Jacques-Olivier Pers

• DDS, PhD
• Université de Bretagne Occidentale

Background Interpreting biological system changes requires interpreting vast amounts of multi-omics data. While user-friendly tools exist for single-omics analysis, integrating multiple omics still requires bioinformatics expertise, limiting accessibility for the broader scientific community. Results BiomiX tackles the bottleneck in high-throughpu...

Objectives Systemic sclerosis (SSc) is a heterogeneous disease, complicating its management. Its complexity and the insufficiency of clinical manifestations alone to delineate homogeneous patient groups further challenge this task. However, autoantibodies could serve as relevant markers for the pathophysiological mechanisms driving the disease. Ide...

The heterogeneity of systemic lupus erythematosus (SLE) can be explained by epigenetic alterations that disrupt transcriptional programs mediating environmental and genetic risk. This study evaluated the epigenetic contribution to SLE heterogeneity considering molecular and serological subtypes, genetics and transcriptional status, followed by drug...

Background Sjögren’s disease (SjD) is a heterogenous autoimmune disease, with a wide range of symptoms, from dryness, fatigue, pain, to systemic manifestations, and an increased risk of lymphoma. Recently, three clusters of patients with SjD have been described based on unsupervised clustering analysis according to symptoms, clinical signs and biol...

Background In our previous Sjögren’s Disease (SjD) Genome-Wide Association Study (GWAS) in European populations, significant single nucleotide polymorphism (SNP) peaks were identified between PRDM1 and ATG5 [1]. ATG5 is an autophagy-related protein that plays a crucial role in neutrophil extracellular trap (NET) formation, degranulation, and limiti...

Background Sjögren’s disease (SjD) is a complex systemic autoimmune disease with substantial morbidity and 21 known genetic associations. The International Sjögren’s Genetics Network (SGENE) is a growing international collaboration focused on understanding how genetic variants influence SjD pathology. As sample sizes increase, we are focusing our e...

Background Primary Sjögren’s syndrome (pSS) is an autoimmune disease, known for its disabling effect and chronic course. One of the peculiar symptoms is the lachrymal glands dryness associated often but not limited to dry mouth, dental disorders, joint pain, fatigue, and, in severe cases, systemic complications. The most relevant clinical feature i...

Background Sjögren’s disease (SjD) presents an unmet medical challenge as there is currently no cure. Despite advances in understanding the immunopathogenesis of SjD, there is still a pressing need to identify novel biomarkers and therapeutic targets, for better patient stratification and personalized treatment. Objectives To create a fully-detail...

Objective Tissue-resident memory cells (Trm) are a subset of T cells residing persistently and long-term within specific tissues that contribute to persistent inflammation and tissue damage. We characterised the phenotype and function of Trm and the role of CD103 in primary Sjogren’s syndrome (pSS). Methods In both pSS and non-pSS sicca syndrome p...

Imaging mass cytometry (IMC) is a metal mass spectrometry-based method allowing highly multiplex immunophenotyping of cells within tissue samples. However, some limitations of IMC are its 1-µm resolution and its time and costs of analysis limiting respectively the detailed histopathological analysis of IMC-produced images and its application to sma...

Objectives To unveil biological milieus underlying low disease activity (LDA) and remission versus active systemic lupus erythematosus (SLE). Methods We determined differentially expressed pathways (DEPs) in SLE patients from the PRECISESADS project (NTC02890121) stratified into patients fulfilling and not fulfilling the criteria of (1) Lupus LDA...

Objective The biologic diagnosis of primary Sjögren disease (SjD) mainly relies on anti‐Ro60/SSA antibodies, whereas the significance of anti‐Ro52/TRIM21 antibodies currently remains unclear. The aim of this study was to characterize the clinical, serological, biologic, transcriptomic, and interferon profiles of patients with SjD according to their...

Background: Immune checkpoint inhibitors (ICI) have significantly improved cancer prognosis but can lead to immune-related adverse events (irAE), including cutaneous manifestations affecting 30% to 60% of ICI-treated patients. However, the physiopathology of cutaneaous irAE remains unclear. Objective: This study investigated the immune infiltration...

Fine mapping and bioinformatic analysis of the DDX6-CXCR5 genetic risk association in Sjogrens Disease (SjD) and Systemic Lupus Erythematosus (SLE) identified five common SNPs with functional evidence in immune cell types: rs4938573, rs57494551, rs4938572, rs4936443, rs7117261. Functional interrogation of nuclear protein binding affinity, enhancer/...

Background The diagnosis of primary Sjögren Disease (SjD) is currently based on a combination of clinical, histological and biological findings [1]. Current thinking supports anti-Ro60 antibodies as the most specific serum marker, while the impact of anti-Ro52 remains unclear [2]. Objectives The aim of this study was to characterize the clinical,...

Background Within the group of inflammatory myopathies, Inclusion-Body Myositis (IBM) is a distinct pathology with clinical and histological features very different from other entities. In the literature, an association between primary Sjögren’s syndrome (pSS) and IBM has been previously reported. Objectives The aim of our study was to compare the...

Objective Autoreactive B cells are responsible for antineutrophil cytoplasmic antibody (ANCA) production in ANCA‐associated vasculitis (AAV). Rituximab (RTX) depletes circulating B cells, including autoreactive B cells. We aimed to evaluate changes and associations with relapse of the circulating autoreactive B cell pool following therapeutic B cel...

The recent emergence of imaging mass cytometry technology has led to the generation of an increasing amount of high-dimensional data and, with it, the need for suitable performant bioinformatics tools dedicated to specific multiparametric studies. The first and most important step in treating the acquired images is the ability to perform highly eff...

The humoral response is frequently dysfunctioning in autoimmunity with a frequent rise in total serum immunoglobulins, among which are found autoantibodies that may be pathogenic by themselves and/or propagate the inflammatory reaction. The infiltration of autoimmune tissues by antibody-secreting cells (ASCs) constitutes another dysfunction. The kn...

Introduction Primary Sjögren’s syndrome (pSS) is a systemic autoimmune disease characterized by exocrine gland dysfunction. No therapeutic strategy is sufficient on its own for the management of dry mouth and therapeutic innovations are required. Methods This Predelfi study was a single-center, prospective, comparative, randomized, double-blind, c...

Regulatory B (Breg) cells can dampen inflammation, autoreactivity and transplant rejection. We investigated the frequencies, phenotypes and function of Breg cells in granulomatosis with polyangiitis (GPA) to gain further knowledge to whether there are numerical alterations or limitations of their ability to regulate T-cell function. Frequencies and...

Objective: Persistent inflammation can promote the development of tertiary lymphoid structures (TLS) within tissues resembling the secondary lymphoid organs (SLO) as lymph nodes (LN). The composition of the TLS across different organs and diseases could be of pathophysiological and medical interest. In this work, we compared TLS to SLO and between...

Primary Sjögren’s syndrome (pSS) is characterized by an autoimmune epithelitis associated with chronic inflammation of the exocrine glands. Alterations of extra-glandular functions in pSS is associated with lymphocytic infiltrates that invade the epithelial structures of affected organs. Within epithelial tissue, the expression of class II major hi...

Despite the growing interest in salivary metabolomics, few studies have investigated the impact of aging on the salivary metabolome. The alterations in metabolic pathways that occur with aging are likely to be observed in pathologies affecting older people and may interfere with the search for salivary biomarkers. It is therefore important to inves...

Copy number (CN) polymorphisms of complement C4 play distinct roles in many conditions, including immune-mediated diseases. We investigated the association of C4 CN with systemic sclerosis (SSc) risk. Imputed total C4, C4A, C4B, and HERV-K CN were analyzed in 26,633 individuals and validated in an independent cohort. Our results showed that higher...

Objective: To determine whether repeated minor salivary gland biopsy (MSGB) has a clinical diagnostic utility in patients with suspicion of Sjögren’s syndrome (SS). Methods: Clinical, biological, pathological data and physician’s diagnosis after each MSGB from patients with suspected primary or secondary SS who had benefited from 2 MSGB at Brest Un...

Objective Anti‐Ro autoantibodies are among the most frequently detected extractable nuclear antigen autoantibodies, mainly associated with primary Sjögren's syndrome (SS), systemic lupus erythematosus (SLE), and undifferentiated connective tissue disease (UCTD). This study was undertaken to determine if there is a common signature for all patients...

Systemic lupus erythematosus (SLE) and primary Sjögren’s syndrome (pSS) are two autoimmune diseases characterised by the production of pathogenic autoreactive antibodies. Their aetiology is poorly understood. Nevertheless, they have been shown to involve several factors, such as infections and epigenetic mechanisms. They also likely involve a physi...

Background Clinical trials are essential in medical science and are currently the most robust strategy for evaluating the effectiveness of a treatment. However, some of these studies are less reliable than others due to flaws in their design. Assessing the robustness of a clinical trial can be a very complex and time-consuming task, with factors su...

Background Anti-SSA/Ro autoantibodies are among the most frequently detected extractable nuclear antigen autoantibodies and have mainly been associated with primary Sjögren’s syndrome (pSS), systemic lupus erythematosus (SLE) and undifferentiated connective tissue disease (UCTD). Objectives Is there a common signature to all patients expressing an...

B cells have a central and dual role in the physio-pathological mechanisms of periodontitis. They take part in the elimination of the periodontal germs, the induction of tissue destructions and the regulation of the immune response. B cells play an essential role in the destruction of alveolar bone in periodontitis by immunomodulation, rather than...

Imaging mass cytometry (IMC) enables the in situ analysis of in-depth-phenotyped cells in their native microenvironment within the preserved architecture of a single tissue section. To date, it permits the simultaneous analysis of up to 50 different protein- markers targeted by metal-conjugated antibodies. The application of IMC in the field of can...

Regulatory B cells (Bregs) have been highlighted in very different pathology settings including autoimmune diseases, allergy, graft rejection, and cancer. Improving tools for the characterization of Bregs has become the main objective especially in humans. Transitional, mature B cells and plasma cells can differentiate into IL-10 producing Bregs in...

Résumé Le syndrome de Gougerot-Sjögren primaire (SSpp) peut s’apparenter à une épithélite auto-immune caractérisée par une inflammation chronique des glandes exocrines. Les altérations des fonctions glandulaires et extra-glandulaires du SSp sont associées à des infiltrats lympho-plasmocytaires qui envahissent les structures épithéliales des organes...

For many decades, the clinical unmet needs of primary Sjögren’s Syndrome (pSS) have been left unresolved due to the rareness of the disease and the complexity of the underlying pathogenic mechanisms, including the pSS-associated lymphomagenesis process. Here, we present the HarmonicSS cloud-computing exemplar which offers beyond the state-of-the-ar...

Primary Sjögren’s syndrome (SS) is a systemic autoimmune disease characterized by lymphocytic infiltration and damage of exocrine salivary and lacrimal glands. The etiology of SS is complex with environmental triggers and genetic factors involved. By conducting an integrated multi-omics study, we confirmed a vast coordinated hypomethylation and ove...

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...

Introduction Le nombre croissant de publications dans le domaine de l’immunologie souligne la nécessité d’un filtrage automatique des publications afin d’extraire rapidement les informations intégrées dans ce corpus de littérature scientifique. Patients et méthodes Pour effectuer une revue systématique de la littérature, nous avons utilisé BIBOT,...

Further observations support the role of environmental factors in autoimmune diseases via the alteration of the epigenetic machinery. In this context, ultraviolet light, smoking, chemicals, and psychological stress have been described as likely examples of this phenomenon. For this study, we took advantage of the PRECISESADS IMI project, which gath...

Introduction: The complex pathophysiology of autoimmune diseases (AIDs) is being progressively deciphered, providing evidence for a multiplicity of pro-inflammatory pathways underlying heterogeneous clinical phenotypes and disease evolution. Areas covered: Treatment strategies involving drug combinations are emerging as a preferred option to achiev...

Background: Little is known about the autoreactive B cells in anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). We aimed to investigate tolerance checkpoints of circulating antigen-specific proteinase 3 (PR3+) B cells. Methods: Multicolor flow cytometry in combination with bioinformatics and functional in vitro studies wer...

Metabolic pathways have been studied for a while in eukaryotic cells. During glycolysis, glucose enters into the cells through the Glut1 transporter to be phosphorylated and metabolized generating ATP molecules. Immune cells can use additional pathways to adapt their energetic needs. The pentose phosphate pathway, the glutaminolysis, the fatty acid...

Mesenchymal stem cells (MSCs) are ubiquitous in the human body. Mesenchymal stem cells were initially isolated from bone marrow and later from other organs such as fatty tissues, umbilical cords, and gingiva. Their secretory capacities give them interesting immunomodulatory properties in cell therapy. Some studies have explored the use of MSCs to t...

Objective The effector T cell and B cell cytokine networks have been implicated in the pathogenesis of systemic autoimmune diseases, but the association of these cytokine networks with the heterogeneity of clinical manifestations and immune profiles has not been carefully examined. This study was undertaken to examine whether cytokine profiles can...

Abatacept mimics natural CD152 and competes with CD28 for binding to CD80/CD86 on APC, such as B cells, thereby preventing T cell activation. However, its potential impact on B cells has not been identified. The aim of this study was to assess whether abatacept can potentiate the immunoregulatory properties of B cells in vitro and in patients with...

Chronic lymphocytic leukemia (CLL) is characterized by significant biologic and clinical heterogeneity. This study was designed to explore CLL B‐cells’ proteomic profile in order to identify biologic processes affected at an early stage and during disease evolution as stable or progressive. Purified B cells from 11 untreated CLL patients were teste...

Antibody-secreting cells (ASC) are divided into two principal subsets, including the long-lived plasma cell (PC) subset residing in the bone marrow and the short-lived subset, also called plasmablast (PB). PB are described as a proliferating subset circulating through the blood and ending its differentiation in tissues. Due to their inherent hetero...

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...

The integrative analysis of tumor immune microenvironment (TiME) components, their interactions and their microanatomical distribution is mandatory to better understand tumor progression. Imaging Mass Cytometry (IMC) is a high dimensional tissue imaging system which allows the comprehensive and multiparametric in situ exploration of tumor microenvi...

Immunological memory is essential for effective immune protection upon antigen rechallenge. Memory B cells encompass multiple subsets, heterogeneous in terms of phenotypes, origins and precursors, anatomical localization, and functional responses. B-cell responses are conditioned by micro-environmental signals, including cytokines. Here, we analyze...

Autoimmune disease development depends on multiple factors, including genetic and environmental. Abnormalities such as sialylation levels and/or quality have been recently highlighted. The adjunction of sialic acid at the terminal end of glycoproteins and glycolipids is essential for distinguishing between self and non-self-antigens and the control...

Immune system provides the mechanisms for attacking foreign invaders, eliminating autologous toxic substances and offering self-tolerance.

Autoimmune disorders result from the attack of the immune system against self, since patients with these diseases have lost a major characteristic of the immune system, the immune tolerance (ability not to react against self). They can affect one organ (organ-specific) or many organs (systemic). The majority of autoimmune rheumatic diseases are sys...

IntroductionOral administration of pilocarpine enhances salivary flow in sicca patients but its effect upstream on ultrasound (US) of salivary glands (SG) and downstream on periodontium remain unknown. Methods Sicca patients were prospectively included. Echostructural and vascularization of SG were assessed using B mode and pulsed Doppler (USPD). V...

Introduction Les lymphocytes B (LB) sont au centre des mécanismes des maladies auto-immunes. Ces maladies sont définies par une rupture de la tolérance du soi du système immunitaire chez les patients et la production d’auto-anticorps contre des composants de son propre organisme. Des auto-anticorps spécifiques sont détectables chez tous les sujets...

Autoimmune diseases (AIDs) share similar serological, clinical, and radiological findings, but, behind these common features, there are different pathogenic mechanisms, immune cells dysfunctions, and targeted organs. In this context, multiple lines of evidence suggest the application of precision medicine principles to AIDs to reduce the treatment...

For health professionals, repeated SARS‐CoV‐2 RNA detection through PCR combined with properly validated serologic assays for the presence of anti‐IgM and anti‐IgG antibodies should be mandatory.

Primary Sjögren’s syndrome (SS) is a systemic autoimmune disease characterized by lymphocytic infiltration and damage of exocrine salivary and lacrimal glands. The etiology of SS is complex with environmental triggers and genetic factors involved. By conducting an integrated multi-omics study we identified vast coordinated hypomethylation and overe...

Resumen El síndrome de Sjögren primario es una enfermedad sistémica autoinmunitaria que se caracteriza principalmente por una lesión inflamatoria de las glándulas salivales y lacrimales que provoca un síndrome de sequedad ocular y bucal, pero que también puede afectar a múltiples órganos. A veces puede estar asociado con otra enfermedad sistémica;...

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 standar...

IgM antibodies against phosphorylcholine (anti-PC) and malondialdehyde (anti-MDA) may have protective properties in cardiovascular and rheumatic diseases. We here compare these antibodies in systemic rheumatic conditions and study their properties. Anti-PC and anti-MDA was measured using ELISA in patients with SLE (374), RA (354), Mixed connective...

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 dif...

Background The analysis of annotated transcripts from genome-wide expression studies data is of paramount importance to understand the molecular phenomena underlying the occurrence of complex diseases, such as systemic sclerosis (SSc). Objectives To perform whole-blood transcriptome and pathway analysis on whole-blood (WB) RNA collected in two coh...

Background B cells play a crucial role in the pathogenesis of systemic autoimmunity through various effector functions, including auto-antibody production, secretion of pro-inflammatory cytokines and antigen presentation to T cells. Interferon alpha (IFNα), mainly produced by innate cells (Menon et al., 2016), and interleukin (IL)-21 which is secre...

Background Objectives 1. This study, developed within the Innovative Medicines Initiative Joint Undertaking project PRECISESADS framework, aimed to identify specific molecular profiles involved in the enhanced CV-risk present in SLE patients and to analyze the relevance of the sustained positivity for anti-dsDNA on the establishment of their ather...

Background Proteinase 3 (PR3)-reactive B cells are present in PR3-ANCA-associated vasculitis (AAV) at levels higher than healthy controls. Objectives To evaluate the dynamics of the PR3-reactive B cell repopulation in patients with PR3-AAV after treatment with rituximab, and to analyze possible associations between these immunological changes and...

Background B cells play a central role in many autoimmune diseases (AIDs) including ANCA-associated vasculitis (AAV) and primary Sjögren’s syndrome (pSS). Most of the research that has been conducted on AID has focused on the production, secretion, and pathogenicity of auto-antibodies, but little is known on the characteristics of autoreactive B ce...

Résumé Objectif La parotidomégalie est un critère du score d’activité du syndrome de Gougerot-Sjögren primitif (ESSDAI, EULAR Sjögren Syndrome Disease Activity Index) défini par l’EULAR. La valeur seuil de longueur a été fixée à 3 cm pour les glandes parotides et à 2 cm pour les glandes submandibulaires. Cependant la fiabilité de l’évaluation clin...

Background Clinical heterogeneity, a hallmark of systemic autoimmune diseases (SADs) impedes early diagnosis and effective treatment, issues that may be addressed if patients could be grouped into a molecular defined stratification. Methods With the aim of reclassifying SADs independently of the clinical diagnoses, unsupervised clustering of integ...

Background: Clinical heterogeneity, a hallmark of systemic autoimmune diseases (SADs) impedes early diagnosis and effective treatment, issues that may be addressed if patients could be grouped into a molecular defined stratification. Methods: With the aim of reclassifying SADs independently of the clinical diagnoses, unsupervised clustering of inte...

Rheumatologists use classification criteria to separate patients with inflammatory rheumatic diseases (IRD). They change over time, and the concepts of the diseases also change. The paradigm is currently moving as the goal of classification in the future will be more to select which patients may be relevant for a specific treatment rather than to d...

The innate B cell (IBC) population is heterogeneous and involved in the primary immune response. IBC functions include a high ability to produce natural antibodies with IgM isotype, the elimination of apoptotic cells, and a capacity to be cognate help to T cells. Among IBC subsets, B-1 cells and marginal zone B cells are the main producers of IgM,...

Introduction Le nombre d’articles publiés chaque année augmente de manière rapide et constante. Réaliser manuellement une revue de la littérature systématisée devient une tâche de plus en plus ardue, en particulier si le sujet est complexe. Matériel et méthodes Nous avons comparé les résultats d’une recherche classique et d’une recherche similaire...