Monia Lobina

@article{Piperni2024-ph,

title = {Intestinal Blastocystis is linked to healthier diets and more  favorable cardiometabolic outcomes in 56,989 individuals from 32  countries},

author = {Elisa Piperni and Long H Nguyen and Paolo Manghi and Hanseul Kim and Edoardo Pasolli and Sergio Andreu-Sánchez and Alberto Arr`e and Kate M Bermingham and Aitor Blanco-M'iguez and Serena Manara and Mireia Valles-Colomer and Elco Bakker and Fabio Busonero and Richard Davies and Edoardo Fiorillo and Francesca Giordano and George Hadjigeorgiou and Emily R Leeming and Monia Lobina and Marco Masala and Andrea Maschio and Lauren J McIver and Mauro Pala and Maristella Pitzalis and Jonathan Wolf and Jingyuan Fu and Alexandra Zhernakova and Simone M Cacci`o and Francesco Cucca and Sarah E Berry and Danilo Ercolini and Andrew T Chan and Curtis Huttenhower and Tim D Spector and Nicola Segata and Francesco Asnicar},

doi = {10.1016/j.cell.2024.06.018},

year  = {2024},

date = {2024-08-01},

urldate = {2024-08-01},

journal = {Cell},

volume = {187},

number = {17},

pages = {4554--4570.e18},

publisher = {Elsevier BV},

abstract = {Diet impacts human health, influencing body adiposity and the 

 risk of developing cardiometabolic diseases. The gut microbiome 

 is a key player in the diet-health axis, but while its bacterial 

 fraction is widely studied, the role of micro-eukaryotes, 

 including Blastocystis, is underexplored. We performed a 

 global-scale analysis on 56,989 metagenomes and showed that 

 human Blastocystis exhibits distinct prevalence patterns linked 

 to geography, lifestyle, and dietary habits. Blastocystis 

 presence defined a specific bacterial signature and was 

 positively associated with more favorable cardiometabolic 

 profiles and negatively with obesity (p < 1e-16) and disorders 

 linked to altered gut ecology (p < 1e-8). In a diet intervention 

 study involving 1,124 individuals, improvements in dietary 

 quality were linked to weight loss and increases in Blastocystis prevalence (p = 0.003) and abundance (p < 1e-7). Our findings 

 suggest a potentially beneficial role for Blastocystis, which 

 may help explain personalized host responses to diet and 

 downstream disease etiopathogenesis.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Orru2024-hd,

title = {Implications of disease-modifying therapies for multiple  sclerosis on immune cells and response to COVID-19 vaccination},

author = {Valeria Örr`u and Valentina Serra and Michele Marongiu and Sandra Lai and Valeria Lodde and Magdalena Zoledziewska and Maristella Steri and Annalisa Loizedda and Monia Lobina and Maria Grazia Piras and Francesca Virdis and Giuseppe Delogu and Maria Giuseppina Marini and Maura Mingoia and Matteo Floris and Marco Masala and M Paola Castelli and Rafaela Mostallino and Jessica Frau and Lorena Lorefice and Gabriele Farina and Marzia Fronza and Daniele Carmagnini and Elisa Carta and Silvy Pilotto and Paola Chessa and Marcella Devoto and Paolo Castiglia and Paolo Solla and Roberto Ignazio Zarbo and Maria Laura Idda and Maristella Pitzalis and Eleonora Cocco and Edoardo Fiorillo and Francesco" Cucca},

doi = {10.3389/fimmu.2024.1416464},

year  = {2024},

date = {2024-07-01},

urldate = {2024-07-01},

journal = {Front. Immunol.},

volume = {15},

pages = {1416464},

publisher = {Frontiers Media SA},

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.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid32929287,

title = {Complex genetic signatures in immune cells underlie autoimmunity and inform therapy},

author = {V Orrù and M Steri and C Sidore and M Marongiu and V Serra and S Olla and G Sole and S Lai and M Dei and A Mulas and F Virdis and MG Piras and M Lobina and M Marongiu and M Pitzalis and F Deidda and A Loizedda and S Onano and M Zoledziewska and S Sawcer and M Devoto and M Gorospe and GR Abecasis and M Floris and M Pala and D Schlessinger and E Fiorillo and F Cucca},

doi = {10.1038/s41588-020-0684-4},

year  = {2020},

date = {2020-01-01},

urldate = {2020-01-01},

journal = {Nat Genet},

volume = {52},

number = {10},

pages = {1036--1045},

abstract = {We report on the influence of ~22 million variants on 731 immune cell traits in a cohort of 3,757 Sardinians. We detected 122 significant (P < 1.28 × 10-11) independent association signals for 459 cell traits at 70 loci (53 of them novel) identifying several molecules and mechanisms involved in cell regulation. Furthermore, 53 signals at 36 loci overlapped with previously reported disease-associated signals, predominantly for autoimmune disorders, highlighting intermediate phenotypes in pathogenesis. Collectively, our findings illustrate complex genetic regulation of immune cells with highly selective effects on autoimmune disease risk at the cell-subtype level. These results identify drug-targetable pathways informing the design of more specific treatments for autoimmune diseases.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{steri_overexpression_2017,

title = {Overexpression of the Cytokine BAFF and Autoimmunity Risk},

author = {Maristella Steri and Valeria Orrù and Laura M Idda and Maristella Pitzalis and Mauro Pala and Ilenia Zara and Carlo Sidore and Valeria Faà and Matteo Floris and Manila Deiana and Isadora Asunis and Eleonora Porcu and Antonella Mulas and Maria G Piras and Monia Lobina and Sandra Lai and Mara Marongiu and Valentina Serra and Michele Marongiu and Gabriella Sole and Fabio Busonero and Andrea Maschio and Roberto Cusano and Gianmauro Cuccuru and Francesca Deidda and Fausto Poddie and Gabriele Farina and Mariano Dei and Francesca Virdis and Stefania Olla and Maria A Satta and Mario Pani and Alessandro Delitala and Eleonora Cocco and Jessica Frau and Giancarlo Coghe and Lorena Lorefice and Giuseppe Fenu and Paola Ferrigno and Maria Ban and Nadia Barizzone and Maurizio Leone and Franca R Guerini and Matteo Piga and Davide Firinu and Ingrid Kockum and Izaura {Lima Bomfim} and Tomas Olsson and Lars Alfredsson and Ana Suarez and Patricia E Carreira and Maria J Castillo-Palma and Joseph H Marcus and Mauro Congia and Andrea Angius and Maurizio Melis and Antonio Gonzalez and Marta E {Alarc{ó}n Riquelme} and Berta M da Silva and Maurizio Marchini and Maria G Danieli and Stefano {Del Giacco} and Alessandro Mathieu and Antonello Pani and Stephen B Montgomery and Giulio Rosati and Jan Hillert and Stephen Sawcer and Sandra D'Alfonso and John A Todd and John Novembre and Gon{ç}alo R Abecasis and Michael B Whalen and Maria G Marrosu and Alessandra Meloni and Serena Sanna and Myriam Gorospe and David Schlessinger and Edoardo Fiorillo and Magdalena Zoledziewska and Francesco Cucca},

doi = {10.1056/NEJMoa1610528},

issn = {1533-4406},

year  = {2017},

date = {2017-01-01},

journal = {The New England Journal of Medicine},

volume = {376},

number = {17},

pages = {1615--1626},

abstract = {BACKGROUND: Genomewide association studies of autoimmune diseases have mapped hundreds of susceptibility regions in the genome. However, only for a few association signals has the causal gene been identified, and for even fewer have the causal variant and underlying mechanism been defined. Coincident associations of DNA variants affecting both the risk of autoimmune disease and quantitative immune variables provide an informative route to explore disease mechanisms and drug-targetable pathways. 

METHODS: Using case-control samples from Sardinia, Italy, we performed a genomewide association study in multiple sclerosis followed by TNFSF13B locus-specific association testing in systemic lupus erythematosus (SLE). Extensive phenotyping of quantitative immune variables, sequence-based fine mapping, cross-population and cross-phenotype analyses, and gene-expression studies were used to identify the causal variant and elucidate its mechanism of action. Signatures of positive selection were also investigated. 

RESULTS: A variant in TNFSF13B, encoding the cytokine and drug target B-cell activating factor (BAFF), was associated with multiple sclerosis as well as SLE. The disease-risk allele was also associated with up-regulated humoral immunity through increased levels of soluble BAFF, B lymphocytes, and immunoglobulins. The causal variant was identified: an insertion-deletion variant, GCTGT→A (in which A is the risk allele), yielded a shorter transcript that escaped microRNA inhibition and increased production of soluble BAFF, which in turn up-regulated humoral immunity. Population genetic signatures indicated that this autoimmunity variant has been evolutionarily advantageous, most likely by augmenting resistance to malaria. 

CONCLUSIONS: A TNFSF13B variant was associated with multiple sclerosis and SLE, and its effects were clarified at the population, cellular, and molecular levels. (Funded by the Italian Foundation for Multiple Sclerosis and others.).},

note = {See Editorials, Korn T, Oukka M. A BAFFling Association between Malaria Resistance and the Risk of Multiple Sclerosis. N Engl J Med. 2017 Apr 27;376(17):1680-1681. doi: 10.1056/NEJMe1700720.; Stohl W., Systemic lupus erythematosus: BAFF emerges from the genetic shadows. Nat Rev Rheumatol. 2017 Jun 15. doi: 10.1038/nrrheum.2017.99; Comabella M. Neuroimmunology: B cells and variant BAFF in autoimmune disease. Nat Rev Neurol. 2017 Jun 16. doi: 10.1038/nrneurol.2017.87.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{orru_genetic_2013,

title = {Genetic variants regulating immune cell levels in health and disease.},

author = {Valeria Orrù and Maristella Steri and Gabriella Sole and Carlo Sidore and Francesca Virdis and Mariano Dei and Sandra Lai and Magdalena Zoledziewska and Fabio Busonero and Antonella Mulas and Matteo Floris and Wieslawa I Mentzen and Silvana A M Urru and Stefania Olla and Michele Marongiu and Maria G Piras and Monia Lobina and Andrea Maschio and Maristella Pitzalis and Maria F Urru and Marco Marcelli and Roberto Cusano and Francesca Deidda and Valentina Serra and Manuela Oppo and Rosella Pilu and Frederic Reinier and Riccardo Berutti and Luca Pireddu and Ilenia Zara and Eleonora Porcu and Alan Kwong and Christine Brennan and Brendan Tarrier and Robert Lyons and Hyun M Kang and Sergio Uzzau and Rossano Atzeni and Maria Valentini and Davide Firinu and Lidia Leoni and Gianluca Rotta and Silvia Naitza and Andrea Angius and Mauro Congia and Michael B Whalen and Chris M Jones and David Schlessinger and Gon{ç}alo R Abecasis and Edoardo Fiorillo and Serena Sanna and Francesco Cucca},

doi = {10.1016/j.cell.2013.08.041},

issn = {1097-4172},

year  = {2013},

date = {2013-09-01},

journal = {Cell},

volume = {155},

number = {1},

pages = {242--56},

abstract = {The complex network of specialized cells and molecules in the immune system has evolved to defend against pathogens, but inadvertent immune system attacks on "self" result in autoimmune disease. Both genetic regulation of immune cell levels and their relationships with autoimmunity are largely undetermined. Here, we report genetic contributions to quantitative levels of 95 cell types encompassing 272 immune traits, in a cohort of 1,629 individuals from four clustered Sardinian villages. We first estimated trait heritability, showing that it can be substantial, accounting for up to 87% of the variance (mean 41%). Next, by assessing ∼8.2 million variants that we identified and confirmed in an extended set of 2,870 individuals, 23 independent variants at 13 loci associated with at least one trait. Notably, variants at three loci (HLA, IL2RA, and SH2B3/ATXN2) overlap with known autoimmune disease associations. These results connect specific cellular phenotypes to specific genetic variants, helping to explicate their involvement in disease.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}