16 results on '"Heyn H"'
Search Results
2. 561P Liquid biopsy tracking of immunotherapy-induced T cell dynamics in MSS colorectal and endometrial tumors.
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Heyn, H., Melero, J.L., Deuner, G., Argota, I. Baraibar, Grzelak, M., Caratu, G., Duran, C. Garcia, Béjar, J.F. Grau, Illescas, D.G., Madrid, L. Fariñas, Nieto, P., Morabito, S., Rotem, A., Casbas-Hernandez, P., Gros, A., Tabernero, J., Oaknin, A., Sachica, J.N., Borcherding, N., and Fernandez, M.E. Elez
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- 2024
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3. 268P Impact of B cell and plasma cell infiltration on survival in early-stage breast cancer (BC) without recurrence.
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Angelats, L., Brunet, L. Pare, Rubio-Perez, C., Torres, E. Sanfeliu, Solis, E. Segui, Villacampa, G., Marin, M., Conte, B., Saez, O. Martinez, Fernandez-Martinez, A., Buckingham, W., Guedan, S., Heyn, H., Vivancos, A., Parker, J., Gonzalez, P. Villagrasa, Perou, C.M., Prat, A., and Maristany, F. Braso
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- 2024
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4. Spatiotemporal omics for biology and medicine.
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Liu L, Chen A, Li Y, Mulder J, Heyn H, and Xu X
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- Humans, Animals, Proteomics, Genomics
- Abstract
The completion of the Human Genome Project has provided a foundational blueprint for understanding human life. Nonetheless, understanding the intricate mechanisms through which our genetic blueprint is involved in disease or orchestrates development across temporal and spatial dimensions remains a profound scientific challenge. Recent breakthroughs in cellular omics technologies have paved new pathways for understanding the regulation of genomic elements and the relationship between gene expression, cellular functions, and cell fate determination. The advent of spatial omics technologies, encompassing both imaging and sequencing-based methodologies, has enabled a comprehensive understanding of biological processes from a cellular ecosystem perspective. This review offers an updated overview of how spatial omics has advanced our understanding of the translation of genetic information into cellular heterogeneity and tissue structural organization and their dynamic changes over time. It emphasizes the discovery of various biological phenomena, related to organ functionality, embryogenesis, species evolution, and the pathogenesis of diseases., Competing Interests: Declaration of interests X.X., L.L., A.C., and Y.L. are the co-inventors of Stereo-seq technology. The chip, procedure, and applications of Stereo-seq are covered in pending patents., (Copyright © 2024 Elsevier Inc. All rights reserved.)
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- 2024
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5. Systematic mapping of organism-scale gene-regulatory networks in aging using population asynchrony.
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Eder M, Martin OMF, Oswal N, Sedlackova L, Moutinho C, Del Carmen-Fabregat A, Menendez Bravo S, Sebé-Pedrós A, Heyn H, and Stroustrup N
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- Animals, Caenorhabditis elegans Proteins metabolism, Caenorhabditis elegans Proteins genetics, RNA, Messenger metabolism, RNA, Messenger genetics, Caenorhabditis elegans genetics, Caenorhabditis elegans physiology, Aging genetics, Gene Regulatory Networks, Transcriptome genetics, Longevity genetics
- Abstract
In aging, physiologic networks decline in function at rates that differ between individuals, producing a wide distribution of lifespan. Though 70% of human lifespan variance remains unexplained by heritable factors, little is known about the intrinsic sources of physiologic heterogeneity in aging. To understand how complex physiologic networks generate lifespan variation, new methods are needed. Here, we present Asynch-seq, an approach that uses gene-expression heterogeneity within isogenic populations to study the processes generating lifespan variation. By collecting thousands of single-individual transcriptomes, we capture the Caenorhabditis elegans "pan-transcriptome"-a highly resolved atlas of non-genetic variation. We use our atlas to guide a large-scale perturbation screen that identifies the decoupling of total mRNA content between germline and soma as the largest source of physiologic heterogeneity in aging, driven by pleiotropic genes whose knockdown dramatically reduces lifespan variance. Our work demonstrates how systematic mapping of physiologic heterogeneity can be applied to reduce inter-individual disparities in aging., Competing Interests: Declaration of interests H.H. is co-founder of Omniscope and scientific advisory board member of MiRXES. C.M. is scientific consultant member of GLG., (Copyright © 2024 Elsevier Inc. All rights reserved.)
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- 2024
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6. Decoding the muscle transcriptome of patients with late onset Pompe disease reveals markers of disease progression.
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Monceau A, Gokul Nath R, Suárez-Calvet X, Musumeci O, Toscano A, Kierdaszuk B, Kostera-Pruszczyk A, Domínguez-González C, Hernández-Lain A, Paradas C, Rivas E, Papadimas G, Papadopoulos C, Chrysanthou-Piterou M, Gallardo E, Olivé M, Lilleker J, Roberts ME, Marchese D, Lunazzi G, Heyn H, Fernández-Simón E, Villalobos E, Clark J, Katsikis P, Collins C, Mehra P, Laidler Z, Vincent A, Tasca G, Marini-Bettolo C, Guglieri M, Straub V, Raben N, and Díaz-Manera J
- Abstract
Late-onset Pompe Disease (LOPD) is a rare genetic disorder caused by the deficiency of acid alpha-glucosidase leading to progressive cellular dysfunction due to the accumulation of glycogen in the lysosome. The mechanism of relentless muscle damage - a classic manifestation of the disease - has been extensively studied by analysing the whole muscle tissue; however, little, if any, is known about transcriptional heterogeneity among nuclei within the multinucleated skeletal muscle cells. This is the first report of application of single nuclei RNA sequencing to uncover changes in the gene expression profile in muscle biopsies from eight patients with LOPD and four muscle samples from age and gender matched healthy controls. We matched these changes with histology findings using GeoMx Spatial Transcriptomics to compare the transcriptome of control myofibers from healthy individuals with non-vacuolated (histologically unaffected) and vacuolated (histologically affected) myofibers of LODP patients. We observed an increase in the proportion of slow and regenerative muscle fibers and macrophages in LOPD muscles. The expression of the genes involved in glycolysis was reduced, whereas the expression of the genes involved in the metabolism of lipids and amino acids was increased in non-vacuolated fibers, indicating early metabolic abnormalities. Additionally, we detected upregulation of autophagy genes, and downregulation of the genes involved in ribosomal and mitochondrial function leading to defective oxidative phosphorylation. The upregulation of the genes associated with inflammation, apoptosis and muscle regeneration was observed only in vacuolated fibers. Notably, enzyme replacement therapy - the only available therapy for the disease - showed a tendency to restore metabolism dysregulation, particularly within slow fibers. A combination of single nuclei RNA sequencing and spatial transcriptomics revealed the landscape of normal and the diseased muscle, and highlighted the early abnormalities associated with the disease progression. Thus, the application of these two new cutting-edge technologies provided insight into the molecular pathophysiology of muscle damage in LOPD and identified potential avenues for therapeutic intervention., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain.)
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- 2024
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7. Unraveling the molecular architecture of autoimmune thyroid diseases at spatial resolution.
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Martínez-Hernández R, Sánchez de la Blanca N, Sacristán-Gómez P, Serrano-Somavilla A, Muñoz De Nova JL, Sánchez Cabo F, Heyn H, Sampedro-Núñez M, and Marazuela M
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- Humans, Fibroblasts metabolism, Fibroblasts pathology, Histocompatibility Antigens Class II metabolism, Histocompatibility Antigens Class II genetics, Thyroid Epithelial Cells metabolism, Thyroid Epithelial Cells pathology, Endothelial Cells metabolism, Endothelial Cells pathology, Transcriptome, Myofibroblasts metabolism, Myofibroblasts pathology, Stromal Cells metabolism, Stromal Cells pathology, Female, Macrophage Migration-Inhibitory Factors, Intramolecular Oxidoreductases, Graves Disease pathology, Graves Disease immunology, Graves Disease genetics, Graves Disease metabolism, Thyroid Gland pathology, Thyroid Gland metabolism, Hashimoto Disease pathology, Hashimoto Disease immunology, Hashimoto Disease metabolism, Hashimoto Disease genetics, Antigens, Differentiation, B-Lymphocyte metabolism, Antigens, Differentiation, B-Lymphocyte genetics
- Abstract
Autoimmune thyroid diseases (AITD) such as Graves' disease (GD) or Hashimoto's thyroiditis (HT) are organ-specific diseases that involve complex interactions between distinct components of thyroid tissue. Here, we use spatial transcriptomics to explore the molecular architecture, heterogeneity and location of different cells present in the thyroid tissue, including thyroid follicular cells (TFCs), stromal cells such as fibroblasts, endothelial cells, and thyroid infiltrating lymphocytes. We identify damaged antigen-presenting TFCs with upregulated CD74 and MIF expression in thyroid samples from AITD patients. Furthermore, we discern two main fibroblast subpopulations in the connective tissue including ADIRF
+ myofibroblasts, mainly enriched in GD, and inflammatory fibroblasts, enriched in HT patients. We also demonstrate an increase of fenestrated PLVAP+ vessels in AITD, especially in GD. Our data unveil stromal and thyroid epithelial cell subpopulations that could play a role in the pathogenesis of AITD., (© 2024. The Author(s).)- Published
- 2024
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8. Systematic benchmarking of single-cell ATAC-sequencing protocols.
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De Rop FV, Hulselmans G, Flerin C, Soler-Vila P, Rafels A, Christiaens V, González-Blas CB, Marchese D, Caratù G, Poovathingal S, Rozenblatt-Rosen O, Slyper M, Luo W, Muus C, Duarte F, Shrestha R, Bagdatli ST, Corces MR, Mamanova L, Knights A, Meyer KB, Mulqueen R, Taherinasab A, Maschmeyer P, Pezoldt J, Lambert CLG, Iglesias M, Najle SR, Dossani ZY, Martelotto LG, Burkett Z, Lebofsky R, Martin-Subero JI, Pillai S, Sebé-Pedrós A, Deplancke B, Teichmann SA, Ludwig LS, Braun TP, Adey AC, Greenleaf WJ, Buenrostro JD, Regev A, Aerts S, and Heyn H
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- Humans, Chromatin Immunoprecipitation Sequencing methods, Chromatin genetics, Transposases genetics, Sequence Analysis, DNA methods, High-Throughput Nucleotide Sequencing methods, Single-Cell Analysis methods, Benchmarking, Leukocytes, Mononuclear
- Abstract
Single-cell assay for transposase-accessible chromatin by sequencing (scATAC-seq) has emerged as a powerful tool for dissecting regulatory landscapes and cellular heterogeneity. However, an exploration of systemic biases among scATAC-seq technologies has remained absent. In this study, we benchmark the performance of eight scATAC-seq methods across 47 experiments using human peripheral blood mononuclear cells (PBMCs) as a reference sample and develop PUMATAC, a universal preprocessing pipeline, to handle the various sequencing data formats. Our analyses reveal significant differences in sequencing library complexity and tagmentation specificity, which impact cell-type annotation, genotype demultiplexing, peak calling, differential region accessibility and transcription factor motif enrichment. Our findings underscore the importance of sample extraction, method selection, data processing and total cost of experiments, offering valuable guidance for future research. Finally, our data and analysis pipeline encompasses 169,000 PBMC scATAC-seq profiles and a best practices code repository for scATAC-seq data analysis, which are freely available to extend this benchmarking effort to future protocols., (© 2023. The Author(s).)
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- 2024
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9. FixNCut: single-cell genomics through reversible tissue fixation and dissociation.
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Jiménez-Gracia L, Marchese D, Nieto JC, Caratù G, Melón-Ardanaz E, Gudiño V, Roth S, Wise K, Ryan NK, Jensen KB, Hernando-Momblona X, Bernardes JP, Tran F, Sievers LK, Schreiber S, van den Berge M, Kole T, van der Velde PL, Nawijn MC, Rosenstiel P, Batlle E, Butler LM, Parish IA, Plummer J, Gut I, Salas A, Heyn H, and Martelotto LG
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- Humans, Animals, Mice, Tissue Fixation methods, Reproducibility of Results, Sequence Analysis, RNA methods, Single-Cell Analysis methods, RNA genetics, Genomics methods
- Abstract
The use of single-cell technologies for clinical applications requires disconnecting sampling from downstream processing steps. Early sample preservation can further increase robustness and reproducibility by avoiding artifacts introduced during specimen handling. We present FixNCut, a methodology for the reversible fixation of tissue followed by dissociation that overcomes current limitations. We applied FixNCut to human and mouse tissues to demonstrate the preservation of RNA integrity, sequencing library complexity, and cellular composition, while diminishing stress-related artifacts. Besides single-cell RNA sequencing, FixNCut is compatible with multiple single-cell and spatial technologies, making it a versatile tool for robust and flexible study designs., (© 2024. Crown.)
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- 2024
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10. scDrugPrio: a framework for the analysis of single-cell transcriptomics to address multiple problems in precision medicine in immune-mediated inflammatory diseases.
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Schäfer S, Smelik M, Sysoev O, Zhao Y, Eklund D, Lilja S, Gustafsson M, Heyn H, Julia A, Kovács IA, Loscalzo J, Marsal S, Zhang H, Li X, Gawel D, Wang H, and Benson M
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- Humans, Precision Medicine, Tumor Necrosis Factor Inhibitors, Gene Expression Profiling, Immunomodulating Agents, Single-Cell Analysis, Sequence Analysis, RNA, Crohn Disease, Arthritis
- Abstract
Background: Ineffective drug treatment is a major problem for many patients with immune-mediated inflammatory diseases (IMIDs). Important reasons are the lack of systematic solutions for drug prioritisation and repurposing based on characterisation of the complex and heterogeneous cellular and molecular changes in IMIDs., Methods: Here, we propose a computational framework, scDrugPrio, which constructs network models of inflammatory disease based on single-cell RNA sequencing (scRNA-seq) data. scDrugPrio constructs detailed network models of inflammatory diseases that integrate information on cell type-specific expression changes, altered cellular crosstalk and pharmacological properties for the selection and ranking of thousands of drugs., Results: scDrugPrio was developed using a mouse model of antigen-induced arthritis and validated by improved precision/recall for approved drugs, as well as extensive in vitro, in vivo, and in silico studies of drugs that were predicted, but not approved, for the studied diseases. Next, scDrugPrio was applied to multiple sclerosis, Crohn's disease, and psoriatic arthritis, further supporting scDrugPrio through prioritisation of relevant and approved drugs. However, in contrast to the mouse model of arthritis, great interindividual cellular and gene expression differences were found in patients with the same diagnosis. Such differences could explain why some patients did or did not respond to treatment. This explanation was supported by the application of scDrugPrio to scRNA-seq data from eleven individual Crohn's disease patients. The analysis showed great variations in drug predictions between patients, for example, assigning a high rank to anti-TNF treatment in a responder and a low rank in a nonresponder to that treatment., Conclusions: We propose a computational framework, scDrugPrio, for drug prioritisation based on scRNA-seq of IMID disease. Application to individual patients indicates scDrugPrio's potential for personalised network-based drug screening on cellulome-, genome-, and drugome-wide scales. For this purpose, we made scDrugPrio into an easy-to-use R package ( https://github.com/SDTC-CPMed/scDrugPrio )., (© 2024. The Author(s).)
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- 2024
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11. Integrative single-cell expression and functional studies unravels a sensitization to cytarabine-based chemotherapy through HIF pathway inhibition in AML leukemia stem cells.
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Velasco-Hernandez T, Trincado JL, Vinyoles M, Closa A, Martínez-Moreno A, Gutiérrez-Agüera F, Molina O, Rodríguez-Cortez VC, Ximeno-Parpal P, Fernández-Fuentes N, Petazzi P, Beneyto-Calabuig S, Velten L, Romecin P, Casquero R, Abollo-Jiménez F, de la Guardia RD, Lorden P, Bataller A, Lapillonne H, Stam RW, Vives S, Torrebadell M, Fuster JL, Bueno C, Sarry JE, Eyras E, Heyn H, and Menéndez P
- Abstract
Relapse remains a major challenge in the clinical management of acute myeloid leukemia (AML) and is driven by rare therapy-resistant leukemia stem cells (LSCs) that reside in specific bone marrow niches. Hypoxia signaling maintains cells in a quiescent and metabolically relaxed state, desensitizing them to chemotherapy. This suggests the hypothesis that hypoxia contributes to the chemoresistance of AML-LSCs and may represent a therapeutic target to sensitize AML-LSCs to chemotherapy. Here, we identify HIF
high and HIFlow specific AML subgroups (inv(16)/ t (8;21) and MLLr, respectively) and provide a comprehensive single-cell expression atlas of 119,000 AML cells and AML-LSCs in paired diagnostic-relapse samples from these molecular subgroups. The HIF/hypoxia pathway signature is attenuated in AML-LSCs compared with more differentiated AML cells but is more expressed than in healthy hematopoietic cells. Importantly, chemical inhibition of HIF cooperates with standard-of-care chemotherapy to impair AML growth and to substantially eliminate AML-LSCs in vitro and in vivo. These findings support the HIF pathway in the stem cell-driven drug resistance of AML and unravel avenues for combinatorial targeted and chemotherapy-based approaches to specifically eliminate AML-LSCs., Competing Interests: Pablo Menéndez is the founder of the spin‐off OneChain Immunotherapeutics, which has no connection with the present research. The other authors declare no conflict of interest., (© 2024 The Authors. HemaSphere published by John Wiley & Sons Ltd. on behalf of European Hematology Association.)- Published
- 2024
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12. Converging and evolving immuno-genomic routes toward immune escape in breast cancer.
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Blanco-Heredia J, Souza CA, Trincado JL, Gonzalez-Cao M, Gonçalves-Ribeiro S, Gil SR, Pravdyvets D, Cedeño S, Callari M, Marra A, Gazzo AM, Weigelt B, Pareja F, Vougiouklakis T, Jungbluth AA, Rosell R, Brander C, Tresserra F, Reis-Filho JS, Tiezzi DG, de la Iglesia N, Heyn H, and De Mattos-Arruda L
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- Humans, Female, Genomics methods, Tumor Microenvironment, Breast Neoplasms genetics, Triple Negative Breast Neoplasms genetics, Triple Negative Breast Neoplasms pathology
- Abstract
The interactions between tumor and immune cells along the course of breast cancer progression remain largely unknown. Here, we extensively characterize multiple sequential and parallel multiregion tumor and blood specimens of an index patient and a cohort of metastatic triple-negative breast cancers. We demonstrate that a continuous increase in tumor genomic heterogeneity and distinct molecular clocks correlated with resistance to treatment, eventually allowing tumors to escape from immune control. TCR repertoire loses diversity over time, leading to convergent evolution as breast cancer progresses. Although mixed populations of effector memory and cytotoxic single T cells coexist in the peripheral blood, defects in the antigen presentation machinery coupled with subdued T cell recruitment into metastases are observed, indicating a potent immune avoidance microenvironment not compatible with an effective antitumor response in lethal metastatic disease. Our results demonstrate that the immune responses against cancer are not static, but rather follow dynamic processes that match cancer genomic progression, illustrating the complex nature of tumor and immune cell interactions., (© 2024. The Author(s).)
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- 2024
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13. An atlas of cells in the human tonsil.
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Massoni-Badosa R, Aguilar-Fernández S, Nieto JC, Soler-Vila P, Elosua-Bayes M, Marchese D, Kulis M, Vilas-Zornoza A, Bühler MM, Rashmi S, Alsinet C, Caratù G, Moutinho C, Ruiz S, Lorden P, Lunazzi G, Colomer D, Frigola G, Blevins W, Romero-Rivero L, Jiménez-Martínez V, Vidal A, Mateos-Jaimez J, Maiques-Diaz A, Ovejero S, Moreaux J, Palomino S, Gomez-Cabrero D, Agirre X, Weniger MA, King HW, Garner LC, Marini F, Cervera-Paz FJ, Baptista PM, Vilaseca I, Rosales C, Ruiz-Gaspà S, Talks B, Sidhpura K, Pascual-Reguant A, Hauser AE, Haniffa M, Prosper F, Küppers R, Gut IG, Campo E, Martin-Subero JI, and Heyn H
- Subjects
- Humans, Adult, Palatine Tonsil, B-Lymphocytes metabolism
- Abstract
Palatine tonsils are secondary lymphoid organs (SLOs) representing the first line of immunological defense against inhaled or ingested pathogens. We generated an atlas of the human tonsil composed of >556,000 cells profiled across five different data modalities, including single-cell transcriptome, epigenome, proteome, and immune repertoire sequencing, as well as spatial transcriptomics. This census identified 121 cell types and states, defined developmental trajectories, and enabled an understanding of the functional units of the tonsil. Exemplarily, we stratified myeloid slan-like subtypes, established a BCL6 enhancer as locally active in follicle-associated T and B cells, and identified SIX5 as putative transcriptional regulator of plasma cell maturation. Analyses of a validation cohort confirmed the presence, annotation, and markers of tonsillar cell types and provided evidence of age-related compositional shifts. We demonstrate the value of this resource by annotating cells from B cell-derived mantle cell lymphomas, linking transcriptional heterogeneity to normal B cell differentiation states of the human tonsil., Competing Interests: Declaration of interests H.H. is co-founder of Omniscope, SAB member of Nanostring and MiRXES, and consultant to Moderna and Singularity. J.C.N. is consultant to Omniscope., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
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- 2024
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14. The cellular landscape of the endochondral bone during the transition to extrauterine life.
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Rueda AD, Salvador-Martínez I, Sospedra-Arrufat I, Alcaina-Caro A, Fernández-Miñán A, Burgos-Ruiz AM, Cases I, Mohedano A, Tena JJ, Heyn H, Lopez-Rios J, and Nusspaumer G
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- Mice, Animals, Bone and Bones, Bone Marrow, Hematopoiesis, Osteogenesis genetics, Mesenchymal Stem Cells
- Abstract
The cellular complexity of the endochondral bone underlies its essential and pleiotropic roles during organismal life. While the adult bone has received significant attention, we still lack a deep understanding of the perinatal bone cellulome. Here, we have profiled the full composition of the murine endochondral bone at the single-cell level during the transition from fetal to newborn life and in comparison with the adult tissue, with particular emphasis on the mesenchymal compartment. The perinatal bone contains different fibroblastic clusters with blastema-like characteristics in organizing and supporting skeletogenesis, angiogenesis and hematopoiesis. Our data also suggest dynamic inter- and intra-compartment interactions, as well as a bone marrow milieu that seems prone to anti-inflammation, which we hypothesize is necessary to ensure the proper program of lymphopoiesis and the establishment of central and peripheral tolerance in early life. Our study provides an integrative roadmap for the future design of genetic and cellular functional assays to validate cellular interactions and lineage relationships within the perinatal bone., (© 2024 The Authors. Immunology & Cell Biology published by John Wiley & Sons Australia, Ltd on behalf of the Australian and New Zealand Society for Immunology, Inc.)
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- 2024
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15. Author Correction: Macrophage and neutrophil heterogeneity at single-cell spatial resolution in human inflammatory bowel disease.
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Garrido-Trigo A, Corraliza AM, Veny M, Dotti I, Melón-Ardanaz E, Rill A, Crowell HL, Corbí Á, Gudiño V, Esteller M, Álvarez-Teubel I, Aguilar D, Masamunt MC, Killingbeck E, Kim Y, Leon M, Visvanathan S, Marchese D, Caratù G, Martin-Cardona A, Esteve M, Ordás I, Panés J, Ricart E, Mereu E, Heyn H, and Salas A
- Published
- 2024
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16. Single-cell multi-omics analysis of COVID-19 patients with pre-existing autoimmune diseases shows aberrant immune responses to infection.
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Barmada A, Handfield LF, Godoy-Tena G, de la Calle-Fabregat C, Ciudad L, Arutyunyan A, Andrés-León E, Hoo R, Porter T, Oszlanczi A, Richardson L, Calero-Nieto FJ, Wilson NK, Marchese D, Sancho-Serra C, Carrillo J, Presas-Rodríguez S, Ramo-Tello C, Ruiz-Sanmartin A, Ferrer R, Ruiz-Rodriguez JC, Martínez-Gallo M, Munera-Campos M, Carrascosa JM, Göttgens B, Heyn H, Prigmore E, Casafont-Solé I, Solanich X, Sánchez-Cerrillo I, González-Álvaro I, Raimondo MG, Ramming A, Martin J, Martínez-Cáceres E, Ballestar E, Vento-Tormo R, and Rodríguez-Ubreva J
- Subjects
- Humans, SARS-CoV-2, Leukocytes, Mononuclear, Multiomics, Autoimmunity, Single-Cell Analysis, COVID-19, Autoimmune Diseases
- Abstract
In COVID-19, hyperinflammatory and dysregulated immune responses contribute to severity. Patients with pre-existing autoimmune conditions can therefore be at increased risk of severe COVID-19 and/or associated sequelae, yet SARS-CoV-2 infection in this group has been little studied. Here, we performed single-cell analysis of peripheral blood mononuclear cells from patients with three major autoimmune diseases (rheumatoid arthritis, psoriasis, or multiple sclerosis) during SARS-CoV-2 infection. We observed compositional differences between the autoimmune disease groups coupled with altered patterns of gene expression, transcription factor activity, and cell-cell communication that substantially shape the immune response under SARS-CoV-2 infection. While enrichment of HLA-DRlow CD14+ monocytes was observed in all three autoimmune disease groups, type-I interferon signaling as well as inflammatory T cell and monocyte responses varied widely between the three groups of patients. Our results reveal disturbed immune responses to SARS-CoV-2 in patients with pre-existing autoimmunity, highlighting important considerations for disease treatment and follow-up., (© 2023 The Authors. European Journal of Immunology published by Wiley-VCH GmbH.)
- Published
- 2024
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