Publications

@article{pmid36387187,

title = {Mass cytometry analysis reveals attrition of naïve and anergized self-reactive non-malignant B cells in chronic lymphocytic leukemia patients},

author = {Thibault Andrieu and Paul Mondière and Pierre-Emmanuel Jouve and Sébastien Dussurgey and Victor Malassigné and Hugo Servanton and Lucille Baseggio and Frédéric Davi and Anne-Sophie Michallet and Thierry Defrance},

doi = {10.3389/fonc.2022.1020740},

issn = {2234-943X},

year  = {2022},

date = {2022-01-01},

urldate = {2022-01-01},

journal = {Front Oncol},

volume = {12},

pages = {1020740},

abstract = {Chronic Lymphocytic Leukemia (CLL) is characterized by the progressive accumulation of monoclonal mature B lymphocytes. Autoimmune complications are common in CLL occurring in up to a quarter of all patients during the course of the illness. Etiology of autoimmunity in CLL is unknown but it is widely admitted that the pathogenic auto-Abs do not originate from the tumoral clone but from the non-malignant B cell pool. This indicates that the developmental scheme of non-malignant B cells could also be perturbed in CLL patients. To address this question, we have designed a B cell-centered antibody panel and used time-of-flight mass cytometry to compare the residual non-malignant B cell pool of CLL patients with the peripheral B cell pool of age-matched healthy donors. We show that the non-malignant B cell compartment of the patients is characterized by profound attrition of naïve B cells and of a population of anergized autoreactive B cells, suggesting impaired B cell lymphopoeisis as well as perturbations of the B cell tolerance checkpoints.},

keywords = {cytometry},

pubstate = {published},

tppubtype = {article}

}

@article{pmid33626291,

title = {Humoral and cellular immunogenicity and safety following a booster dose of a tetravalent dengue vaccine 5+ years after completion of the primary series in Singapore: 2-year follow-up of a randomized phase II, placebo-controlled trial},

author = {Juliana Park and Sophia Archuleta and May-Lin Helen Oh and Lynette Pei-Chi Shek and Hao Wang and Matthew Bonaparte and Carina Frago and Alain Bouckenooghe and Frederique Jantet-Blaudez and Sarah Begue and Sophie Gimenez-Fourage and Anke Pagnon},

doi = {10.1080/21645515.2020.1861875},

issn = {2164-554X},

year  = {2021},

date = {2021-07-01},

urldate = {2021-07-01},

journal = {Hum Vaccin Immunother},

volume = {17},

number = {7},

pages = {2107--2116},

abstract = {The tetravalent dengue vaccine (CYD-TDV) is approved for use as a 3-dose series for the prevention of dengue in seropositive individuals ≥9 years. A randomized, placebo-controlled, phase II study of a booster dose of CYD-TDV in individuals who completed the 3-dose schedule >5 years previously (NCT02824198), demonstrated that a booster restored neutralizing antibody titers to post-dose 3 levels. We present additional immunogenicity assessments up to 24 months post-booster, and B- and T-cell responses in a participant subset. Participants aged 9-45 years that had received all three doses of CYD-TDV were randomized 3:1 to receive a booster dose of CYD-TDV (n = 89) or placebo (n = 29). Neutralizing antibody levels at Months 1, 6, 12, and 24 post-booster were assessed by plaque reduction neutralization test. In a subset, B-cell responses were assessed by a fluorescent immunospot assay, and T-cells analyzed by flow cytometry at Days 0, 7, 12, Months 1 and 12. We observed an increase of antibody titers Month 1 post-booster, then a gradual decline to Month 24. In the CYD-TDV booster group, an increase in plasmablasts was seen at Day 7 declining by Day 14, an increase in memory B-cells was observed at Day 28 with no persistence at Month 12. CYD-TDV booster recalled a CD8+ T-cell response, dominated by IFN-γ secretion, which decreased 12 months post-booster. This study showed a short-term increase in antibody titers and then gradual decrease following CYD-TDV booster injection >5 years after primary immunization, and the presence of memory B-cells activated following the booster, but with low persistence.},

keywords = {cytometry},

pubstate = {published},

tppubtype = {article}

}

@article{pmid33497037,

title = {Integrative Analysis Reveals a Molecular Stratification of Systemic Autoimmune Diseases},

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

doi = {10.1002/art.41610},

issn = {2326-5205},

year  = {2021},

date = {2021-06-01},

urldate = {2021-06-01},

journal = {Arthritis Rheumatol},

volume = {73},

number = {6},

pages = {1073--1085},

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.},

keywords = {cytometry},

pubstate = {published},

tppubtype = {article}

}

@article{pmid34112769,

title = {A new molecular classification to drive precision treatment strategies in primary Sjögren's syndrome},

author = {Perrine Soret and Christelle Le Dantec and Emiko Desvaux and Nathan Foulquier and Bastien Chassagnol and Sandra Hubert and Christophe Jamin and Guillermo Barturen and Guillaume Desachy and Valérie Devauchelle-Pensec and Cheïma Boudjeniba and Divi Cornec and Alain Saraux and Sandrine Jousse-Joulin and Nuria Barbarroja and Ignasi Rodríguez-Pintó and Ellen De Langhe and Lorenzo Beretta and Carlo Chizzolini and László Kovács and Torsten Witte and Eléonore Bettacchioli and Anne Buttgereit and Zuzanna Makowska and Ralf Lesche and Maria Orietta Borghi and Javier Martin and Sophie Courtade-Gaiani and Laura Xuereb and Mickaël Guedj and Philippe Moingeon and Marta E Alarcón-Riquelme and Laurence Laigle and Jacques-Olivier Pers},

doi = {10.1038/s41467-021-23472-7},

issn = {2041-1723},

year  = {2021},

date = {2021-06-01},

urldate = {2021-06-01},

journal = {Nat Commun},

volume = {12},

number = {1},

pages = {3523},

abstract = {There is currently no approved treatment for primary Sjögren's syndrome, a disease that primarily affects adult women. The difficulty in developing effective therapies is -in part- because of the heterogeneity in the clinical manifestation and pathophysiology of the disease. Finding common molecular signatures among patient subgroups could improve our understanding of disease etiology, and facilitate the development of targeted therapeutics. Here, we report, in a cross-sectional cohort, a molecular classification scheme for Sjögren's syndrome patients based on the multi-omic profiling of whole blood samples from a European cohort of over 300 patients, and a similar number of age and gender-matched healthy volunteers. Using transcriptomic, genomic, epigenetic, cytokine expression and flow cytometry data, combined with clinical parameters, we identify four groups of patients with distinct patterns of immune dysregulation. The biomarkers we identify can be used by machine learning classifiers to sort future patients into subgroups, allowing the re-evaluation of response to treatments in clinical trials.},

keywords = {cytometry},

pubstate = {published},

tppubtype = {article}

}

@article{pmid33004331,

title = {Genomic Risk Score impact on susceptibility to systemic sclerosis},

author = {Lara Bossini-Castillo and Gonzalo Villanueva-Martin and Martin Kerick and Marialbert Acosta-Herrera and Elena López-Isac and Carmen P Simeón and Norberto Ortego-Centeno and Shervin Assassi and Nicolas Hunzelmann and Armando Gabrielli and J K de Vries-Bouwstra and Yannick Allanore and Carmen Fonseca and Christopher P Denton and Timothy Rdj Radstake and Marta Eugenia Alarcón-Riquelme and Lorenzo Beretta and Maureen D Mayes and Javier Martin},

doi = {10.1136/annrheumdis-2020-218558},

issn = {1468-2060},

year  = {2021},

date = {2021-01-01},

urldate = {2021-01-01},

journal = {Ann Rheum Dis},

volume = {80},

number = {1},

pages = {118--127},

abstract = {OBJECTIVES: Genomic Risk Scores (GRS) successfully demonstrated the ability of genetics to identify those individuals at high risk for complex traits including immune-mediated inflammatory diseases (IMIDs). We aimed to test the performance of GRS in the prediction of risk for systemic sclerosis (SSc) for the first time.



METHODS: Allelic effects were obtained from the largest SSc Genome-Wide Association Study (GWAS) to date (9 095 SSc and 17 584 healthy controls with European ancestry). The best-fitting GRS was identified under the additive model in an independent cohort that comprised 400 patients with SSc and 571 controls. Additionally, GRS for clinical subtypes (limited cutaneous SSc and diffuse cutaneous SSc) and serological subtypes (anti-topoisomerase positive (ATA+) and anti-centromere positive (ACA+)) were generated. We combined the estimated GRS with demographic and immunological parameters in a multivariate generalised linear model.



RESULTS: The best-fitting SSc GRS included 33 single nucleotide polymorphisms (SNPs) and discriminated between patients with SSc and controls (area under the receiver operating characteristic (ROC) curve (AUC)=0.673). Moreover, the GRS differentiated between SSc and other IMIDs, such as rheumatoid arthritis and Sjögren's syndrome. Finally, the combination of GRS with age and immune cell counts significantly increased the performance of the model (AUC=0.787). While the SSc GRS was not able to discriminate between ATA+ and ACA+ patients (AUC<0.5), the serological subtype GRS, which was based on the allelic effects observed for the comparison between ACA+ and ATA+ patients, reached an AUC=0.693.



CONCLUSIONS: GRS was successfully implemented in SSc. The model discriminated between patients with SSc and controls or other IMIDs, confirming the potential of GRS to support early and differential diagnosis for SSc.},

keywords = {cytometry},

pubstate = {published},

tppubtype = {article}

}

@article{pmid32561607,

title = {Genome-wide whole blood transcriptome profiling in a large European cohort of systemic sclerosis patients},

author = {Lorenzo Beretta and Guillermo Barturen and Barbara Vigone and Chiara Bellocchi and Nicolas Hunzelmann and Ellen De Langhe and Ricard Cervera and Maria Gerosa and László Kovács and Rafaela Ortega Castro and Isabel Almeida and Divi Cornec and Carlo Chizzolini and Jacques-Olivier Pers and Zuzanna Makowska and Ralf Lesche and Martin Kerick and Marta Eugenia Alarcón-Riquelme and Javier Martin },

doi = {10.1136/annrheumdis-2020-217116},

issn = {1468-2060},

year  = {2020},

date = {2020-09-01},

urldate = {2020-09-01},

journal = {Ann Rheum Dis},

volume = {79},

number = {9},

pages = {1218--1226},

abstract = {OBJECTIVES: The analysis of annotated transcripts from genome-wide expression studies may help to understand the pathogenesis of complex diseases, such as systemic sclerosis (SSc). We performed a whole blood (WB) transcriptome analysis on RNA collected in the context of the European PRECISESADS project, aiming at characterising the pathways that differentiate SSc from controls and that are reproducible in geographically diverse populations.



METHODS: Samples from 162 patients and 252 controls were collected in RNA stabilisers. Cases and controls were divided into a discovery (n=79+163; Southern Europe) and validation cohort (n=83+89; Central-Western Europe). RNA sequencing was performed by an Illumina assay. Functional annotations of Reactome pathways were performed with the Functional Analysis of Individual Microarray Expression (FAIME) algorithm. In parallel, immunophenotyping of 28 circulating cell populations was performed. We tested the presence of differentially expressed genes/pathways and the correlation between absolute cell counts and RNA transcripts/FAIME scores in regression models. Results significant in both populations were considered as replicated.



RESULTS: Overall, 15 224 genes and 1277 functional pathways were available; of these, 99 and 225 were significant in both sets. Among replicated pathways, we found a deregulation in type-I interferon, Toll-like receptor cascade, tumour suppressor p53 protein function, platelet degranulation and activation. RNA transcripts or FAIME scores were jointly correlated with cell subtypes with strong geographical differences; neutrophils were the major determinant of gene expression in SSc-WB samples.



CONCLUSIONS: We discovered a set of differentially expressed genes/pathways validated in two independent sets of patients with SSc, highlighting a number of deregulated processes that have relevance for the pathogenesis of autoimmunity and SSc.},

keywords = {cytometry},

pubstate = {published},

tppubtype = {article}

}

@article{pmid32665668,

title = {Standardization procedure for flow cytometry data harmonization in prospective multicenter studies},

author = {Lucas Le Lann and Pierre-Emmanuel Jouve and Marta Alarcón-Riquelme and Christophe Jamin and Jacques-Olivier Pers},

doi = {10.1038/s41598-020-68468-3},

issn = {2045-2322},

year  = {2020},

date = {2020-07-01},

urldate = {2020-07-01},

journal = {Sci Rep},

volume = {10},

number = {1},

pages = {11567},

abstract = {One of the most challenging objective for clinical cytometry in prospective multicenter immunomonitoring trials is to compare frequencies, absolute numbers of leukocyte populations and further the mean fluorescence intensities of cell markers, especially when the data are generated from different instruments. Here, we describe an innovative standardization workflow to compare all data to carry out any large-scale, prospective multicentric flow cytometry analysis whatever the duration, the number or type of instruments required for the realization of such projects.},

keywords = {cytometry},

pubstate = {published},

tppubtype = {article}

}

@article{pmid32264937,

title = {Delayed persistence of elevated monocytic MDSC associates with deleterious outcomes in septic shock: a retrospective cohort study},

author = {Louis Waeckel and Fabienne Venet and Morgane Gossez and Céline Monard and Thomas Rimmelé and Guillaume Monneret},

doi = {10.1186/s13054-020-02857-y},

issn = {1466-609X},

year  = {2020},

date = {2020-04-01},

urldate = {2020-04-01},

journal = {Crit Care},

volume = {24},

number = {1},

pages = {132},

keywords = {cytometry},

pubstate = {published},

tppubtype = {article}

}

@article{pmid29632146,

title = {Antigen-Induced but Not Innate Memory CD8 T Cells Express NKG2D and Are Recruited to the Lung Parenchyma upon Viral Infection},

author = {Morgan Grau and Séverine Valsesia and Julien Mafille and Sophia Djebali and Martine Tomkowiak and Anne-Laure Mathieu and Daphné Laubreton and Simon de Bernard and Pierre-Emmanuel Jouve and Erwan Ventre and Laurent Buffat and Thierry Walzer and Yann Leverrier and Jacqueline Marvel},

doi = {10.4049/jimmunol.1701698},

issn = {1550-6606},

year  = {2018},

date = {2018-05-01},

urldate = {2018-05-01},

journal = {J Immunol},

volume = {200},

number = {10},

pages = {3635--3646},

abstract = {The pool of memory-phenotype CD8 T cells is composed of Ag-induced (AI) and cytokine-induced innate (IN) cells. IN cells have been described as having properties similar to those of AI memory cells. However, we found that pathogen-induced AI memory cells can be distinguished in mice from naturally generated IN memory cells by surface expression of NKG2D. Using this marker, we described the increased functionalities of AI and IN memory CD8 T cells compared with naive cells, as shown by comprehensive analysis of cytokine secretion and gene expression. However, AI differed from IN memory CD8 T cells by their capacity to migrate to the lung parenchyma upon inflammation or infection, a process dependent on their expression of ITGA1/CD49a and ITGA4/CD49d integrins.},

keywords = {cytometry},

pubstate = {published},

tppubtype = {article}

}

@article{pmid27883012,

title = {Immune signatures of protective spleen memory CD8 T cells},

author = {Lilia Brinza and Sophia Djebali and Martine Tomkowiak and Julien Mafille and Céline Loiseau and Pierre-Emmanuel Jouve and Simon de Bernard and Laurent Buffat and Bruno Lina and Michèle Ottmann and Manuel Rosa-Calatrava and Stéphane Schicklin and Nathalie Bonnefoy and Grégoire Lauvau and Morgan Grau and Mélanie Wencker and Christophe Arpin and Thierry Walzer and Yann Leverrier and Jacqueline Marvel},

doi = {10.1038/srep37651},

issn = {2045-2322},

year  = {2016},

date = {2016-11-01},

urldate = {2016-11-01},

journal = {Sci Rep},

volume = {6},

pages = {37651},

abstract = {Memory CD8 T lymphocyte populations are remarkably heterogeneous and differ in their ability to protect the host. In order to identify the whole range of qualities uniquely associated with protective memory cells we compared the gene expression signatures of two qualities of memory CD8 T cells sharing the same antigenic-specificity: protective (Influenza-induced, Flu-TM) and non-protective (peptide-induced, TIM) spleen memory CD8 T cells. Although Flu-TM and TIM express classical phenotypic memory markers and are polyfunctional, only Flu-TM protects against a lethal viral challenge. Protective memory CD8 T cells express a unique set of genes involved in migration and survival that correlate with their unique capacity to rapidly migrate within the infected lung parenchyma in response to influenza infection. We also enlighten a new set of poised genes expressed by protective cells that is strongly enriched in cytokines and chemokines such as Ccl1, Ccl9 and Gm-csf. CCL1 and GM-CSF genes are also poised in human memory CD8 T cells. These immune signatures are also induced by two other pathogens (vaccinia virus and Listeria monocytogenes). The immune signatures associated with immune protection were identified on circulating cells, i.e. those that are easily accessible for immuno-monitoring and could help predict vaccines efficacy.},

keywords = {cytometry},

pubstate = {published},

tppubtype = {article}

}

@article{pmid27069116,

title = {CD1d-restricted peripheral T cell lymphoma in mice and humans},

author = {Emmanuel Bachy and Mirjam Urb and Shilpi Chandra and Rémy Robinot and Gabriel Bricard and Simon de Bernard and Alexandra Traverse-Glehen and Sophie Gazzo and Olivier Blond and Archana Khurana and Lucile Baseggio and Tayla Heavican and Martine Ffrench and Giuliano Crispatzu and Paul Mondière and Alexandra Schrader and Morgan Taillardet and Olivier Thaunat and Nadine Martin and Stéphane Dalle and Magali Le Garff-Tavernier and Gilles Salles and Joel Lachuer and Olivier Hermine and Vahid Asnafi and Mikael Roussel and Thierry Lamy and Marco Herling and Javeed Iqbal and Laurent Buffat and Patrice N Marche and Philippe Gaulard and Mitchell Kronenberg and Thierry Defrance and Laurent Genestier},

doi = {10.1084/jem.20150794},

issn = {1540-9538},

year  = {2016},

date = {2016-05-01},

urldate = {2016-05-01},

journal = {J Exp Med},

volume = {213},

number = {5},

pages = {841--857},

abstract = {Peripheral T cell lymphomas (PTCLs) are a heterogeneous entity of neoplasms with poor prognosis, lack of effective therapies, and a largely unknown pathophysiology. Identifying the mechanism of lymphomagenesis and cell-of-origin from which PTCLs arise is crucial for the development of efficient treatment strategies. In addition to the well-described thymic lymphomas, we found that p53-deficient mice also developed mature PTCLs that did not originate from conventional T cells but from CD1d-restricted NKT cells. PTCLs showed phenotypic features of activated NKT cells, such as PD-1 up-regulation and loss of NK1.1 expression. Injections of heat-killed Streptococcus pneumonia, known to express glycolipid antigens activating NKT cells, increased the incidence of these PTCLs, whereas Escherichia coli injection did not. Gene expression profile analyses indicated a significant down-regulation of genes in the TCR signaling pathway in PTCL, a common feature of chronically activated T cells. Targeting TCR signaling pathway in lymphoma cells, either with cyclosporine A or anti-CD1d blocking antibody, prolonged mice survival. Importantly, we identified human CD1d-restricted lymphoma cells within Vδ1 TCR-expressing PTCL. These results define a new subtype of PTCL and pave the way for the development of blocking anti-CD1d antibody for therapeutic purposes in humans.},

keywords = {cytometry},

pubstate = {published},

tppubtype = {article}

}