HLA and whole exome sequencing. Furthermore, we validated our results in a public data set (United States, n=99). Patients older than 18 years presenting with COVID-19 were included, representing the full spectrum of the disease. HLA candidate alleles were identified in the derivation cohort (n=92) and tested in two independent validation cohorts (n=240). Results We identified HLA-C* 04:01 as a novel genetic predictor for severe clinical course in COVID-19. Carriers of HLA-C* 04:01 had twice the risk of intubation when infected with SARS-CoV-2 (hazard ratio 2.1, adjusted p-value=0.0036). Importantly, these findings were successfully replicated in an independent data set. Furthermore, our findings are biologically plausible, as HLA-C* 04:01 has fewer predicted bindings sites with relevant SARS-CoV-2 peptides as compared to other HLA alleles. Exome sequencing confirmed findings from HLA analysis. Conclusions HLA-C* 04:01 carriage is associated with a twofold increased risk of intubation in patients infected with SARS-CoV-2. Testing for HLA-C* 04:01 could have clinical implications to identify high-risk patients and individualize management.
Schlagwörter	covid19
Sprache	Englisch
Erscheinungsdatum	2020-12-24
Verlag	Cold Spring Harbor Laboratory Press
Dokumenttyp	Artikel ; Online
DOI	10.1101/2020.12.21.20248121
Datenquelle	COVID19

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