Unraveling the molecular landscape of Erdheim-Chester disease: new insights from methylome and transcriptome integration.

Erdheim-Chester Disease (ECD) is a rare histiocytosis characterized by a wide spectrum of clinical manifestations. Although somatic mutations have been involved in ECD, its etiology remains poorly understood. This study aimed to identify novel molecular mechanisms involved in ECD through the first integrated methylome and transcriptome analysis.

Performance of SCORE2, QRISK3 and PREVENT equations in systemic lupus erythematosus.

BackgroundAssessment of contemporary cardiovascular risk scores using clinically relevant endpoints is lacking in systemic lupus erythematosus (SLE).AimThis study aimed to assess and compare the performances of SCORE2, QRISK3 and PREVENT equations in SLE.MethodsSLE patients with no prior atherosclerotic cardiovascular disease (ASCVD) who underwent a baseline cardiovascular risk assessment including coronary artery calcium (CAC) scoring at the French national SLE reference center between 2014 and 2024 were retrospectively included.

Serum interferon-beta level determined by an ultrasensitive electrochemiluminescence immunoassay is increased in clinically active and inactive systemic lupus erythematosus.

Type I interferons, which play an important role in the pathogenesis of various autoimmune diseases such as systemic lupus erythematosus (SLE), are expressed at very low levels under physiological conditions. In this study, we focused on IFN-beta (IFN) β-for its potential use as a biomarker of SLE activity and compared three different technologies for its quantification in the serum of healthy donors and patients with SLE. A total of 93 serum samples from healthy donors and 463 serum samples from lupus patients were tested using either ELISA, digital ELISA based on Single Molecule Array (Simoa®) technology, or a novel ultrasensitive immunoassay (S-Plex®) based on electrochemiluminescence.

Cluster analysis identifies three clinical patterns of patients with systemic autoimmune diseases and anti-Ku antibodies.

Objective: To determine distinct patterns of patients with autoimmune diseases harbouring anti-Ku antibodies and their respective prognosis.

Methods: Anti-Ku-positive patients were retrieved through four immunology departments. Clusters were derived from unsupervised multiple correspondence analysis, not including the disease's diagnosis, followed by hierarchical clustering.

Cluster analysis reveals the clinical spectrum of Erdheim-Chester disease.

Erdheim-Chester disease (ECD) is a clonal-inflammatory neoplasm driven by mutations in MAPK pathway proto-oncogenes, such as BRAF. Clinical manifestations are protean, affecting virtually every system. This cohort study analyzed 661 patients with ECD to classify them based on clinical features and mutational profiles using unsupervised clustering.

Characteristics of SARS-CoV-2-associated severe episodes of monoclonal gammopathy-associated capillary leak syndrome (Clarkson disease).

Background: Monoclonal gammopathy-associated capillary leak syndrome (MG-CLS) is a rare condition characterized by recurrent episodes of hypovolemic shock caused by a sudden increase in capillary permeability. The COVID-19 pandemic has been associated with a rise in MG-CLS episodes and increased mortality. We aimed to explore the association between MG-CLS and SARS-CoV-2 infection.

Population pharmacokinetic modelling of prednisolone in systemic lupus erythematosus patients: Analysis of exposure and disease activity.

Aims: Prednisone is a widely used glucocorticoid in the treatment of lupus, although its dosing is often determined empirically. Prednisolone, the active metabolite of prednisone, is found in its free form in the serum. The goal of this study was to develop a population pharmacokinetic model in patients with systemic lupus erythematosus (SLE) to forecast free prednisolone concentrations and its association with disease activity.

Progressive repigmentation of hypopigmented lesions in discoid lupus erythematosus with anifrolumab: A report of two cases.

We report two cases of patients with refractory discoid lupus erythematosus (DLE) and dark skin phototypes who experienced progressive perifollicular repigmentation of depigmented lesions under anifrolumab therapy, with sustained improvement over 18 months. These observations highlight a potential novel effect of anifrolumab on cicatricial dyspigmentation in DLE. This effect may represent a valuable therapeutic option for DLE-related damage, particularly in patients with darker skin types.

SARS-CoV-2 lineage-dependent temporal phylogenetic distribution and viral load in immunocompromised and immunocompetent individuals.

Objectives: Mutational dynamics of SARS-CoV-2 in immunocompromised hosts, although well documented, remain a relatively unexplored mechanism. This study aims to compare the viral replication load and genetic diversity of SARS-CoV-2 in immunocompromised patients and non-immunocompromised individuals (NICs) from two major hospitals in Paris from January 2021 to May 2023.

Methods: Cycle threshold (CT) values were measured by TaqPath COVID-19 RT-PCR (Thermo Fisher Scientific).

Rapid Detection of Anti-IFN-α2 Autoantibodies Using a New Automated VIDAS Assay Prototype.

Autoantibodies neutralizing Type I interferons increase the risk of severe viral diseases and are linked to autoimmune conditions. The automated VIDAS assay is suitable for anti-IFN-α2 IgGs quantification, offering a swift, reliable, user-friendly, single test for clinical management.

Vascular liver disorders in patients with antiphospholipid syndrome: a national retrospective multicentre study.

Objective: Antiphospholipid syndrome (APS) is an acquired autoimmune prothrombotic condition. Vascular liver disorders (VLD), such as portal vein thrombosis (PVT), Budd-Chiari syndrome (BCS) and porto-sinusoidal vascular disorder (PSVD), are rare and related to an underlying hypercoagulable state in most cases. We aimed to describe the clinical and immunological features of APS patients with VLD.

CAR T-cell therapy in autoimmune diseases: where are we and where are we going?

Chimeric antigen receptor (CAR)-based therapies developed for the treatment of haematological malignancies have recently been repurposed to treat refractory systemic autoimmune diseases. In this Review we critically discuss the current data available on the use of CAR-based therapy in systemic autoimmune diseases, the current challenges, and the potential next steps toward their implementation into clinical practice. Beyond the targeting of B cells via CD19, we discuss the advantages and potential pitfalls of targeting plasma cells (B-cell Maturation Antigen or CD138) and other non-immune targets, such as fibroblast activated protein, and of aiming to restore immune homeostasis using CAR T regulatory cells.

Monocytic meningitis complicating histiocytosis and response to MEK-inhibitor: a case series.

Central nervous system (CNS) involvement is common in histiocytosis, yet cerebrospinal fluid (CSF) analysis often yields normal results. We present three cases of monocytic meningitis associated with histiocytosis. The first patient was diagnosed with Erdheim-Chester disease (ECD) and exhibited evidence of a MAP2K1 mutation, concomitant with chronic myelomonocytic leukemia.

Anti-RNApol3-Associated myocarditis: an emerging disease linking autoimmunity and infection.

Background: Fulminant myocarditis (FM) is a severe condition primarily triggered by viruses. Anti-RNA polymerase III autoantibodies (RNApol3) which are typically found in patients with severe systemic sclerosis, have been reported in patients with influenza-related FM. Our objective is to provide additional insight into RNApol3-associated FM.

Diseases associated with anti-centromere protein F (anti-CENP-F) antibodies: Insights from a large cohort study.

Introduction: Antinuclear antibodies (ANA) exhibit diverse specificities and are crucial biomarkers in autoimmune disease assessment. Among ANA, anti-centromere protein-F (CENP-F) antibodies have garnered interest due to their association with malignancies. This study aims to characterize the clinical and biological profiles of a large cohort of anti-CENP-F positive patients and evaluate associated diagnoses.

Role of clonal inflammatory microglia in histiocytosis-associated neurodegeneration.

Langerhans cell histiocytosis (LCH) and Erdheim-Chester disease (ECD) are clonal myeloid disorders associated with mitogen-activated protein (MAP)-kinase-activating mutations and an increased risk of neurodegeneration. We found microglial mutant clones in LCH and ECD patients, whether or not they presented with clinical symptoms of neurodegeneration, associated with microgliosis, astrocytosis, and neuronal loss, predominantly in the rhombencephalon gray nuclei. Neurological symptoms were associated with PU.

Interferon-α biological activity is associated with disease activity and risk of flare in cutaneous lupus erythematosus: A monocentric study of 184 patients.

Background: Cutaneous lupus erythematosus (CLE) is associated with unpredictable flares and may induce permanent damage. There is currently no biomarker routinely available in CLE.

Objective: To evaluate the performance of interferon-α (IFN-α) biological activity as biomarker of CLE activity and risk of flare.