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21 results on '"Marongiu, Michele"'

6. The longitudinal dynamics and natural history of clonal haematopoiesis

Author

Fabre, Margarete A., de Almeida, José Guilherme, Fiorillo, Edoardo, Mitchell, Emily, Damaskou, Aristi, Rak, Justyna, Orrù, Valeria, Marongiu, Michele, Chapman, Michael Spencer, Vijayabaskar, M. S., Baxter, Joanna, Hardy, Claire, Abascal, Federico, Williams, Nicholas, Nangalia, Jyoti, Martincorena, Iñigo, Campbell, Peter J., McKinney, Eoin F., Cucca, Francesco, Gerstung, Moritz, and Vassiliou, George S.

Published
2022
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7. The Women4Health (W4H) cohort: A unique cohort to study women-specific mechanisms of cardio-metabolic regulation

Author

Busonero, Fabio, primary, Lenarduzzi, Stefania, additional, Crobu, Francesca, additional, Gentile, Roberta Maria, additional, Carta, Andrea, additional, Cracco, Francesco, additional, Maschio, Andrea, additional, Camarda, Silvia, additional, Marongiu, Michele, additional, Zanetti, Daniela, additional, Conversano, Claudio, additional, Di Lorenzo, Giovanni, additional, Mazzà, Daniela, additional, De Seta, Francesco, additional, Girotto, Giorgia, additional, and Sanna, Serena, additional

Published
2024
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9. Implications of disease-modifying therapies for multiple sclerosis on immune cells and response to COVID-19 vaccination.

Author

Orrù, Valeria, Serra, Valentina, Marongiu, Michele, Lai, Sandra, Lodde, Valeria, Zoledziewska, Magdalena, Steri, Maristella, Loizedda, Annalisa, Lobina, Monia, Piras, Maria Grazia, Virdis, Francesca, Delogu, Giuseppe, Marini, Maria Giuseppina, Mingoia, Maura, Floris, Matteo, Masala, Marco, Castelli, M. Paola, Mostallino, Rafaela, Frau, Jessica, and Lorefice, Lorena

Subjects
COVID-19 vaccines, VACCINE effectiveness, BOOSTER vaccines, COVID-19 pandemic, DIMETHYL fumarate, NATALIZUMAB, FINGOLIMOD
Abstract

Introduction: Disease-modifying therapies (DMTs) have been shown to improve disease outcomes in multiple sclerosis (MS) patients. They may also impair the immune response to vaccines, including the SARS-CoV-2 vaccine. However, available data on both the intrinsic immune effects of DMTs and their influence on cellular response to the SARS-CoV-2 vaccine are still incomplete. Methods: Here, we evaluated the immune cell effects of 3 DMTs on the response to mRNA SARS-CoV-2 vaccination by comparing MS patients treated with one specific therapy (fingolimod, dimethyl fumarate, or natalizumab) with both healthy controls and untreated patients. We profiled 23 B-cell traits, 57 T-cell traits, and 10 cytokines, both at basal level and after stimulation with a pool of SARS-CoV-2 spike peptides, in 79 MS patients, treated with DMTs or untreated, and 32 healthy controls. Measurements were made before vaccination and at three time points after immunization. Results and Discussion: MS patients treated with fingolimod showed the strongest immune cell dysregulation characterized by a reduction in all measured lymphocyte cell classes; the patients also had increased immune cell activation at baseline, accompanied by reduced specific immune cell response to the SARS-CoV-2 vaccine. Also, anti-spike specific B cells progressively increased over the three time points after vaccination, even when antibodies measured from the same samples instead showed a decline. Our findings demonstrate that repeated booster vaccinations in MS patients are crucial to overcoming the immune cell impairment caused by DMTs and achieving an immune response to the SARS-CoV-2 vaccine comparable to that of healthy controls. [ABSTRACT FROM AUTHOR]

Published
2024
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10. Echocardiographic heart ageing patterns predict cardiovascular and non-cardiovascular events and reflect biological age: the SardiNIA study

Author

Ganau, Antonello, primary, Orr, Marco, additional, Floris, Matteo, additional, Saba, Pier Sergio, additional, Loi, Federica, additional, Sanna, Giuseppe D, additional, Marongiu, Michele, additional, Balaci, Lenuta, additional, Curreli, Niccolò, additional, Ferreli, Liana A P, additional, Loi, Francesco, additional, Masala, Marco, additional, Parodi, Guido, additional, Delitala, Alessandro P, additional, Schlessinger, David, additional, Lakatta, Edward, additional, Fiorillo, Edoardo, additional, and Cucca, Francesco, additional

Published
2023
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11. Echocardiographic heart ageing patterns predict cardiovascular and non-cardiovascular events and reflect biological age: the SardiNIA study.

Author

Ganau, Antonello, Orrù, Marco, Floris, Matteo, Saba, Pier Sergio, Loi, Federica, Sanna, Giuseppe D, Marongiu, Michele, Balaci, Lenuta, Curreli, Niccolò, Ferreli, Liana A P, Loi, Francesco, Masala, Marco, Parodi, Guido, Delitala, Alessandro P, Schlessinger, David, Lakatta, Edward, Fiorillo, Edoardo, and Cucca, Francesco

Published
2024
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12. The Women4Health cohort: a unique cohort to study women-specific mechanisms of cardio-metabolic regulation.

Author

Busonero, Fabio, Lenarduzzi, Stefania, Crobu, Francesca, Gentile, Roberta Marie, Carta, Andrea, Cracco, Francesco, Maschio, Andrea, Camarda, Silvia, Marongiu, Michele, Zanetti, Daniela, Conversano, Claudio, Di Lorenzo, Giovanni, Mazzà, Daniela, De Seta, Francesco, Girotto, Giorgia, and Sanna, Serena

Subjects
GUT microbiome, LIPID metabolism, COHORT analysis, GASTROINTESTINAL hormones, SEX hormones
Abstract

Aims: Epidemiological research has shown relevant differences between sexes in clinical manifestations, severity, and progression of cardiovascular and metabolic disorders. To date, the mechanisms underlying these differences remain unknown. Given the rising incidence of such diseases, gender-specific research on established and emerging risk factors, such as dysfunction of glycaemic and/or lipid metabolism, of sex hormones and of gut microbiome, is of paramount importance. The relationships between sex hormones, gut microbiome, and host glycaemic and/or lipid metabolism are largely unknown even in the homoeostasis status. Yet this knowledge gap would be pivotal to pinpoint to key mechanisms that are likely to be disrupted in disease context. Methods and results: Here we present the Women4Health (W4H) cohort, a unique cohort comprising up to 300 healthy women followed up during a natural menstrual cycle, set up with the primary goal to investigate the combined role of sex hormones and gut microbiota variations in regulating host lipid and glucose metabolism during homoeostasis, using a multi-omics strategy. Additionally, the W4H cohort will take into consideration another ecosystem that is unique to women, the vaginal microbiome, investigating its interaction with gut microbiome and exploring-for the first time-its role in cardiometabolic disorders. Conclusion: The W4H cohort study lays a foundation for improving current knowledge of women-specific mechanisms in cardiometabolic regulation. It aspires to transform insights on host-microbiota interactions into prevention and therapeutic approaches for personalized health care. [ABSTRACT FROM AUTHOR]

Published
2024
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13. GWAS of genetic factors affecting white blood cell morphological parameters in Sardinians uncovers influence of chromosome 11 innate immunity gene cluster on eosinophil morphology

Author

Agencia Estatal de Investigación (España), European Commission, Junta de Andalucía, Universidad de Sevilla, Fundación Ramón Areces, Marongiu, Michele, Pérez-Mejías, Gonzalo, Orrù, Valeria, Steri, Maristella, Sidore, Carlo, Díaz-Quintana, Antonio, Mulas, Antonella, Busonero, Fabio, Maschio, Andrea, Walter, Klaudia, Tardaguila, Manuel, Akbari, Parsa, Soranzo, Nicole, Fiorillo, Edoardo, Gorospe, Myriam, Schlessinger, David, Díaz-Moreno, Irene, Cucca, Francesco, Zoledziewska, Magdalena, Agencia Estatal de Investigación (España), European Commission, Junta de Andalucía, Universidad de Sevilla, Fundación Ramón Areces, Marongiu, Michele, Pérez-Mejías, Gonzalo, Orrù, Valeria, Steri, Maristella, Sidore, Carlo, Díaz-Quintana, Antonio, Mulas, Antonella, Busonero, Fabio, Maschio, Andrea, Walter, Klaudia, Tardaguila, Manuel, Akbari, Parsa, Soranzo, Nicole, Fiorillo, Edoardo, Gorospe, Myriam, Schlessinger, David, Díaz-Moreno, Irene, Cucca, Francesco, and Zoledziewska, Magdalena

Abstract

Few genome-wide association studies (GWAS) analyzing genetic regulation of morphological traits of white blood cells have been reported. We carried out a GWAS of 12 morphological traits in 869 individuals from the general population of Sardinia, Italy. These traits, included measures of cell volume, conductivity and light scatter in four white-cell populations (eosinophils, lymphocytes, monocytes, neutrophils). This analysis yielded seven statistically significant signals, four of which were novel (four novel, PRG2, P2RX3, two of CDK6). Five signals were replicated in the independent INTERVAL cohort of 11 822 individuals. The most interesting signal with large effect size on eosinophil scatter (P-value = 8.33 x 10-32, beta = -1.651, se = 0.1351) falls within the innate immunity cluster on chromosome 11, and is located in the PRG2 gene. Computational analyses revealed that a rare, Sardinian-specific PRG2:p.Ser148Pro mutation modifies PRG2 amino acid contacts and protein dynamics in a manner that could possibly explain the changes observed in eosinophil morphology. Our discoveries shed light on genetics of morphological traits. For the first time, we describe such large effect size on eosinophils morphology that is relatively frequent in Sardinian population.

Published
2023

15. Patterns of Dietary Blood Markers Are Related to Frailty Status in the FRAILOMIC Validation Phase

Author

Henning, Thorsten, primary, Kochlik, Bastian, additional, Ara, Ignacio, additional, González-Gross, Marcela, additional, Fiorillo, Edoardo, additional, Marongiu, Michele, additional, Cucca, Francesco, additional, Rodriguez-Artalejo, Fernando, additional, Carnicero Carreño, Jose Antonio, additional, Rodriguez-Mañas, Leocadio, additional, Grune, Tilman, additional, and Weber, Daniela, additional

Published
2023
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17. Polygenic risk score and biochemical/environmental variables predict a low-risk profile of age-related macular degeneration in Sardinia

Author

Serra, Rita, primary, Rallo, Vincenzo, additional, Pinna, Antonio, additional, Steri, Maristella, additional, Piras, Maria Grazia, additional, Marongiu, Michele, additional, Coscas, Florence, additional, Gorospe, Myriam, additional, Schlessinger, David, additional, Fiorillo, Edoardo, additional, Cucca, Francesco, additional, and Angius, Andrea, additional

Published
2022
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18. GWAS of genetic factors affecting white blood cell morphological parameters in Sardinians uncovers influence of chromosome 11 innate immunity gene cluster on eosinophil morphology

Author

Marongiu, Michele, primary, Pérez-Mejías, Gonzalo, additional, Orrù, Valeria, additional, Steri, Maristella, additional, Sidore, Carlo, additional, Díaz-Quintana, Antonio, additional, Mulas, Antonella, additional, Busonero, Fabio, additional, Maschio, Andrea, additional, Walter, Klaudia, additional, Tardaguila, Manuel, additional, Akbari, Parsa, additional, Soranzo, Nicole, additional, Fiorillo, Edoardo, additional, Gorospe, Myriam, additional, Schlessinger, David, additional, Díaz-Moreno, Irene, additional, Cucca, Francesco, additional, and Zoledziewska, Magdalena, additional

Published
2022
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19. Facets of Personality and Risk of Cognitive Impairment: Longitudinal Findings in a Rural Community from Sardinia

Author

Terracciano, Antonio, primary, Piras, Maria Rita, additional, Sutin, Angelina R., additional, Delitala, Alessandro, additional, Curreli, Nicolò Camillo, additional, Balaci, Lenuta, additional, Marongiu, Michele, additional, Zhu, Xianghe, additional, Aschwanden, Damaris, additional, Luchetti, Martina, additional, Oppong, Richard, additional, Schlessinger, David, additional, Cucca, Francesco, additional, Launer, Lenore J., additional, and Fiorillo, Edoardo, additional

Published
2022
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20. GWAS of genetic factors affecting white blood cell morphological parameters in Sardinians uncovers influence of chromosome 11 innate immunity gene cluster on eosinophil morphology.

Author

Marongiu, Michele, Pérez-Mejías, Gonzalo, Orrù, Valeria, Steri, Maristella, Sidore, Carlo, Díaz-Quintana, Antonio, Mulas, Antonella, Busonero, Fabio, Maschio, Andrea, Walter, Klaudia, Tardaguila, Manuel, Akbari, Parsa, Soranzo, Nicole, Fiorillo, Edoardo, Gorospe, Myriam, Schlessinger, David, Díaz-Moreno, Irene, Cucca, Francesco, and Zoledziewska, Magdalena

Published
2023
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21. The longitudinal dynamics and natural history of clonal haematopoiesis

Author

Margarete A. Fabre, José Guilherme de Almeida, Edoardo Fiorillo, Emily Mitchell, Aristi Damaskou, Justyna Rak, Valeria Orrù, Michele Marongiu, Michael Spencer Chapman, M. S. Vijayabaskar, Joanna Baxter, Claire Hardy, Federico Abascal, Nicholas Williams, Jyoti Nangalia, Iñigo Martincorena, Peter J. Campbell, Eoin F. McKinney, Francesco Cucca, Moritz Gerstung, George S. Vassiliou, Orrù, Valeria [0000-0002-6047-4625], Marongiu, Michele [0000-0002-7289-9815], Chapman, Michael Spencer [0000-0002-5320-8193], Abascal, Federico [0000-0002-6201-1587], Williams, Nicholas [0000-0003-3989-9167], Nangalia, Jyoti [0000-0001-7122-4608], Martincorena, Iñigo [0000-0003-1122-4416], Campbell, Peter J [0000-0002-3921-0510], Gerstung, Moritz [0000-0001-6709-963X], Vassiliou, George [0000-0003-4337-8022], Apollo - University of Cambridge Repository, and Vassiliou, George S [0000-0003-4337-8022]

Subjects
141, Aging, Multidisciplinary, Genome, Human, article, 692/699/67/1990/283/1897, 45/23, Middle Aged, 631/208/737, Clone Cells, 631/114/2397, 692/699/67/1990/1673, Mutation, Humans, Longitudinal Studies, 45/100, Clonal Hematopoiesis, 692/499, Phylogeny, Aged
Abstract

Funder: European Research Council, Clonal expansions driven by somatic mutations become pervasive across human tissues with age, including in the haematopoietic system, where the phenomenon is termed clonal haematopoiesis1-4. The understanding of how and when clonal haematopoiesis develops, the factors that govern its behaviour, how it interacts with ageing and how these variables relate to malignant progression remains limited5,6. Here we track 697 clonal haematopoiesis clones from 385 individuals 55 years of age or older over a median of 13 years. We find that 92.4% of clones expanded at a stable exponential rate over the study period, with different mutations driving substantially different growth rates, ranging from 5% (DNMT3A and TP53) to more than 50% per year (SRSF2P95H). Growth rates of clones with the same mutation differed by approximately ±5% per year, proportionately affecting slow drivers more substantially. By combining our time-series data with phylogenetic analysis of 1,731 whole-genome sequences of haematopoietic colonies from 7 individuals from an older age group, we reveal distinct patterns of lifelong clonal behaviour. DNMT3A-mutant clones preferentially expanded early in life and displayed slower growth in old age, in the context of an increasingly competitive oligoclonal landscape. By contrast, splicing gene mutations drove expansion only later in life, whereas TET2-mutant clones emerged across all ages. Finally, we show that mutations driving faster clonal growth carry a higher risk of malignant progression. Our findings characterize the lifelong natural history of clonal haematopoiesis and give fundamental insights into the interactions between somatic mutation, ageing and clonal selection.

Published
2022

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