Publications by authors named "Pascaud J"

Objectives: The RNA epitranscriptomic modification known as -methyladenosine (mA) represents a novel mechanism of gene regulation that is poorly understood in human autoimmune diseases. Our research explores the role of this RNA mA modification in salivary gland epithelial cells (SGEC) and its impact on the pathogenesis of Sjögren's disease (SjD).

Methods: SGECs from SjD patients and controls were analysed for mA writers METTL3 and METTL14 expression using RNA-seq, quantitative PCR and immunohistochemistry.

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Purinergic receptors and NOD-like receptor protein 3 (NLRP3) inflammasome regulate inflammation and viral infection, but their effects on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection remain poorly understood. Here, we report that the purinergic receptor P2X7 and NLRP3 inflammasome are cellular host factors required for SARS-CoV-2 infection. Lung autopsies from patients with severe coronavirus disease 2019 (COVID-19) reveal that NLRP3 expression is increased in host cellular targets of SARS-CoV-2 including alveolar macrophages, type II pneumocytes and syncytia arising from the fusion of infected macrophages, thus suggesting a potential role of NLRP3 and associated signaling pathways to both inflammation and viral replication.

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  • The study investigates the use of oto-acoustic emissions (OAE) as a non-invasive method for diagnosing intracranial hypotension (IH) in patients where traditional MRI results may be inconclusive.
  • Conducted over nearly nine years, the study found that out of 32 patients with suspected IH, 18 were confirmed to have the condition, with endolymphatic hydrops (ELH) detected in 15 of these cases.
  • However, the findings suggest that OAE is not reliable enough to differentiate IH from other similar conditions, indicating the need for further diagnostic methods.
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  • The study explores the role of microRNA-155 (miR-155) in rheumatoid arthritis (RA), specifically how its increased expression may hinder monocyte polarization into anti-inflammatory macrophages.
  • Researchers tested the therapeutic effects of antagomiR-155-5p, a molecule designed to inhibit miR-155, using PEGylated liposomes in two mouse models of RA.
  • Results showed that injecting these liposomes reduced arthritis symptoms and improved the differentiation of bone marrow monocytes into anti-inflammatory macrophages, indicating a potential treatment strategy for RA in humans.
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Salivary gland epithelial cells (SGECs) play an active role in primary Sjogren's syndrome (pSS) pathogenesis. Quantitative and qualitative abnormalities of saliva might expose SGECs to chronic hyperosmolarity. We aimed to decipher the links between hyperosmolar stimulation of SGECs and lymphocytic infiltration of the salivary glands (SG) observed in pSS.

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Objective: Janus kinase inhibitors (JAKi) are efficacious in RA but concerns regarding the risk of cancer associated with their exposure have recently emerged. Given the role of NK cells in antitumour response, we investigated the impact of JAKi [tofacitinib (TOFA), baricitinib (BARI), upadacitinib (UPA) and filgotinib (FIL)] on NK cells.

Methods: We first performed an ex vivo phenotype of NK cells in RA patients treated with TOFA, BARI or MTX.

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Objective: Antibody response to the messenger RNA (mRNA) COVID-19 vaccine has been shown to be diminished in rituximab (RTX)-treated patients. We undertook this study to compare humoral and T cell responses between healthy controls, patients with autoimmune diseases treated with RTX, and those treated with other immunosuppressants, all of whom had been vaccinated with 2 doses of the mRNA COVID-19 vaccine.

Methods: We performed anti-spike IgG and neutralization assays just before and 28 days after the second BNT162b2 (Pfizer-BioNTech) vaccine dose.

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  • The study investigates the risk of lymphoma in rheumatoid arthritis patients receiving different types of tumor necrosis factor inhibitors (TNFi), focusing on monoclonal anti-TNF antibodies versus soluble TNF receptors.
  • Using a mouse model of autoimmunity, researchers found that prolonged treatment with monoclonal anti-TNF antibodies significantly increased lymphoma risk compared to control groups and those treated with soluble TNF receptors.
  • Results indicate lower splenic macrophage infiltration in the monoclonal antibody group, suggesting the need for careful monitoring of lymphoma development in patients with B cell-driven autoimmune diseases undergoing long-term treatment with these antibodies.
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Objective: Primary Sjögren's syndrome (SS) is characterized by a lymphocytic infiltration of salivary glands (SGs) and the presence of an interferon (IFN) signature. SG epithelial cells (SGECs) play an active role in primary SS pathophysiology. We undertook this study to examine the interactions between SGECs and T cells in primary SS and the role of the interleukin-7 (IL-7)/IFN axis.

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Objective: Primary Sjögren's syndrome (pSS) is characterised by chronic hyperactivation of B lymphocytes. Salivary gland epithelial cells (SGECs) could play a role in promoting B-lymphocyte activation within the target tissue. We aimed to study the interactions between SGECs from patients with pSS or controls and B lymphocytes.

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Proinflammatory macrophages and miR-155 are increased in patients with rheumatoid arthritis (RA). We studied membrane TNF (mTNF) expression on blood monocytes, polarization into macrophages, miR-155 expression, and the effect of anti-TNF on these biomarkers in RA patients. Sixty-seven RA patients and 109 controls (55 healthy, 54 with spondyloarthritis and connective tissue diseases) were studied.

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Objectives: TNF inhibitors (TNFi) can induce anti-drug antibodies (ADA) in patients with autoimmune diseases (AID) leading to clinical resistance. We explored a new way of using methotrexate (MTX) to decrease this risk of immunisation.

Methods: We treated BAFF transgenic (BAFFtg) mice, a model of AID in which immunisation against biologic drugs is high, with different TNFi.

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Rotation or Change of Biotherapy After First Anti-TNF Treatment Failure for Rheumatoid Arthritis (ROC), registered 22 October 2009, NCT01000441.

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Objectives: Rheumatoid arthritis (RA) is associated with an increased risk of lymphoma linked to activity of the disease. Immunosuppressive drugs have been suspected to induce an additional risk. Since, NK cells have been recently shown to participate to anti-lymphoma immunosurveillance, we aimed to assess if anti-TNF might impact their anti-lymphoma activity.

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Endothelial Colony Forming Cells (ECFCs), a distinct population of Endothelial Progenitor Cells (EPCs) progeny, display phenotypic and functional characteristics of endothelial cells while retaining features of stem/progenitor cells. Cord blood-derived ECFCs (CB-ECFCs) have a high clonogenic and proliferative potentials and they can acquire different endothelial phenotypes, this requiring some plasticity. These properties provide angiogenic and vascular repair capabilities to CB-ECFCs for ischemic cell therapies.

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Antiserum from rabbits immunised with pure human fibrinogen was affinity purified on immobilised fibrin fragment E (FFE). This FFE antibody (Ab) induced significant growth inhibition of a human cancer xenograft in mice and suppression of tumour angiogenesis, leaving no formed vessels and only CD31-staining endothelial fragments in place. Tubule formation of HUVEC on MatrigelTM was also significantly inhibited by FFE Ab.

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A prospective study was conducted in 23 patients to evaluate magnetic resonance imaging versus computed tomography and plain film radiography for the early detection of sacroiliitis in patients with spondylarthropathy and an Amor score of less than 6. Computed tomography was significantly better than the other two techniques despite some false-positive results, particularly in patients older than 40 years. Magnetic resonance imaging lacked sensitivity for detecting elementary lesions, particularly of the cartilage, but demonstrated clearly that the earliest abnormality was edema of the subchondral bone.

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We report two cases of Pulmonary Hemosiderosis. The first patient (adult male) had an angiosarcoma of the left auricle and developed pulmonary arterial hypertension, was treated by surgery and chemotherapy. The other patient (adult female) suffered from Idiopathic Pulmonary Hemosiderosis (IPH) and had been treated by corticosteroids for fifteen years, with one acute episode during this period.

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The indications for treatment of idiopathic necrosis of the hip depend on the stage of development of the lesion, its extent and the site of the necrotic area. Digital computerised tomography with horizontal sections at five millimetre intervals from the upper to the lower pole of the femoral head is of value in the determination of these three features. For this purpose, fifteen femoral heads removed in the course of total hip arthroplasty were subjected to histological sections in parallel to those of the CT scan.

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