Precise Targeting of Autoantigen-Specific B Cells in Lupus Nephritis with Chimeric Autoantibody Receptor T Cells.

Despite conventional therapy, lupus nephritis (LN) remains a significant contributor to short- and long-term morbidity and mortality. B cell abnormalities and the production of autoantibodies against nuclear complexes like anti-dsDNA are recognised as key players in the pathogenesis of LN. To address the challenges of chronic immunosuppression associated with current therapies, we have engineered T cells to express chimeric autoantibody receptors (DNA-CAART) for the precise targeting of B cells expressing anti-dsDNA autoantibodies.

Thorough assessment of the effectiveness of belimumab in a large Spanish multicenter cohort of systemic lupus erythematosus patients.

Objectives: To provide an overview on the current use of belimumab (BLM) in SLE patients in clinical practice and to examine its efficacy in terms of standardized outcomes, drug survival, as well as patient and safety profiles.

Methods: A longitudinal retrospective multicenter cohort including SLE patients treated with BLM at 18 Spanish centers. Data was collected upon initiation of BLM, at 6 and 12 months after initiation, and at the last recorded visit.

Satisfaction and effectiveness of switching from intravenous to subcutaneous belimumab treatment in daily clinical practice.

Background: In 2017, belimumab (BEL) was approved in subcutaneous (SQ) administration. The effectiveness after switching from intravenous (IV) to SQ and patient satisfaction in daily clinical practice has not been studied. During the pandemic, patient follow-up and treatment were significantly affected, and some patients need a change from IV to SQ.

Disease activity drives divergent epigenetic and transcriptomic reprogramming of monocyte subpopulations in systemic lupus erythematosus.

Objectives: Systemic lupus erythematosus (SLE) is characterised by systemic inflammation involving various immune cell types. Monocytes, pivotal in promoting and regulating inflammation in SLE, differentiate from classic monocytes into intermediate and non-classic monocytes, assuming diverse roles and changing their proportions in inflammation. In this study, we investigated the epigenetic and transcriptomic profiles of these and novel monocyte subsets in SLE in relation to activity and progression.

Small-Extracellular-Vesicle-Derived miRNA Profile Identifies miR-483-3p and miR-326 as Regulators in the Pathogenesis of Antiphospholipid Syndrome (APS).

Primary antiphospholipid syndrome (PAPS) is a systemic autoimmune disease associated with recurrent thrombosis and/or obstetric morbidity with persistent antiphospholipid antibodies (aPL). Although these antibodies drive endothelial injury and thrombophilia, the underlying molecular mechanism is still unclear. Small extracellular vesicles (sEVs) contain miRNAs, key players in intercellular communication.

Reduction of disease activity, corticosteroids use, and healthcare resource utilisation in patients with systemic lupus erythematosus treated with belimumab in clinical practice settings: OBSErve Spain multicentre study.

Introduction And Objectives: This OBSErve Spain study, a part of the international OBSErve programme, evaluated belimumab real-world use and effectiveness following 6 months of treatment in patients with active systemic lupus erythematosus (SLE) in clinical practice in Spain.

Materials And Methods: In this retrospective, observational study (GSK Study 200883), eligible patients with SLE receiving intravenous belimumab (10mg/kg) had their disease activity (physician assessed), SELENA-SLEDAI scores, corticosteroid use, and healthcare resource utilisation (HCRU), assessed after 6 months of treatment versus index (belimumab initiation) or 6 months pre-index.

Results: Overall, 64 patients initiated belimumab, mainly due to ineffectiveness of previous treatments (78.

Direct Oral Anticoagulants vs Vitamin K Antagonists in Patients With Antiphospholipid Syndromes: Meta-Analysis of Randomized Trials.

Background: The efficacy and safety of direct oral anticoagulants (DOACs) for patients with thrombotic antiphospholipid syndrome remain controversial.

Objectives: The authors performed a systematic review and meta-analysis of randomized controlled trials that compared DOACs with vitamin K antagonists (VKAs).

Methods: We searched PubMed, EMBASE, and Cochrane Central Register of Controlled Trials through April 9, 2022.

Downregulation of miR-885-5p Promotes NF-κB Pathway Activation and Immune Recruitment in Cutaneous Lupus Erythematosus.

Cutaneous lupus erythematosus (CLE) has a specific microRNA expression profile. MiR-885-5p has been found to be downregulated in the epidermis of CLE lesions; however, its biological role in the disease has not been studied. In this study, we show that miR-885-5p is markedly reduced in CLE keratinocytes (KCs) with IFN-α and UVB being strong miR-885-5p regulators in vitro.

Humoral and cellular response in convalescent COVID-19 lupus patients.

In SLE, underlying immune dysregulation and immunosuppression may increase the susceptibility to COVID-19 and impair the humoral and adaptive response. We aimed to characterize COVID-19 infection, identifying susceptibility and severity risk factors, assessing the presence of SARS-CoV-2 IgG antibodies and analyzing the cellular response. We established a prospective cohort of lupus patients to estimate the COVID-19 incidence compared to the reference general population.

Preventing organ damage in systemic lupus erythematosus: the impact of early biological treatment.

Introduction: One of the most important aims in the management of systemic lupus erythematosus (SLE) is to avoid or delay the accumulation of organ damage. The first five years after diagnosis are crucial for prognosis.

Areas Covered: This manuscript reviews available data on organ damage accrual in SLE and early therapeutic intervention as a possible strategy to prevent its long-term accrual.

What can we learn from DNA methylation studies in lupus?

During the past twenty years, a wide range of studies have established the existence of epigenetic alterations, particularly DNA methylation changes, in lupus. Epigenetic changes might have different contributions in children-onset versus adult-onset lupus. DNA methylation alterations have been identified and characterized in relation to disease activity and damage, different lupus subtypes and responses to drugs.

Thalidomide Exerts Anti-Inflammatory Effects in Cutaneous Lupus by Inhibiting the IRF4/NF-ҡB and AMPK1/mTOR Pathways.

Thalidomide is effective in patients with refractory cutaneous lupus erythematosus (CLE). However, the mechanism of action is not completely understood, and its use is limited by its potential, severe side-effects. Immune cell subset analysis in thalidomide's CLE responder patients showed a reduction of circulating and tissue cytotoxic T-cells with an increase of iNKT cells and a shift towards a Th2 response.

MicroRNAs in Several Cutaneous Autoimmune Diseases: Psoriasis, Cutaneous Lupus Erythematosus and Atopic Dermatitis.

MicroRNAs (miRNAs) are endogenous small non-coding RNA molecules that regulate the gene expression at a post-transcriptional level and participate in maintaining the correct cell homeostasis and functioning. Different specific profiles have been identified in lesional skin from autoimmune cutaneous diseases, and their deregulation cause aberrant control of biological pathways, contributing to pathogenic conditions. Detailed knowledge of microRNA-affected pathways is of crucial importance for understating their role in skin autoimmune diseases.

Real-World Effectiveness of Belimumab in the Treatment of Systemic Lupus Erythematosus: Pooled Analysis of Multi-Country Data from the OBSErve Studies.

Introduction: The real-world effectiveness of belimumab for systemic lupus erythematosus (SLE) in six countries was evaluated in the OBSErve program. The aim of this post hoc analysis (GSK study 206351) was to pool individual patient OBSErve data to further evaluate the effectiveness of belimumab in a large sample of patients with SLE.

Methods: OBSErve (Argentina, Canada, Germany, Spain, Switzerland, and the USA) enrolled adults ≥ 18 years of age with SLE, who were prescribed belimumab as part of standard therapy (index: date of belimumab initiation).

Efficacy of Thalidomide in Discoid Lupus Erythematosus: Insights into the Molecular Mechanisms.

Background: Thalidomide has been used successfully in a variety of chronic refractory inflammatory dermatological conditions with underlying autoimmune or infectious pathogenesis. It was first used for refractory discoid lupus erythematosus (DLE) in 1983 and has steadily grown since then.

Method: In this review, we describe the therapeutic benefits of thalidomide for DLE treatment and its biological properties.

Direct oral anticoagulants versus vitamin K antagonists in antiphospholipid syndrome: A meta-analysis.

Background: Anticoagulant treatment is recommended in patients with thrombosis and antiphospholipid syndrome (APS). Conflicting results have been reported on the role of direct oral anticoagulants (DOACs) in these patients. We performed a meta-analysis of randomized controlled trials (RCTs) focused on this issue.

The Urinary Exosomal miRNA Expression Profile is Predictive of Clinical Response in Lupus Nephritis.

Data on exosomal-derived urinary miRNAs have identified several miRNAs associated with disease activity and fibrosis formation, but studies on prognosis are lacking. We conducted a qPCR array screening on urinary exosomes from 14 patients with biopsy-proven proliferative lupus glomerulonephritis with a renal outcome of clinical response ( = 7) and non-response ( = 7) following therapy. Validation studies were performed by qRT-PCR in a new lupus nephritis (LN) cohort (responders = 22 and non-responders = 21).

Budget Impact Analysis Of Subcutaneous Belimumab In Patients With Systemic Lupus Erythematosus In Spain.

Objective: To evaluate the budget impact and the direct costs of the introduction of subcutaneous belimumab (SC) into the Spanish National Health Service (NHS) for patients with systemic lupus erythematosus (SLE) in Spain.

Methods: This study was conducted from the Spanish NHS perspective with a time horizon of 3 years. The budget impact analysis compared the cost difference between two scenarios: current market (standard therapy (ST) and intravenous belimumab (IV)) and other market in which patients switched from belimumab IV to belimumab SC until reaching 17% of the total market share.

Rivaroxaban Versus Vitamin K Antagonist in Antiphospholipid Syndrome: A Randomized Noninferiority Trial.

Background: The potential role of new oral anticoagulants in antiphospholipid antibody syndrome (APS) remains uncertain.

Objective: To determine whether rivaroxaban is noninferior to dose-adjusted vitamin K antagonists (VKAs) for thrombotic APS.

Design: 3-year, open-label, randomized noninferiority trial.

Urinary Neuropilin-1: A Predictive Biomarker for Renal Outcome in Lupus Nephritis.

At present, Lupus Nephritis (LN) is still awaiting a biomarker to better monitor disease activity, guide clinical treatment, and predict a patient's long-term outcome. In the last decade, novel biomarkers have been identified to monitor the disease, but none have been incorporated into clinical practice. The transmembrane receptor neuropilin-1 (NRP-1) is highly expressed by mesangial cells and its genetic deletion results in proteinuric disease and glomerulosclerosis.

An Exosomal Urinary miRNA Signature for Early Diagnosis of Renal Fibrosis in Lupus Nephritis.

For lupus nephritis (LN) management, it is very important to detect fibrosis at an early stage. Urinary exosomal miRNAs profiling can be used as a potential multi-marker phenotyping tool to identify early fibrosis. We isolated and characterised urinary exosomes and cellular pellets from patients with biopsy-proven LN ( = 45) and healthy controls ( = 20).

MicroRNA Expression Profiling Identifies miR-31 and miR-485-3p as Regulators in the Pathogenesis of Discoid Cutaneous Lupus.

Cutaneous lupus erythematosus is a common and disfiguring manifestation in systemic lupus erythematosus. Subacute cutaneous lupus erythematosus and discoid lupus erythematosus (DLE) are the most prevalent forms. Despite sharing histological similarities, clinically they differ in their course and prognosis, suggesting different pathogenesis.

Enteric-coated mycophenolate sodium versus azathioprine in patients with active systemic lupus erythematosus: a randomised clinical trial.

Objective: To compare the efficacy and safety of enteric-coated mycophenolate sodium (EC-MPS) versus azathioprine (AZA) in patients with active systemic lupus erythematosus (SLE) disease.

Methods: A multicentre, 24-month, superiority, open-label, randomised controlled trial (NCT01112215) was conducted with 240 patients (120 per arm) receiving either EC-MPS (target dose: 1440 mg/day) or AZA (target dose: 2 mg/kg/day) in addition to prednisone and/or antimalarials. The primary endpoint was the proportion of patients achieving clinical remission, assessed by SLE Disease Activity Index 2000 (SLEDAI-2K) and British Isles Lupus Assessment Group (BILAG), at 3 and 24 months.