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2. Tumor-associated macrophages trigger MAIT cell dysfunction at the HCC invasive margin

Author

Ruf, Benjamin, Bruhns, Matthias, Babaei, Sepideh, Kedei, Noemi, Ma, Lichun, Revsine, Mahler, Benmebarek, Mohamed-Reda, Ma, Chi, Heinrich, Bernd, Subramanyam, Varun, Qi, Jonathan, Wabitsch, Simon, Green, Benjamin L., Bauer, Kylynda C., Myojin, Yuta, Greten, Layla T., McCallen, Justin D., Huang, Patrick, Trehan, Rajiv, Wang, Xin, Nur, Amran, Murphy Soika, Dana Qiang, Pouzolles, Marie, Evans, Christine N., Chari, Raj, Kleiner, David E., Telford, William, Dadkhah, Kimia, Ruchinskas, Allison, Stovroff, Merrill K., Kang, Jiman, Oza, Kesha, Ruchirawat, Mathuros, Kroemer, Alexander, Wang, Xin Wei, Claassen, Manfred, Korangy, Firouzeh, and Greten, Tim F.

Published
2023
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3. Targeting extracellular and juxtamembrane FGFR2 mutations in chemotherapy-refractory cholangiocarcinoma

Author

Bitzer, Michael, Spahn, Stephan, Babaei, Sepideh, Horger, Marius, Singer, Stephan, Schulze-Osthoff, Klaus, Missios, Pavlos, Gatidis, Sergios, Nann, Dominik, Mattern, Sven, Scheble, Veit, Nikolaou, Konstantin, Armeanu-Ebinger, Sorin, Schulze, Martin, Schroeder, Christopher, Biskup, Saskia, Beha, Janina, Claassen, Manfred, Ruhm, Kristina, Poso, Antti, and Malek, Nisar P.

Published
2021
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4. High-dimensional in situ proteomics imaging to assess γδ T cells in spatial biology.

Author

Herold, Nicola, Bruhns, Matthias, Babaei, Sepideh, Spreuer, Janine, Castagna, Arianna, Yurttas, Can, Scheuermann, Sophia, Seitz, Christian, Ruf, Benjamin, Königsrainer, Alfred, Jurmeister, Philipp, Löffler, Markus W, Claassen, Manfred, and Wistuba-Hamprecht, Kilian

Subjects
T cells, CYTOLOGY, PROTEOMICS, COLON cancer, CANCER cells
Abstract

This study presents a high-dimensional immunohistochemistry approach to assess human γδ T cell subsets in their native tissue microenvironments at spatial resolution, a hitherto unmet scientific goal due to the lack of established antibodies and required technology. We report an integrated approach based on multiplexed imaging and bioinformatic analysis to identify γδ T cells, characterize their phenotypes, and analyze the composition of their microenvironment. Twenty-eight γδ T cell microenvironments were identified in tissue samples from fresh frozen human colon and colorectal cancer where interaction partners of the immune system, but also cancer cells were discovered in close proximity to γδ T cells, visualizing their potential contributions to cancer immunosurveillance. While this proof-of-principle study demonstrates the potential of this cutting-edge technology to assess γδ T cell heterogeneity and to investigate their microenvironment, future comprehensive studies are warranted to associate phenotypes and microenvironment profiles with features such as relevant clinical characteristics. Innate- and adaptive-like γδ T cell subsets, their phenotypic profile and neighborhood composition can be characterized by high-dimensional imaging. [ABSTRACT FROM AUTHOR]

Published
2024
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8. 1019 CSF1R+PD-L1+tumor-associated macrophages trigger MAIT cell dysfunction at the HCC invasive margin

Author

Ruf, Benjamin, primary, Bruhns, Matthias, additional, Babaei, Sepideh, additional, Kedei, Noemi, additional, Ma, Chi, additional, Ma, Lichun, additional, Revsine, Mahler, additional, Heinrich, Bernd, additional, Subramanyam, Varun, additional, Qi, Jonathan, additional, Wabitsch, Simon, additional, Green, Benjamin, additional, Bauer, Kylynda, additional, Myojin, Yuta, additional, Benmebarek, Mohamed-Reda, additional, Greten, Layla, additional, McCallen, Justin, additional, Huang, Patrick, additional, Pouzolles, Marie, additional, Kleiner, David, additional, Telford, William, additional, Dadkhah, Kimia, additional, Ruchinskas, Allison, additional, Stoffroff, Merrill, additional, Kang, Jiman, additional, Oza, Kesha, additional, Ruchirawat, Mathuros, additional, Kroemer, Alexander, additional, Wang, Xin, additional, Claassen, Manfred, additional, Korangy, Firouzeh, additional, and Greten, Tim, additional

Published
2022
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9. Integrating Protein Family Sequence Similarities with Gene Expression to Find Signature Gene Networks in Breast Cancer Metastasis

Author

Babaei, Sepideh, van den Akker, Erik, de Ridder, Jeroen, Reinders, Marcel, Hutchison, David, Series editor, Kanade, Takeo, Series editor, Kittler, Josef, Series editor, Kleinberg, Jon M., Series editor, Mattern, Friedemann, Series editor, Mitchell, John C., Series editor, Naor, Moni, Series editor, Nierstrasz, Oscar, Series editor, Pandu Rangan, C., Series editor, Steffen, Bernhard, Series editor, Sudan, Madhu, Series editor, Terzopoulos, Demetri, Series editor, Tygar, Doug, Series editor, Vardi, Moshe Y., Series editor, Weikum, Gerhard, Series editor, Istrail, Sorin, editor, Pevzner, Pavel, editor, Waterman, Michael S., editor, Loog, Marco, editor, Wessels, Lodewyk, editor, Reinders, Marcel J. T., editor, and de Ridder, Dick, editor

Published
2011
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10. Preexisting comorbidities shape the immune response associated with severe COVID-19

Author

Kreutmair, Stefanie, primary, Kauffmann, Manuel, additional, Unger, Susanne, additional, Ingelfinger, Florian, additional, Núñez, Nicolás Gonzalo, additional, Alberti, Chiara, additional, De Feo, Donatella, additional, Krishnarajah, Sinduya, additional, Friebel, Ekaterina, additional, Ulutekin, Can, additional, Babaei, Sepideh, additional, Gaborit, Benjamin, additional, Lutz, Mirjam, additional, Jurado, Nicole Puertas, additional, Malek, Nisar P., additional, Göpel, Siri, additional, Rosenberger, Peter, additional, Häberle, Helene A., additional, Ayoub, Ikram, additional, Al-Hajj, Sally, additional, Claassen, Manfred, additional, Liblau, Roland, additional, Martin-Blondel, Guillaume, additional, Bitzer, Michael, additional, Roquilly, Antoine, additional, and Becher, Burkhard, additional

Published
2022
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11. Dynamics of Melanoma-Associated Epitope-Specific CD8+ T Cells in the Blood Correlate With Clinical Outcome Under PD-1 Blockade

Author

Gaißler, Andrea, Meldgaard, Trine Sundebo, Heeke, Christina, Babaei, Sepideh, Tvingsholm, Siri Amanda, Bochem, Jonas, Spreuer, Janine, Amaral, Teresa, Wagner, Nikolaus Benjamin, Klein, Reinhild, Meier, Friedegund, Garbe, Claus, Eigentler, Thomas K., Pawelec, Graham, Claassen, Manfred, Weide, Benjamin, Hadrup, Sine Reker, and Wistuba-Hamprecht, Kilian

Subjects
SDG 3 - Good Health and Well-being, Checkpoint blockade, Immunology, T cells, Immunology and Allergy, Melanoma-associated antigen, Dextramer, Melanoma, Regression analysis
Abstract

Immune checkpoint blockade (ICB) is standard-of-care for patients with metastatic melanoma. It may re-invigorate T cells recognizing tumors, and several tumor antigens have been identified as potential targets. However, little is known about the dynamics of tumor antigen-specific T cells in the circulation, which might provide valuable information on ICB responses in a minimally invasive manner. Here, we investigated individual signatures composed of up to 167 different melanoma-associated epitope (MAE)-specific CD8+ T cells in the blood of stage IV melanoma patients before and during anti-PD-1 treatment, using a peptide-loaded multimer-based high-throughput approach. Additionally, checkpoint receptor expression patterns on T cell subsets and frequencies of myeloid-derived suppressor cells and regulatory T cells were quantified by flow cytometry. Regression analysis using the MAE-specific CD8+ T cell populations was applied to identify those that correlated with overall survival (OS). The abundance of MAE-specific CD8+ T cell populations, as well as their dynamics under therapy, varied between patients. Those with a dominant increase of these T cell populations during PD-1 ICB had a longer OS and progression-free survival than those with decreasing or balanced signatures. Patients with a dominantly increased MAE-specific CD8+ T cell signature also exhibited an increase in TIM-3+ and LAG-3+ T cells. From these results, we created a model predicting improved/reduced OS by combining data on dynamics of the three most informative MAE-specific CD8+ T cell populations. Our results provide insights into the dynamics of circulating MAE-specific CD8+ T cell populations during ICB, and should contribute to a better understanding of biomarkers of response and anti-cancer mechanisms.

Published
2022
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12. Abstract 2106: Spatially resolved immune cell atlas of human liver cancer identifies the cellular interaction network underlying mucosal-associated invariant T (MAIT) cell dysfunction in hepatocellular carcinoma

Author

Ruf, Benjamin, primary, Kedei, Noemi, additional, Bruhns, Matthias, additional, Babaei, Sepideh, additional, Heinrich, Bernd, additional, Subramanyam, Varun, additional, Ma, Chi, additional, Wabitsch, Simon, additional, Green, Benjamin, additional, Bauer, Kylynda C., additional, Myojin, Yuta, additional, Qi, Jonathan, additional, Nur, Amran, additional, McCallen, Justin, additional, Greten, Layla, additional, Telford, William G., additional, Stovroff, Merrill K., additional, Oza, Kesha, additional, Kang, Jiman, additional, Kroemer, Alexander, additional, Claassen, Manfred, additional, Korangy, Firouzeh, additional, and Greten, Tim F., additional

Published
2022
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13. ATRT-19. Functional genomics reveal distinct modulators of response to CDK4/6 inhibitors in ATRTs

Author

Merk, Daniel, primary, Hirsch, Sohpie, additional, Tsiami, Foteini, additional, Walter, Bianca, additional, Haeusser, Lara, additional, Babaei, Sepideh, additional, Admard, Jakob, additional, Casadei, Nicolas, additional, Roggia, Cristiana, additional, Spohn, Michael, additional, Schittenhelm, Jens, additional, Singer, Stephan, additional, Schüller, Ulrich, additional, Piccioni, Federica, additional, Persky, Nicole, additional, Root, David, additional, Claassen, Manfred, additional, Tatagiba, Marcos, additional, and Tabatabai, Ghazaleh, additional

Published
2022
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15. Distinct immunological signatures discriminate severe COVID-19 from non-SARS-CoV-2-driven critical pneumonia

Author

Kreutmair, Stefanie, primary, Unger, Susanne, additional, Núñez, Nicolás Gonzalo, additional, Ingelfinger, Florian, additional, Alberti, Chiara, additional, De Feo, Donatella, additional, Krishnarajah, Sinduya, additional, Kauffmann, Manuel, additional, Friebel, Ekaterina, additional, Babaei, Sepideh, additional, Gaborit, Benjamin, additional, Lutz, Mirjam, additional, Jurado, Nicole Puertas, additional, Malek, Nisar P., additional, Goepel, Siri, additional, Rosenberger, Peter, additional, Häberle, Helene A., additional, Ayoub, Ikram, additional, Al-Hajj, Sally, additional, Nilsson, Jakob, additional, Claassen, Manfred, additional, Liblau, Roland, additional, Martin-Blondel, Guillaume, additional, Bitzer, Michael, additional, Roquilly, Antoine, additional, and Becher, Burkhard, additional

Published
2022
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16. Abstract P021: Highly multiplexed spatial analysis of the HCC tumor immune microenvironment using CODEX imaging

Author

Ruf, Benjamin, primary, Kedei, Noemi, additional, Bruhns, Matthias, additional, Babaei, Sepideh, additional, Catania, Vanessa V., additional, Wabitsch, Simon, additional, Ma, Chi, additional, Heinrich, Bernd, additional, Subramanyam, Varun, additional, Stovroff, Merrill K., additional, Greten, Layla T., additional, Kroemer, Alexander, additional, Claassen, Manfred, additional, Greten, Tim F., additional, and Korangy, Firouzeh, additional

Published
2022
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17. EXTH-69. FUNCTIONAL GENOMICS UNCOVER GENETIC DEPENDENCIES IN ATRTS

Author

Merk, Daniel, primary, Hirsch, Sophie, additional, Tsiami, Foteini, additional, Walter, Bianca, additional, Haeusser, Lara, additional, Babaei, Sepideh, additional, Admard, Jakob, additional, Casadei, Nicolas, additional, Roggia, Cristiana, additional, Spohn, Michael, additional, Schittenhelm, Jens, additional, Singer, Stephan, additional, Schüller, Ulrich, additional, Piccioni, Federica, additional, Persky, Nicole, additional, Root, David, additional, Claassen, Manfred, additional, Tatagiba, Marcos, additional, and Tabatabai, Ghazaleh, additional

Published
2021
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20. Distinct immunological signatures discriminate severe COVID-19 from non-SARS-CoV-2-driven critical pneumonia

Author

Kreutmair, Stefanie, primary, Unger, Susanne, additional, Núñez, Nicolás Gonzalo, additional, Ingelfinger, Florian, additional, Alberti, Chiara, additional, De Feo, Donatella, additional, Krishnarajah, Sinduya, additional, Kauffmann, Manuel, additional, Friebel, Ekaterina, additional, Babaei, Sepideh, additional, Gaborit, Benjamin, additional, Lutz, Mirjam, additional, Jurado, Nicole Puertas, additional, Malek, Nisar P., additional, Goepel, Siri, additional, Rosenberger, Peter, additional, Häberle, Helene A., additional, Ayoub, Ikram, additional, Al-Hajj, Sally, additional, Nilsson, Jakob, additional, Claassen, Manfred, additional, Liblau, Roland, additional, Martin-Blondel, Guillaume, additional, Bitzer, Michael, additional, Roquilly, Antoine, additional, and Becher, Burkhard, additional

Published
2021
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21. Expression Quantitative Trait Locus Analysis in Systemic Sclerosis Identifies New Candidate Genes Associated With Multiple Aspects of Disease Pathology

Author

Kerick, Martin, González-Serna, David, Carnero-Montoro, Elena, Teruel, María, Acosta-Herrera, Marialbert, Makowska, Z., Buttgereit, Anne, Babaei, Sepideh, Barturen, Guillermo, López-Isac, Elena, PRECISESADS Clinical Consortium, Lesche, R., Beretta, L., Alarcón-Riquelme, M. E., and Martín, Javier

Subjects
0301 basic medicine, Adult, Male, Candidate gene, Immunology, Quantitative Trait Loci, Kruppel-Like Transcription Factors, Genome-wide association study, Single-nucleotide polymorphism, Disease, Biology, Bioinformatics, Polymorphism, Single Nucleotide, Pathogenesis, 03 medical and health sciences, Kruppel-Like Factor 4, 0302 clinical medicine, Rheumatology, Basic Helix-Loop-Helix Transcription Factors, Immunology and Allergy, Humans, Molecular Targeted Therapy, skin and connective tissue diseases, Transcription factor, Genetic Association Studies, Aged, 030203 arthritis & rheumatology, Scleroderma, Systemic, integumentary system, Nuclear Proteins, Middle Aged, DNA binding site, 030104 developmental biology, Gene Expression Regulation, Expression quantitative trait loci, Female, Inhibitor of Differentiation Proteins, T-Box Domain Proteins, Transcription Factors
Abstract

Objective: To identify the genetic variants that affect gene expression (expression quantitative trait loci [eQTLs]) in systemic sclerosis (SSc) and to investigate their role in the pathogenesis of the disease. Methods: We performed an eQTL analysis using whole-blood sequencing data from 333 SSc patients and 524 controls and integrated them with SSc genome-wide association study (GWAS) data. We integrated our findings from expression modeling, differential expression analysis, and transcription factor binding site enrichment with key clinical features of SSc. Results: We detected 49,123 validated cis-eQTLs from 4,539 SSc-associated single-nucleotide polymorphisms (SNPs) (PGWAS < 10-5 ). A total of 1,436 genes were within 1 Mb of the 4,539 SSc-associated SNPs. Of those 1,436 genes, 565 were detected as having ≥1 eQTL with an SSc-associated SNP. We developed a strategy to prioritize disease-associated genes based on their expression variance explained by SSc eQTLs (r2 > 0.05). As a result, 233 candidates were identified, 134 (58%) of them associated with hallmarks of SSc and 105 (45%) of them differentially expressed in the blood cells, skin, or lung tissue of SSc patients. Transcription factor binding site analysis revealed enriched motifs of 24 transcription factors (5%) among SSc eQTLs, 5 of which were found to be differentially regulated in the blood cells (ELF1 and MGA), skin (KLF4 and ID4), and lungs (TBX4) of SSc patients. Ten candidate genes (4%) can be targeted by approved medications for immune-mediated diseases, of which only 3 have been tested in clinical trials in patients with SSc. Conclusion: The findings of the present study indicate a new layer to the molecular complexity of SSc, contributing to a better understanding of the pathogenesis of the disease.

Published
2021

22. Integrative Analysis Reveals a Molecular Stratification of Systemic Autoimmune Diseases

Author

Barturen, Guillermo, Babaei, Sepideh, Català-Moll, Francesc, Martínez-Bueno, Manuel, Makowska, Zuzanna, Martorell-Marugán, Jordi, Carmona-Sáez, Pedro, Toro-Domínguez, Daniel, Carnero-Montoro, Elena, Teruel, María, Kerick, Martin, Acosta-Herrera, Marialbert, Le Lann, Lucas, Jamin, Christophe, Rodríguez-Ubreva, Javier, García-Gómez, Antonio, Kageyama, Jorge, Buttgereit, Anne, Hayat, Sikander, Mueller, Joerg, Lesche, Ralf, Hernández-Fuentes, María, Juárez, María, Rowley, Tania, López-Pedrera, Rosario, Ortega-Castro, Rafaela, Ortego-Centeno, N., Raya, Enrique, Artusi, Carolina, Benschop, Robert J., Chamberlain, Chris, Dow, Ernst R., Ioannou, Yiannis, Laigle, Laurence, Marovac, Jacqueline, Wojcik, Jerome, Renaudineau, Yves, Orietta Borghi, Maria, Frostegård, Johan, Martín, J., Beretta, Lorenzo, Ballestar, Estéban, McDonald, Fiona, Pers, J.O., and Alarcón-Riquelme, M. E.

Abstract

Objective Clinical heterogeneity, a hallmark of systemic autoimmune diseases, impedes early diagnosis and effective treatment, issues that may be addressed if patients could be classified into groups defined by molecular pattern. This study was undertaken to identify molecular clusters for reclassifying systemic autoimmune diseases independently of clinical diagnosis. Methods Unsupervised clustering of integrated whole blood transcriptome and methylome cross-sectional data on 955 patients with 7 systemic autoimmune diseases and 267 healthy controls was undertaken. In addition, an inception cohort was prospectively followed up for 6 or 14 months to validate the results and analyze whether or not cluster assignment changed over time. Results Four clusters were identified and validated. Three were pathologic, representing “inflammatory,” “lymphoid,” and “interferon” patterns. Each included all diagnoses and was defined by genetic, clinical, serologic, and cellular features. A fourth cluster with no specific molecular pattern was associated with low disease activity and included healthy controls. A longitudinal and independent inception cohort showed a relapse–remission pattern, where patients remained in their pathologic cluster, moving only to the healthy one, thus showing that the molecular clusters remained stable over time and that single pathogenic molecular signatures characterized each individual patient. Conclusion Patients with systemic autoimmune diseases can be jointly stratified into 3 stable disease clusters with specific molecular patterns differentiating different molecular disease mechanisms. These results have important implications for future clinical trials and the study of nonresponse to therapy, marking a paradigm shift in our view of systemic autoimmune diseases.

Published
2021

23. Integrative Analysis Reveals a Molecular Stratification of Systemic Autoimmune Diseases.

Author

UCL - SSS/IREC/RUMA - Pôle de Pathologies rhumatismales, UCL - (SLuc) Service de rhumatologie, Alarcón-Riquelme, Marta E, Benschop, Robert J, Balog, Attila, Bocskai, Márta, Deák, Magdolna, Dulic, Sonja, Kádár, Gabriella, Kovács, László, Cheng, Qingyu, Gerl, Velia, Hiepe, Falk, Khodadadi, Laleh, Thiel, Silvia, de Rinaldis, Emanuele, Rao, Sambasiva, Chamberlain, Chris, Dufour, Aleksandra, Dow, Ernst R, Ioannou, Yiannis, Laigle, Laurence, Marovac, Jacqueline, Wojcik, Jerome, Renaudineau, Yves, Borghi, Maria Orietta, Frostegård, Johan, Martín, Javier, Beretta, Lorenzo, Ballestar, Esteban, McDonald, Fiona, Pers, Jacques-Olivier, Wynar, Donatienne, Barturen, Guillermo, Babaei, Sepideh, Català-Moll, Francesc, Martínez-Bueno, Manuel, Makowska, Zuzanna, Martorell-Marugán, Jordi, Carmona-Sáez, Pedro, Toro-Domínguez, Daniel, Carnero-Montoro, Elena, Teruel, María, Kerick, Martin, Acosta-Herrera, Marialbert, Le Lann, Lucas, Jamin, Christophe, Rodríguez-Ubreva, Javier, García-Gómez, Antonio, Kageyama, Jorge, Buttgereit, Anne, Hayat, Sikander, Mueller, Joerg, Lesche, Ralf, Hernandez-Fuentes, Maria, Juarez, Maria, Rowley, Tania, White, Ian, Marañón, Concepción, Gomes Anjos, Tania, Varela, Nieves, Aguilar-Quesada, Rocío, Garrancho, Francisco Javier, López-Berrio, Antonio, Rodriguez Maresca, Manuel, Navarro-Linares, Héctor, Almeida, Isabel, Azevedo, Nancy, Brandão, Mariana, Campar, Ana, Faria, Raquel, Farinha, Fátima, Marinho, António, Neves, Esmeralda, Tavares, Ana, Vasconcelos, Carlos, Trombetta, Elena, Montanelli, Gaia, Vigone, Barbara, Alvarez-Errico, Damiana, Li, Tianlu, Thiagaran, Divya, Blanco Alonso, Ricardo, Corrales Martínez, Alfonso, Genre, Fernanda, López Mejías, Raquel, Gonzalez-Gay, Miguel A, Remuzgo, Sara, Ubilla Garcia, Begoña, Cervera, Ricard, Espinosa, Gerard, Rodríguez-Pintó, Ignasi, De Langhe, Ellen, Cremer, Jonathan, Lories, Rik, Belz, Doreen, Hunzelmann, Nicolas, Baerlecken, Niklas, Kniesch, Katja, Witte, Torsten, Lehner, Michaela, Stummvoll, Georg, Zauner, Michael, Aguirre-Zamorano, Maria Angeles, Barbarroja, Nuria, Castro-Villegas, Maria Carmen, Collantes-Estevez, Eduardo, de Ramon, Enrique, Díaz Quintero, Isabel, Escudero-Contreras, Alejandro, Fernández Roldán, María Concepción, Jiménez Gómez, Yolanda, Jiménez Moleón, Inmaculada, Lopez-Pedrera, Rosario, Ortega-Castro, Rafaela, Ortego, Norberto, Raya, Enrique, Artusi, Carolina, Gerosa, Maria, Meroni, Pier Luigi, Schioppo, Tommaso, De Groof, Aurélie, Ducreux, Julie, Lauwerys, Bernard, Maudoux, Anne-Lise, Cornec, Divi, Devauchelle-Pensec, Valérie, Jousse-Joulin, Sandrine, Jouve, Pierre-Emmanuel, Rouvière, Bénédicte, Saraux, Alain, Simon, Quentin, Alvarez, Montserrat, Chizzolini, Carlo, UCL - SSS/IREC/RUMA - Pôle de Pathologies rhumatismales, UCL - (SLuc) Service de rhumatologie, Alarcón-Riquelme, Marta E, Benschop, Robert J, Balog, Attila, Bocskai, Márta, Deák, Magdolna, Dulic, Sonja, Kádár, Gabriella, Kovács, László, Cheng, Qingyu, Gerl, Velia, Hiepe, Falk, Khodadadi, Laleh, Thiel, Silvia, de Rinaldis, Emanuele, Rao, Sambasiva, Chamberlain, Chris, Dufour, Aleksandra, Dow, Ernst R, Ioannou, Yiannis, Laigle, Laurence, Marovac, Jacqueline, Wojcik, Jerome, Renaudineau, Yves, Borghi, Maria Orietta, Frostegård, Johan, Martín, Javier, Beretta, Lorenzo, Ballestar, Esteban, McDonald, Fiona, Pers, Jacques-Olivier, Wynar, Donatienne, Barturen, Guillermo, Babaei, Sepideh, Català-Moll, Francesc, Martínez-Bueno, Manuel, Makowska, Zuzanna, Martorell-Marugán, Jordi, Carmona-Sáez, Pedro, Toro-Domínguez, Daniel, Carnero-Montoro, Elena, Teruel, María, Kerick, Martin, Acosta-Herrera, Marialbert, Le Lann, Lucas, Jamin, Christophe, Rodríguez-Ubreva, Javier, García-Gómez, Antonio, Kageyama, Jorge, Buttgereit, Anne, Hayat, Sikander, Mueller, Joerg, Lesche, Ralf, Hernandez-Fuentes, Maria, Juarez, Maria, Rowley, Tania, White, Ian, Marañón, Concepción, Gomes Anjos, Tania, Varela, Nieves, Aguilar-Quesada, Rocío, Garrancho, Francisco Javier, López-Berrio, Antonio, Rodriguez Maresca, Manuel, Navarro-Linares, Héctor, Almeida, Isabel, Azevedo, Nancy, Brandão, Mariana, Campar, Ana, Faria, Raquel, Farinha, Fátima, Marinho, António, Neves, Esmeralda, Tavares, Ana, Vasconcelos, Carlos, Trombetta, Elena, Montanelli, Gaia, Vigone, Barbara, Alvarez-Errico, Damiana, Li, Tianlu, Thiagaran, Divya, Blanco Alonso, Ricardo, Corrales Martínez, Alfonso, Genre, Fernanda, López Mejías, Raquel, Gonzalez-Gay, Miguel A, Remuzgo, Sara, Ubilla Garcia, Begoña, Cervera, Ricard, Espinosa, Gerard, Rodríguez-Pintó, Ignasi, De Langhe, Ellen, Cremer, Jonathan, Lories, Rik, Belz, Doreen, Hunzelmann, Nicolas, Baerlecken, Niklas, Kniesch, Katja, Witte, Torsten, Lehner, Michaela, Stummvoll, Georg, Zauner, Michael, Aguirre-Zamorano, Maria Angeles, Barbarroja, Nuria, Castro-Villegas, Maria Carmen, Collantes-Estevez, Eduardo, de Ramon, Enrique, Díaz Quintero, Isabel, Escudero-Contreras, Alejandro, Fernández Roldán, María Concepción, Jiménez Gómez, Yolanda, Jiménez Moleón, Inmaculada, Lopez-Pedrera, Rosario, Ortega-Castro, Rafaela, Ortego, Norberto, Raya, Enrique, Artusi, Carolina, Gerosa, Maria, Meroni, Pier Luigi, Schioppo, Tommaso, De Groof, Aurélie, Ducreux, Julie, Lauwerys, Bernard, Maudoux, Anne-Lise, Cornec, Divi, Devauchelle-Pensec, Valérie, Jousse-Joulin, Sandrine, Jouve, Pierre-Emmanuel, Rouvière, Bénédicte, Saraux, Alain, Simon, Quentin, Alvarez, Montserrat, and Chizzolini, Carlo

Abstract

OBJECTIVE: Clinical heterogeneity, a hallmark of systemic autoimmune diseases, impedes early diagnosis and effective treatment, issues that may be addressed if patients could be classified into groups defined by molecular pattern. This study was undertaken to identify molecular clusters for reclassifying systemic autoimmune diseases independently of clinical diagnosis. METHODS: Unsupervised clustering of integrated whole blood transcriptome and methylome cross-sectional data on 955 patients with 7 systemic autoimmune diseases and 267 healthy controls was undertaken. In addition, an inception cohort was prospectively followed up for 6 or 14 months to validate the results and analyze whether or not cluster assignment changed over time. RESULTS: Four clusters were identified and validated. Three were pathologic, representing "inflammatory," "lymphoid," and "interferon" patterns. Each included all diagnoses and was defined by genetic, clinical, serologic, and cellular features. A fourth cluster with no specific molecular pattern was associated with low disease activity and included healthy controls. A longitudinal and independent inception cohort showed a relapse-remission pattern, where patients remained in their pathologic cluster, moving only to the healthy one, thus showing that the molecular clusters remained stable over time and that single pathogenic molecular signatures characterized each individual patient. CONCLUSION: Patients with systemic autoimmune diseases can be jointly stratified into 3 stable disease clusters with specific molecular patterns differentiating different molecular disease mechanisms. These results have important implications for future clinical trials and the study of nonresponse to therapy, marking a paradigm shift in our view of systemic autoimmune diseases.

Published
2021

24. Distinct immunological signatures discriminate severe COVID-19 from non-SARS-CoV-2-driven critical pneumonia

Author

Kreutmair, Stefanie, Unger, Susanne, Núñez, Nicolás Gonzalo; https://orcid.org/0000-0003-3837-270X, Ingelfinger, Florian, Alberti, Chiara, De Feo, Donatella, Krishnarajah, Sinduya, Kauffmann, Manuel, Friebel, Ekaterina, Babaei, Sepideh, Gaborit, Benjamin, Lutz, Mirjam, Jurado, Nicole Puertas, Malek, Nisar P, Goepel, Siri, Rosenberger, Peter, Häberle, Helene A, Ayoub, Ikram, Al-Hajj, Sally, Nilsson, Jakob, Claassen, Manfred, Liblau, Roland, Martin-Blondel, Guillaume, Bitzer, Michael, Roquilly, Antoine, Becher, Burkhard, Kreutmair, Stefanie, Unger, Susanne, Núñez, Nicolás Gonzalo; https://orcid.org/0000-0003-3837-270X, Ingelfinger, Florian, Alberti, Chiara, De Feo, Donatella, Krishnarajah, Sinduya, Kauffmann, Manuel, Friebel, Ekaterina, Babaei, Sepideh, Gaborit, Benjamin, Lutz, Mirjam, Jurado, Nicole Puertas, Malek, Nisar P, Goepel, Siri, Rosenberger, Peter, Häberle, Helene A, Ayoub, Ikram, Al-Hajj, Sally, Nilsson, Jakob, Claassen, Manfred, Liblau, Roland, Martin-Blondel, Guillaume, Bitzer, Michael, Roquilly, Antoine, and Becher, Burkhard

Abstract

Immune profiling of COVID-19 patients has identified numerous alterations in both innate and adaptive immunity. However, whether those changes are specific to SARS-CoV-2 or driven by a general inflammatory response shared across severely ill pneumonia patients remains unknown. Here, we compared the immune profile of severe COVID-19 with non-SARS-CoV-2 pneumonia ICU patients using longitudinal, high-dimensional single-cell spectral cytometry and algorithm-guided analysis. COVID-19 and non-SARS-CoV-2 pneumonia both showed increased emergency myelopoiesis and displayed features of adaptive immune paralysis. However, pathological immune signatures suggestive of T cell exhaustion were exclusive to COVID-19. The integration of single-cell profiling with a predicted binding capacity of SARS-CoV-2 peptides to the patients' HLA profile further linked the COVID-19 immunopathology to impaired virus recognition. Toward clinical translation, circulating NKT cell frequency was identified as a predictive biomarker for patient outcome. Our comparative immune map serves to delineate treatment strategies to interfere with the immunopathologic cascade exclusive to severe COVID-19.

Published
2021

25. Integrative Analysis Reveals a Molecular Stratification of Systemic Autoimmune Diseases

Author

Barturen, Guillermo, primary, Babaei, Sepideh, additional, Català‐Moll, Francesc, additional, Martínez‐Bueno, Manuel, additional, Makowska, Zuzanna, additional, Martorell‐Marugán, Jordi, additional, Carmona‐Sáez, Pedro, additional, Toro‐Domínguez, Daniel, additional, Carnero‐Montoro, Elena, additional, Teruel, María, additional, Kerick, Martin, additional, Acosta‐Herrera, Marialbert, additional, Le Lann, Lucas, additional, Jamin, Christophe, additional, Rodríguez‐Ubreva, Javier, additional, García‐Gómez, Antonio, additional, Kageyama, Jorge, additional, Buttgereit, Anne, additional, Hayat, Sikander, additional, Mueller, Joerg, additional, Lesche, Ralf, additional, Hernandez‐Fuentes, Maria, additional, Juarez, Maria, additional, Rowley, Tania, additional, White, Ian, additional, Marañón, Concepción, additional, Gomes Anjos, Tania, additional, Varela, Nieves, additional, Aguilar‐Quesada, Rocío, additional, Garrancho, Francisco Javier, additional, López‐Berrio, Antonio, additional, Rodriguez Maresca, Manuel, additional, Navarro‐Linares, Héctor, additional, Almeida, Isabel, additional, Azevedo, Nancy, additional, Brandão, Mariana, additional, Campar, Ana, additional, Faria, Raquel, additional, Farinha, Fátima, additional, Marinho, António, additional, Neves, Esmeralda, additional, Tavares, Ana, additional, Vasconcelos, Carlos, additional, Trombetta, Elena, additional, Montanelli, Gaia, additional, Vigone, Barbara, additional, Alvarez‐Errico, Damiana, additional, Li, Tianlu, additional, Thiagaran, Divya, additional, Blanco Alonso, Ricardo, additional, Corrales Martínez, Alfonso, additional, Genre, Fernanda, additional, López Mejías, Raquel, additional, Gonzalez‐Gay, Miguel A., additional, Remuzgo, Sara, additional, Ubilla Garcia, Begoña, additional, Cervera, Ricard, additional, Espinosa, Gerard, additional, Rodríguez‐Pintó, Ignasi, additional, De Langhe, Ellen, additional, Cremer, Jonathan, additional, Lories, Rik, additional, Belz, Doreen, additional, Hunzelmann, Nicolas, additional, Baerlecken, Niklas, additional, Kniesch, Katja, additional, Witte, Torsten, additional, Lehner, Michaela, additional, Stummvoll, Georg, additional, Zauner, Michael, additional, Aguirre‐Zamorano, Maria Angeles, additional, Barbarroja, Nuria, additional, Castro‐Villegas, Maria Carmen, additional, Collantes‐Estevez, Eduardo, additional, Ramon, Enrique, additional, Díaz Quintero, Isabel, additional, Escudero‐Contreras, Alejandro, additional, Fernández Roldán, María Concepción, additional, Jiménez Gómez, Yolanda, additional, Jiménez Moleón, Inmaculada, additional, Lopez‐Pedrera, Rosario, additional, Ortega‐Castro, Rafaela, additional, Ortego, Norberto, additional, Raya, Enrique, additional, Artusi, Carolina, additional, Gerosa, Maria, additional, Meroni, Pier Luigi, additional, Schioppo, Tommaso, additional, De Groof, Aurélie, additional, Ducreux, Julie, additional, Lauwerys, Bernard, additional, Maudoux, Anne‐Lise, additional, Cornec, Divi, additional, Devauchelle‐Pensec, Valérie, additional, Jousse‐Joulin, Sandrine, additional, Jouve, Pierre‐Emmanuel, additional, Rouvière, Bénédicte, additional, Saraux, Alain, additional, Simon, Quentin, additional, Alvarez, Montserrat, additional, Chizzolini, Carlo, additional, Dufour, Aleksandra, additional, Wynar, Donatienne, additional, Balog, Attila, additional, Bocskai, Márta, additional, Deák, Magdolna, additional, Dulic, Sonja, additional, Kádár, Gabriella, additional, Kovács, László, additional, Cheng, Qingyu, additional, Gerl, Velia, additional, Hiepe, Falk, additional, Khodadadi, Laleh, additional, Thiel, Silvia, additional, Rinaldis, Emanuele, additional, Rao, Sambasiva, additional, Benschop, Robert J., additional, Chamberlain, Chris, additional, Dow, Ernst R., additional, Ioannou, Yiannis, additional, Laigle, Laurence, additional, Marovac, Jacqueline, additional, Wojcik, Jerome, additional, Renaudineau, Yves, additional, Borghi, Maria Orietta, additional, Frostegård, Johan, additional, Martín, Javier, additional, Beretta, Lorenzo, additional, Ballestar, Esteban, additional, McDonald, Fiona, additional, Pers, Jacques‐Olivier, additional, and Alarcón‐Riquelme, Marta E., additional

Published
2021
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26. Genome-wide CRISPR and small-molecule screens uncover targetable dependencies in ATRT

Author

Merk, Daniel J., primary, Hirsch, Sophie, additional, Tsiami, Foteini, additional, Walter, Bianca, additional, Haeusser, Lara A., additional, Babaei, Sepideh, additional, Admar, Jakob, additional, Casadei, Nicolas, additional, Roggia, Cristiana, additional, Spohn, Michael, additional, Schittenhelm, Jens, additional, Singer, Stephan, additional, Schüller, Ulrich, additional, Piccioni, Federica, additional, Persky, Nicole S., additional, Root, David E., additional, Claassen, Manfred, additional, Tatagiba, Marcos, additional, and Tabatabai, Ghazaleh, additional

Published
2020
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28. O31 Integrative analysis reveals a molecular stratification of systemic autoimmune diseases

Author

Barturen, Guillermo, primary, Babaei, Sepideh, additional, Català-Moll, Francesc, additional, Martínez-Bueno, Manuel, additional, Makowska, Zuzanna, additional, Martorell-Marugán, Jordi, additional, Carmona-Sáez, Pedro, additional, Toro-Domínguez, Daniel, additional, Carnero-Montoro, Elena, additional, Kerick, Martin, additional, Acosta-Herrera, Marialbert, additional, Lann, Lucas Le, additional, Jamin, Christophe, additional, Rodríguez-Ubreva, Javier, additional, García-Gómez, Antonio, additional, Kageyama, Jorge, additional, Buttgereit, Anne, additional, Hayat, Sikander, additional, Mueller, Joerg, additional, Lesche, Ralf, additional, Hernandez-Fuentes, Maria, additional, Juarez, Maria, additional, Rowley, Tania, additional, White, Ian, additional, Marañón, Concepción, additional, Anjos, Tania Gomes, additional, Varela, Nieves, additional, Aguilar-Quesada, Rocío, additional, Garrancho, Francisco Javier, additional, López-Berrio, Antonio, additional, Maresca, Manuel Rodriguez, additional, Navarro-Linares, Héctor, additional, Almeida, Isabel, additional, Azevedo, Nancy, additional, Brandão, Mariana, additional, Campar, Ana, additional, Faria, Raquel, additional, Farinha, Fátima, additional, Marinho, António, additional, Neves, Esmeralda, additional, Tavares, Ana, additional, Vasconcelos, Carlos, additional, Trombetta, Elena, additional, Montanelli, Gaia, additional, Vigone, Barbara, additional, Alvarez-Errico, Damiana, additional, Li, Tianlu, additional, Alonso, Ricardo Blanco, additional, Martínez, Alfonso Corrales, additional, Genre, Fernanda, additional, Mejías, Raquel López, additional, Gonzalez-Gay, Miguel A, additional, Remuzgo, Sara, additional, Garcia, Begoña Ubilla, additional, Cervera, Ricard, additional, Espinosa, Gerard, additional, Rodríguez-Pintó, Ignasi, additional, Langhe, Ellen De, additional, Cremer, Jonathan, additional, Lories, Rik, additional, Belz, Doreen, additional, Hunzelmann, Nicolas, additional, Baerlecken, Niklas, additional, Kniesch, Katja, additional, Witte, Torsten, additional, Lehner, Michaela, additional, Stummvoll, Georg, additional, Zauner, Michael, additional, Aguirre-Zamorano, Maria Angeles, additional, Barbarroja, Nuria, additional, Castro-Villegas, Maria Carmen, additional, Collantes-Estevez, Eduardo, additional, Ramon, Enrique de, additional, Quintero, Isabel Díaz, additional, Escudero-Contreras, Alejandro, additional, Roldán, María Concepción Fernández, additional, Gómez, Yolanda Jiménez, additional, Moleón, Inmaculada Jiménez, additional, Lopez-Pedrera, Rosario, additional, Ortega-Castro, Rafaela, additional, Ortego, Norberto, additional, Raya, Enrique, additional, Artusi, Carolina, additional, Gerosa, Maria, additional, Meroni, Pier Luigi, additional, Schioppo, Tommaso, additional, Groof, Aurélie De, additional, Ducreux, Julie, additional, Lauwerys, Bernard, additional, Maudoux, Anne-Lise, additional, Cornec, Divi, additional, Devauchelle-Pensec, Valérie, additional, Jousse-Joulin, Sandrine, additional, Jouve, Pierre-Emmanuel, additional, Rouvière, Bénédicte, additional, Saraux, Alain, additional, Simon, Quentin, additional, Alvarez, Montserrat, additional, Chizzolini, Carlo, additional, Dufour, Aleksandra, additional, Wynar, Donatienne, additional, Balog, Attila, additional, Bocskai, Márta, additional, Deák, Magdolna, additional, Dulic, Sonja, additional, Kádár, Gabriella, additional, Kovács, László, additional, Cheng, Qingyu, additional, Gerl, Velia, additional, Hiepe, Falk, additional, Khodadadi, Laleh, additional, Thiel, Silvia, additional, Rinaldis, Emanuele de, additional, Rao, Sambasiva, additional, Benschop, Robert J, additional, Chamberlain, Chris, additional, Dow, Ernst R, additional, Ioannou, Yiannis, additional, Laigle, Laurence, additional, Marovac, Jacqueline, additional, Wojcik, Jerome, additional, Renaudineau, Yves, additional, Borghi, Maria Orietta, additional, Frostegård, Johan, additional, Martín, Javier, additional, Beretta, Lorenzo, additional, Ballestar, Esteban, additional, McDonald, Fiona, additional, Pers, Jacques-Olivier, additional, and Alarcón-Riquelme, Marta E, additional

Published
2020
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29. Integrative Analysis Reveals a Molecular Stratification of Systemic Autoimmune Diseases

Author

Barturen, Guillermo, primary, Babaei, Sepideh, additional, Català-Moll, Francesc, additional, Martínez-Bueno, Manuel, additional, Makowska, Zuzanna, additional, Martorell-Marugán, Jordi, additional, Carmona-Sáez, Pedro, additional, Toro-Domínguez, Daniel, additional, Carnero-Montoro, Elena, additional, Teruel, María, additional, Kerick, Martin, additional, Acosta-Herrera, Marialbert, additional, Lann, Lucas Le, additional, Jamin, Christophe, additional, Rodríguez-Ubreva, Javier, additional, García-Gómez, Antonio, additional, Kageyama, Jorge, additional, Buttgereit, Anne, additional, Hayat, Sikander, additional, Mueller, Joerg, additional, Lesche, Ralf, additional, Hernandez-Fuentes, Maria, additional, Juarez, Maria, additional, Rowley, Tania, additional, White, Ian, additional, Marañón, Concepción, additional, Anjos, Tania Gomes, additional, Varela, Nieves, additional, Aguilar-Quesada, Rocío, additional, Garrancho, Francisco Javier, additional, López-Berrio, Antonio, additional, Maresca, Manuel Rodriguez, additional, Navarro-Linares, Héctor, additional, Almeida, Isabel, additional, Azevedo, Nancy, additional, Brandão, Mariana, additional, Campar, Ana, additional, Faria, Raquel, additional, Farinha, Fátima, additional, Marinho, António, additional, Neves, Esmeralda, additional, Tavares, Ana, additional, Vasconcelos, Carlos, additional, Trombetta, Elena, additional, Montanelli, Gaia, additional, Vigone, Barbara, additional, Alvarez-Errico, Damiana, additional, Li, Tianlu, additional, Alonso, Ricardo Blanco, additional, Martínez, Alfonso Corrales, additional, Genre, Fernanda, additional, López Mejías, Raquel, additional, Gonzalez-Gay, Miguel A., additional, Remuzgo, Sara, additional, Garcia, Begoña Ubilla, additional, Cervera, Ricard, additional, Espinosa, Gerard, additional, Rodríguez-Pintó, Ignasi, additional, De Langhe, Ellen, additional, Cremer, Jonathan, additional, Lories, Rik, additional, Belz, Doreen, additional, Hunzelmann, Nicolas, additional, Baerlecken, Niklas, additional, Kniesch, Katja, additional, Witte, Torsten, additional, Lehner, Michaela, additional, Stummvoll, Georg, additional, Zauner, Michael, additional, Aguirre-Zamorano, Maria Angeles, additional, Barbarroja, Nuria, additional, Castro-Villegas, Maria Carmen, additional, Collantes-Estevez, Eduardo, additional, de Ramon, Enrique, additional, Díaz Quintero, Isabel, additional, Escudero-Contreras, Alejandro, additional, Fernández Roldán, María Concepción, additional, Jiménez Gómez, Yolanda, additional, Jiménez Moleón, Inmaculada, additional, Lopez-Pedrera, Rosario, additional, Ortega-Castro, Rafaela, additional, Ortego, Norberto, additional, Raya, Enrique, additional, Artusi, Carolina, additional, Gerosa, Maria, additional, Meroni, Pier Luigi, additional, Schioppo, Tommaso, additional, De Groof, Aurélie, additional, Ducreux, Julie, additional, Lauwerys, Bernard, additional, Maudoux, Anne-Lise, additional, Cornec, Divi, additional, Devauchelle-Pensec, Valérie, additional, Jousse-Joulin, Sandrine, additional, Jouve, Pierre-Emmanuel, additional, Rouvière, Bénédicte, additional, Saraux, Alain, additional, Simon, Quentin, additional, Alvarez, Montserrat, additional, Chizzolini, Carlo, additional, Dufour, Aleksandra, additional, Wynar, Donatienne, additional, Balog, Attila, additional, Bocskai, Márta, additional, Deák, Magdolna, additional, Dulic, Sonja, additional, Kádár, Gabriella, additional, Kovács, László, additional, Cheng, Qingyu, additional, Gerl, Velia, additional, Hiepe, Falk, additional, Khodadadi, Laleh, additional, Thiel, Silvia, additional, de Rinaldis, Emanuele, additional, Rao, Sambasiva, additional, J.Benschop, Robert, additional, Chamberlain, Chris, additional, Dow, Ernst R., additional, Ioannou, Yiannis, additional, Laigle, Laurence, additional, Marovac, Jacqueline, additional, Wojcik, Jerome, additional, Renaudineau, Yves, additional, Borghi, Maria Orietta, additional, Frostegård, Johan, additional, Martín, Javier, additional, Beretta, Lorenzo, additional, Ballestar, Esteban, additional, McDonald, Fiona, additional, Pers, Jacques-Olivier, additional, and Alarcón-Riquelme, Marta E., additional

Published
2020
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30. EXPRESSION QUANTITATIVE TRAIT LOCI-EQTL- ANALYSIS IN SYSTEMIC SCLEROSIS

Author

Kerick, Martin, Gonzalez Serna, David, Teruel, María, Babaei, Sepideh, Acosta-Herrera, Marialbert, Carnero-Montoro, Elena, Makowska, Zuzanna, Buttgereit, Anne, Barturen, Guillermo, Hayat, Sikander, Kageyama, Jorge, Martínez-Bueno, Manuel, PRECISESADS Clinical Consortium, Lesche, Ralf, Alarcón-Riquelme, M. E., and Martín, Javier

Published
2019

31. TRANSCRIPTOME AND METHYLOME INTEGRATIVE MOLECULAR ANALYSIS UNCOVERS A NEW SYSTEMIC AUTOIMMUNE DISEASE CLASSIFICATION

Author

Barturen, Guillermo, Babaei, Sepideh, Català-Moll, Francesc, Makowska, Zuzanna, García-Gómez, Antonio, Buttgereit, Anne, Carnero-Montoro, Elena, Hayat, Sikander, Kerick, Martin, Charlon, Thomas, Gemperline, David C., Le Lann, Lucas, Quirantes-PIné, Rosa, Borrás-Linares, Isabel, Kageyama, Jorge, Rodríguez-Ubreva, Javier, Fernández-Ochoa, Alvaro, Carmona Sanz, Pedro, Jamin, Christophe, Lesche, Ralf, Benschop, Robert J., Chamberlain, Chris, Dow, Ernst R., Gomes, Tania, Juárez, María, Laigle, Laurence, Marovac, Jacqueline, MacDonald, Fiona, Wojcik, Jerome, Ballestar, Estéban, Beretta, Lorenzo, Borghi, Maria Orietta, Frostegård, Johan, García, María Luisa, Martín, J., Pers, Jacques-Olivier, Renadineau, Yves, Segura Carretero, Antonio, and Alarcón-Riquelme, Marta

Published
2019

32. Synthesis and characterization of polyindole/silver nanoparticles nanocomposite and its application in the design of electrochemical sensor L-Cysteine

Author

Ghanbari, Khadijeh, Babaei, Zahra, and Babaei, Sepideh

Subjects
Sensor, Glassy carbon electrode, L-cysteine, Polyindole, Silver nanoparticl
Abstract

In this study, an effective electrochemical sensor for the rapid measurement of L-cysteine based on glassy carbon electrode modifed with polyindole/silver nanoparticles nanocomposite is presented. Polyindole nanofbers were synthesized by cyclic voltammetry method at the glassy carbon electrode surface, and then silver nanoparticles were deposited on these nanofbers using a constant potential method. Surface morphology and characterization of the modifed electrodes were confrmed by feld emission scanning microscopy (FE-SEM), X-ray diffraction (XRD), Raman, and FT-IR spectroscopies. The electrochemical investigation showed that the polyindole/ silver nanoparticles had very good effciency with respect to the electrocatalytic oxidation of L-cysteine in phosphate buffer solution (pH = 7.0). The response of the glassy carbon electrode/ polyindole/silver nanoparticles to L-cysteine was linear in the concentration range of 0.01-10 mM. The detection limit was obtained at signal/noise=3, 5.7 μM. In addition, the sensor showed good stability and repeatability. The application of the proposed sensor for the analysis of L-cysteine in human serum was successful., In this study, an effective electrochemical sensor for the rapid measurement of L-cysteine based on glassy carbon electrode modifed with polyindole/silver nanoparticles nanocomposite is presented.

Published
2018
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33. Intrarenal activation of adaptive immune effectors is associated with tubular damage and impaired renal function in lupus nephritis

Author

Pamfil, Cristina, Makowska, Zuzanna, de Groof, Aurélie, Tilman, Gaëlle, Babaei, Sepideh, Galant, Christine, Montigny, Pauline, Demoulin, Nathalie, Jadoul, Michel, Aydin, Selda, Lesche, Ralf, Mcdonald, Fiona, Houssiau, Frédéric, Lauwerys, Bernard, Pers, J.O., Pharmaceuticals Division Bayer Pharma Aktiengesellschaft, Université Catholique de Louvain = Catholic University of Louvain (UCL), Cliniques Universitaires Saint-Luc [Bruxelles], Bayer Pharma AG [Berlin], CIC Brest, Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital de la Cavale Blanche, and Calvez, Ghislaine

Subjects
[SDV] Life Sciences [q-bio], [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, [SDV]Life Sciences [q-bio], ComputingMilieux_MISCELLANEOUS, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

International audience

Published
2018

34. Transcriptome and Methylome Integrative Molecular Analysis Uncovers a New Systemic Autoimmune Disease Classification

Author

Barturen, Guillermo, Babaei, Sepideh, Catala-Moll, Francesc, Makowska, Zuzanna, García-Gómez, Antonio, Buttgereit, Anne, Carnero-Montoro, Elena, Hayat, Sikander, Kerick, Martin, Charlon, Thomas, Gemperline, David C, Le Lann, Lucas, Quirantes-PIné, Rosa, Borrás-Linares, Isabel, Muchmore, Brian, Kageyama, Jorge, Rodríguez-Ubreva, Javier, Fernández-Ochoa, Alvaro, Carmona Sanz, Pedro, Jamin, Christophe, Lesche, Ralf, Benschop, Robert J, Chamberlain, Chris, Dow, Ernst R, Gomes, Tania Cristina, Juárez, Maria, Laigle, Laurence, Marovac, Jacqueline, Macdonald, Fiona, Wojcik, Jérôme, Ballestar, Esteban, Beretta, Lorenzo, Borghi, Maria Orietta, Frostegård, Johan, Garcia, Maria Luisa, Martin, Javier, Pers, Jacques-Olivier, Renadineau, Yves, Segura Carretero, Antonio, Alarcón-Riquelme, Marta, Centre for Genomics and Oncological Reearch (GENYO), Pharmaceuticals Division Bayer Pharma Aktiengesellschaft, Institut d' Investigacions Biomediques Bellvitge (IDIBELL), Programa de Epigenètica y Biología del Cáncer-PEBC, Bayer Pharma AG [Berlin], Instituto de Parasitología y Biomedicina 'López-Neyra', Quartzbio, Geneva, Eli Lilly & Company, Lymphocyte B et Auto-immunité (LBAI), Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Analytical Chemistry, Granada, University of Granada [Granada], Eli Lilly, Indianapolis, USA, UCB Pharma Slough, Cancer Epigenetics and Biology Program-PEBC, Institut d'Investigació Biomèdica de Bellvitge [Barcelone] (IDIBELL), Scleroderma Unit, Referral Center for Systemic Autoimmune Diseases, Fondazione IRCCS Istituto Nazionale Tumori - National Cancer Institute [Milan], IRCCS Istituto Auxologico Italiano, Unit for Chronic Inflammatory Diseases, Institute for Environmental Medicine, Karolinska Institutet [Stockholm], The Andalusian Center for Nanomedicine and Biotechnology (BIONAND), Institute of Parasitology and Biomedicine (IPB - GRANADA), Spanish National Research Council (CSIC), LabEX IGO Immunothérapie Grand Ouest, Laboratoire d'Immunologie et Immunothérapie [Brest], Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), and Université de Brest (UBO)

Subjects
[SDV]Life Sciences [q-bio], ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2018

36. Intrarenal activation of adaptive immune effectors is associated with tubular damage and impaired renal function in lupus nephritis.

Author

UCL - SSS/IREC/MONT - Pôle Mont Godinne, UCL - SSS/IREC/NEFR - Pôle de Néphrologie, UCL - SSS/IREC/MORF - Pôle de Morphologie, UCL - SSS/IREC/SLUC - Pôle St.-Luc, UCL - SSS/IREC/RUMA - Pôle de Pathologies rhumatismales, UCL - (SLuc) Service de rhumatologie, UCL - (SLuc) Service d'anatomie pathologique, UCL - (SLuc) Service de néphrologie, UCL - (MGD) Service de néphrologie, Pamfil, Cristina, Makowska, Zuzanna, De Groof, Aurélie, Tilman, Gaëlle, Babaei, Sepideh, Galant, Christine, Montigny, Pauline, Demoulin, Nathalie, Jadoul, Michel, Aydin, Selda, Lesche, Ralf, McDonald, Fiona, Houssiau, Frédéric, Lauwerys, Bernard, UCL - SSS/IREC/MONT - Pôle Mont Godinne, UCL - SSS/IREC/NEFR - Pôle de Néphrologie, UCL - SSS/IREC/MORF - Pôle de Morphologie, UCL - SSS/IREC/SLUC - Pôle St.-Luc, UCL - SSS/IREC/RUMA - Pôle de Pathologies rhumatismales, UCL - (SLuc) Service de rhumatologie, UCL - (SLuc) Service d'anatomie pathologique, UCL - (SLuc) Service de néphrologie, UCL - (MGD) Service de néphrologie, Pamfil, Cristina, Makowska, Zuzanna, De Groof, Aurélie, Tilman, Gaëlle, Babaei, Sepideh, Galant, Christine, Montigny, Pauline, Demoulin, Nathalie, Jadoul, Michel, Aydin, Selda, Lesche, Ralf, McDonald, Fiona, Houssiau, Frédéric, and Lauwerys, Bernard

Abstract

OBJECTIVES: Chronic renal impairment remains a feared complication of lupus nephritis (LN). The present work aimed at identifying mechanisms and markers of disease severity in renal tissue samples from patients with LN. METHODS: We performed high-throughput transcriptomic studies (Illumina HumanHT-12 v4 Expression BeadChip) on archived kidney biopsies from 32 patients with LN and eight controls (pretransplant donors). Histological staging (glomerular and tubular scores) and immunohistochemistry experiments were performed on the same and on a replication set of 37 LN kidney biopsy samples. RESULTS: A group of LN samples was identified by unsupervised clustering studies based on their gene expression features, that is, the overexpression of transcripts involved in antigen presentation, T and B cell activation. These samples were characterised by a significantly lower estimated glomerular filtration rate (eGFR) at the time of biopsy (T0) compared with the other systemic lupus erythematosus samples. Yet, apparent disease duration at T0, double-stranded DNA antibody titres at T0 and other relevant characteristics (serum C3, proteinuria, histological scores, numbers of previous flares) were not different between groups.Immunohistochemistry studies confirmed the association between interstitial infiltration by adaptive immune effectors and decreased renal function in the same and in a replication group of LN kidney biopsies. This was associated with transcriptomic, histological and immunohistochemical evidence of renal tubular cell involvement. CONCLUSION: Interstitial infiltration of LN kidney biopsies by adaptive immune effectors is associated with impaired renal tubular cell function and decreased eGFR. These results open new perspectives in evaluating and treating patients with LN, focusing on intrarenal mechanisms of immune cell activation.

Published
2018

45. Integration of gene expression and DNAmethylation profiles improves molecular subtype classification in acute myeloid leukemia.

Author

Taskesen, Erdogan, Babaei, Sepideh, Reinders, Marcel M. J., and de Ridder, Jeroen

Abstract

Background: Acute Myeloid Leukemia (AML) is characterized by various cytogenetic and molecular abnormalities. Detection of these abnormalities is important in the risk-classification of patients but requires laborious experimentation. Various studies showed that gene expression profiles (GEP), and the gene signatures derived from GEP, can be used for the prediction of subtypes in AML. Similarly, successful prediction was also achieved by exploiting DNA-methylation profiles (DMP). There are, however, no studies that compared classification accuracy and performance between GEP and DMP, neither are there studies that integrated both types of data to determine whether predictive power can be improved. Approach: Here, we used 344 well-characterized AML samples for which both gene expression and DNAmethylation profiles are available. We created three different classification strategies including early, late and no integration of these datasets and used them to predict AML subtypes using a logistic regression model with Lasso regularization. Results: We illustrate that both gene expression and DNA-methylation profiles contain distinct patterns that contribute to discriminating AML subtypes and that an integration strategy can exploit these patterns to achieve synergy between both data types. We show that concatenation of features from both data sets, i.e. early integration, improves the predictive power compared to classifiers trained on GEP or DMP alone. A more sophisticated strategy, i.e. the late integration strategy, employs a two-layer classifier which outperforms the early integration strategy. Conclusion: We demonstrate that prediction of known cytogenetic and molecular abnormalities in AML can be further improved by integrating GEP and DMP profiles. [ABSTRACT FROM AUTHOR]

Published
2015
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46. Distinct immunological signatures discriminate severe COVID-19 from non-SARS-CoV-2-driven critical pneumonia

Author

Kreutmair, Stefanie, Unger, Susanne, Núñez, Nicolás Gonzalo, Ingelfinger, Florian, Alberti, Chiara, De Feo, Donatella, Krishnarajah, Sinduya, Kauffmann, Manuel, Friebel, Ekaterina, Babaei, Sepideh, Gaborit, Benjamin, Lutz, Mirjam, Jurado, Nicole Puertas, Malek, Nisar P, Goepel, Siri, Rosenberger, Peter, Häberle, Helene A, Ayoub, Ikram, Al-Hajj, Sally, Nilsson, Jakob, Claassen, Manfred, Liblau, Roland, Martin-Blondel, Guillaume, Bitzer, Michael, Roquilly, Antoine, and Becher, Burkhard

Subjects
3. Good health

47. Expression Quantitative Trait Locus Analysis in Systemic Sclerosis Identifies New Candidate Genes Associated With Multiple Aspects of Disease Pathology.

Author

Kerick M, González-Serna D, Carnero-Montoro E, Teruel M, Acosta-Herrera M, Makowska Z, Buttgereit A, Babaei S, Barturen G, López-Isac E, Lesche R, Beretta L, Alarcon-Riquelme ME, and Martin J

Subjects
Adult, Aged, Basic Helix-Loop-Helix Transcription Factors genetics, Female, Genetic Association Studies, Humans, Inhibitor of Differentiation Proteins genetics, Kruppel-Like Factor 4, Kruppel-Like Transcription Factors genetics, Male, Middle Aged, Molecular Targeted Therapy, Nuclear Proteins genetics, Polymorphism, Single Nucleotide, Quantitative Trait Loci, T-Box Domain Proteins genetics, Transcription Factors genetics, Gene Expression Regulation genetics, Scleroderma, Systemic genetics
Abstract

Objective: To identify the genetic variants that affect gene expression (expression quantitative trait loci [eQTLs]) in systemic sclerosis (SSc) and to investigate their role in the pathogenesis of the disease., Methods: We performed an eQTL analysis using whole-blood sequencing data from 333 SSc patients and 524 controls and integrated them with SSc genome-wide association study (GWAS) data. We integrated our findings from expression modeling, differential expression analysis, and transcription factor binding site enrichment with key clinical features of SSc., Results: We detected 49,123 validated cis-eQTLs from 4,539 SSc-associated single-nucleotide polymorphisms (SNPs) (P GWAS < 10 -5 ). A total of 1,436 genes were within 1 Mb of the 4,539 SSc-associated SNPs. Of those 1,436 genes, 565 were detected as having ≥1 eQTL with an SSc-associated SNP. We developed a strategy to prioritize disease-associated genes based on their expression variance explained by SSc eQTLs (r 2 > 0.05). As a result, 233 candidates were identified, 134 (58%) of them associated with hallmarks of SSc and 105 (45%) of them differentially expressed in the blood cells, skin, or lung tissue of SSc patients. Transcription factor binding site analysis revealed enriched motifs of 24 transcription factors (5%) among SSc eQTLs, 5 of which were found to be differentially regulated in the blood cells (ELF1 and MGA), skin (KLF4 and ID4), and lungs (TBX4) of SSc patients. Ten candidate genes (4%) can be targeted by approved medications for immune-mediated diseases, of which only 3 have been tested in clinical trials in patients with SSc., Conclusion: The findings of the present study indicate a new layer to the molecular complexity of SSc, contributing to a better understanding of the pathogenesis of the disease., (© 2021, American College of Rheumatology.)

Published
2021
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48. Intrarenal activation of adaptive immune effectors is associated with tubular damage and impaired renal function in lupus nephritis.

Author

Pamfil C, Makowska Z, De Groof A, Tilman G, Babaei S, Galant C, Montigny P, Demoulin N, Jadoul M, Aydin S, Lesche R, McDonald F, Houssiau FA, and Lauwerys BR

Subjects
Adult, Female, Humans, Kidney Tubules pathology, Male, Renal Insufficiency immunology, Renal Insufficiency pathology, Transcriptome, Lupus Nephritis immunology, Lupus Nephritis pathology
Abstract

Objectives: Chronic renal impairment remains a feared complication of lupus nephritis (LN). The present work aimed at identifying mechanisms and markers of disease severity in renal tissue samples from patients with LN., Methods: We performed high-throughput transcriptomic studies (Illumina HumanHT-12 v4 Expression BeadChip) on archived kidney biopsies from 32 patients with LN and eight controls (pretransplant donors). Histological staging (glomerular and tubular scores) and immunohistochemistry experiments were performed on the same and on a replication set of 37 LN kidney biopsy samples., Results: A group of LN samples was identified by unsupervised clustering studies based on their gene expression features, that is, the overexpression of transcripts involved in antigen presentation, T and B cell activation. These samples were characterised by a significantly lower estimated glomerular filtration rate (eGFR) at the time of biopsy (T0) compared with the other systemic lupus erythematosus samples. Yet, apparent disease duration at T0, double-stranded DNA antibody titres at T0 and other relevant characteristics (serum C3, proteinuria, histological scores, numbers of previous flares) were not different between groups.Immunohistochemistry studies confirmed the association between interstitial infiltration by adaptive immune effectors and decreased renal function in the same and in a replication group of LN kidney biopsies. This was associated with transcriptomic, histological and immunohistochemical evidence of renal tubular cell involvement., Conclusion: Interstitial infiltration of LN kidney biopsies by adaptive immune effectors is associated with impaired renal tubular cell function and decreased eGFR. These results open new perspectives in evaluating and treating patients with LN, focusing on intrarenal mechanisms of immune cell activation., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY. Published by BMJ.)

Published
2018
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49. Highlights from the Third International Society for Computational Biology (ISCB) European Student Council Symposium 2014.

Author

Francescatto M, Hermans SM, Babaei S, Vicedo E, Borrel A, and Meysman P

Subjects
Awards and Prizes, Databases, Factual, Gene Regulatory Networks, Models, Statistical, Peer Review, Research, Computational Biology
Abstract

In this meeting report, we give an overview of the talks, presentations and posters presented at the third European Symposium of the International Society for Computational Biology (ISCB) Student Council. The event was organized as a satellite meeting of the 13th European Conference for Computational Biology (ECCB) and took place in Strasbourg, France on September 6th, 2014.

Published
2015
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