Maristella Steri

@article{pmid33216977,

title = {A Sardinian founder mutation in glycoprotein Ib platelet subunit beta(GP1BB) that impacts thrombocytopenia},

author = { F. Busonero and M. Steri and V. Orrù and G. Sole and S. Olla and M. Marongiu and A. Maschio and C. Sidore and S. Lai and A. Mulas and M. Zoledziewska and M. Floris and M. Pala and P. Forabosco and I. Asunis and M. Pitzalis and F. Deidda and M. Masala and C. A. Caria and S. Barella and G. R. Abecasis and D. Schlessinger and S. Sanna and E. Fiorillo and F. Cucca},

year  = {2020},

date = {2020-11-01},

journal = {Br J Haematol},

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},

year  = {2020},

date = {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{danjou_genome-wide_2015,

title = {Genome-wide association analyses based on whole-genome sequencing in Sardinia provide insights into regulation of hemoglobin levels},

author = {Fabrice Danjou and Magdalena Zoledziewska and Carlo Sidore and Maristella Steri and Fabio Busonero and Andrea Maschio and Antonella Mulas and Lucia Perseu and Susanna Barella and Eleonora Porcu and Giorgio Pistis and Maristella Pitzalis and Mauro Pala and Stephan Menzel and Sarah Metrustry and Timothy D Spector and Lidia Leoni and Andrea Angius and Manuela Uda and Paolo Moi and Swee Lay Thein and Renzo Galanello and Gon{ç}alo R Abecasis and David Schlessinger and Serena Sanna and Francesco Cucca},

doi = {10.1038/ng.3307},

issn = {1546-1718},

year  = {2015},

date = {2015-11-01},

journal = {Nature Genetics},

volume = {47},

number = {11},

pages = {1264--1271},

abstract = {We report genome-wide association study results for the levels of A1, A2 and fetal hemoglobins, analyzed for the first time concurrently. Integrating high-density array genotyping and whole-genome sequencing in a large general population cohort from Sardinia, we detected 23 associations at 10 loci. Five signals are due to variants at previously undetected loci: MPHOSPH9, PLTP-PCIF1, ZFPM1 (FOG1), NFIX and CCND3. Among the signals at known loci, ten are new lead variants and four are new independent signals. Half of all variants also showed pleiotropic associations with different hemoglobins, which further corroborated some of the detected associations and identified features of coordinated hemoglobin species production.},

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}

}