Subset of DN Memory B Cells Expressing Low Levels of Inhibitory Receptor BTLA Is Enriched in SLE Patients.

The dialogue between T and B cells can be regulated by different mechanisms, such as co-inhibitory receptors, which therefore play a crucial role in preventing autoimmune diseases such as systemic lupus erythematosus (SLE). B and T lymphocyte attenuator (BTLA) is a co-inhibitory receptor expressed on many myeloid and lymphoid cells. Although peripheral B cells express a very high amount of BTLA, previous works in the context of autoimmunity mainly focused on T cells, and whether BTLA expression on B cells plays a role in the lupus pathogenesis is still unclear.

The Potential Of Autologous Patient-Derived Circulating Extracellular Vesicles To Improve Drug Delivery In Rheumatoid Arthritis.

Recognizing the need for innovative therapeutic approaches in the management of autoimmune diseases , our current investigation explores the potential of autologous extracellular vesicles (EVs), derived from blood of rheumatoid arthritis (RA) patients, to serve as therapeutic vectors to improve drug delivery. We found that circulating EVs derived from arthritic mice (Collagen-induced arthritis model) express the joint/synovia homing receptor, αVβ3 integrin. Importantly, both autologous labelled EVs, derived from blood of arthritic mice (Collagen antibody-induced arthritis model) and healthy mice-derived EVs, exhibit targeted migration toward inflamed synovia without infiltrating healthy joints, as demonstrated by an in-vivo imaging system.

A machine learning tool for early identification of celiac disease autoimmunity.

Identifying which patients should undergo serologic screening for celiac disease (CD) may help diagnose patients who otherwise often experience diagnostic delays or remain undiagnosed. Using anonymized outpatient data from the electronic medical records of Maccabi Healthcare Services, we developed and evaluated five machine learning models to classify patients as at-risk for CD autoimmunity prior to first documented diagnosis or positive serum tissue transglutaminase (tTG-IgA). A train set of highly seropositive (tTG-IgA > 10X ULN) cases (n = 677) with likely CD and controls (n = 176,293) with no evidence of CD autoimmunity was used for model development.

Genome-wide epigenetic profiling and transcriptome analysis in pediatric Obstructive Sleep Apnea: A focus on Black female children.

Obstructive Sleep Apnea (OSA) is a common sleep-related breathing disorder characterized by airway obstruction during sleep. Diagnosing pediatric OSA is challenging, particularly in underrepresented populations, leading to disparities in treatment and long-term negative health outcomes. Our study aimed to identify alternative diagnostic tools by investigating genome-wide epigenetic changes and associated transcriptomic alterations in Black female, pediatric patients with OSA.

Diaci v3.0: chromosome-level assembly, de novo transcriptome, and manual annotation of Diaphorina citri, insect vector of Huanglongbing.

Background: Diaphorina citri is an insect vector of "Candidatus Liberibacter asiaticus" (CLas), the gram-negative bacterial pathogen associated with citrus greening disease. Control measures rely on pesticides with negative impacts on the environment, natural ecosystems, and human and animal health. In contrast, gene-targeting methods have the potential to specifically target the vector species and/or reduce pathogen transmission.

The human glucocorticoid receptor variant rs6190 promotes blood cholesterol and atherosclerosis.

Elevated cholesterol poses a significant cardiovascular risk, particularly in older women. The glucocorticoid receptor (GR), a crucial nuclear transcription factor that regulates the metabolism of virtually all major nutrients, harbors a still undefined role in cholesterol regulation. Here, we report that a coding single nucleotide polymorphism (SNP) in the gene encoding the GR, , associated with increased cholesterol levels in women according to UK Biobank and All Of Us datasets.

Non-invasive assessment of portal hypertension in patients with primary biliary cholangitis is affected by severity of cholestasis.

Background&aims: Non-invasive tests (NITs) for ruling-out clinical significant portal hypertension (CSPH) and high-risk varices (HRV) in patients with primary biliary cholangitis(PBC) and compensated advanced chronic liver disease (cACLD) are lacking. We evaluated NITs in these patients and the influence of cholestasis on their performance.

Methods: Consecutive patients from the "Italian PBC registry" and two UK large-volume PBC referral centres with upper endoscopy within 6 months from biochemical evaluation and transient elastography were included.

Efficacy and safety of guselkumab in patients with active lupus nephritis: results from a Phase 2, randomized, placebo-controlled study.

Objective: Evaluate the efficacy and safety of guselkumab, an interleukin (IL)-23 inhibitor, in a Phase 2, multicentre, randomized, double-blind, placebo-controlled study of patients with active lupus nephritis (LN).

Methods: Adults (18-75 years) with active LN (Class III-IV proliferative nephritis [kidney biopsy] and urine protein-to-creatinine ratio [UPCR)] of ≥ 1 mg/mg despite standard-of-care therapy) were randomized (1:1; planned sample = 60) to receive intravenous infusions of guselkumab 400 mg or placebo at Weeks 0, 4, and 8, then subcutaneous injections (guselkumab 200 mg or placebo) at Week12 and every 4 weeks through Week48 in addition to their background therapy. The primary end point was achievement of ≥ 50% decrease in proteinuria from baseline at Week24.

Vasodilator drugs and heart-related outcomes in systemic sclerosis: an exploratory analysis.

Background And Aims: Systemic sclerosis (SSc) is an autoimmune connective disease characterised by excessive extracellular matrix deposition and widespread skin and internal organ fibrosis including various cardiac manifestations. Heart involvement is one of the leading causes of death among patients with SSc. In this study, we aimed to assess the effect of various vasodilator treatments.

Anti-vitamin D antibodies.

Background: Low vitamin D levels are commonly observed in autoimmune diseases, suggesting a potential role in disease pathogenesis. The presence of anti-vitamin D antibodies may contribute to these deficiencies and influence autoimmune processes.

Objective: To review and analyze studies investigating the occurrence of anti-vitamin D antibodies in autoimmune diseases.

The 330 risk loci known for systemic lupus erythematosus (SLE): a review.

An in-depth literature review of up to 2023 reveals 330 risk loci found by genetic association at ≤ 5 × 10, with systemic lupus erythematosus (SLE) in at least one study of 160 pertinent publications. There are 225 loci found in East Asian (EAS), 106 in European (EU), 11 in African-American (AA), 18 Mixed American (MA), and 1 in Egyptian ancestries. Unexpectedly, most of these associations are found to date at ≤ 5 × 10 in a single ancestry.

IFN-associated B cell hyperactivity is highly enriched in SLE patients harboring Sm/RNP antibodies.

Systemic Lupus Erythematosus (SLE) is an autoimmune disease characterized by an array of autoantibodies, in particular anti-nuclear antibodies (ANA). The disease is also hallmarked by an expansion of plasmablasts (PB) in peripheral blood. How these relate to autoantibody production is not clear.

Interconnected Pathways: Exploring Inflammation, Pain, and Cognitive Decline in Osteoarthritis.

The relationship among inflammation, pain, and cognitive decline in osteoarthritis (OA) patients is complex and has not been sufficiently explored; therefore, we undertook this research to evaluate how OA-related inflammation and pain affect cognitive functions, as well as to examine the potential of urinary markers as indicators of these conditions. This study examined fifty OA patients through clinical and cognitive assessments, morphological analyses, urinary biomarkers, and bioinformatics. Morphologically, 24% of patients had moderate to high synovial inflammation, which was significantly correlated with depressive symptoms, pain intensity, and self-reported anxiety.

Intravenous immunoglobulin as a therapy for autoimmune conditions.

Intravenous immunoglobulin (IVIg) is a medical preparation used as replacement therapy for patients with immunodeficiencies. Over time, IVIg's anti-inflammatory and immunomodulatory effects have been recognized, which have led to the approval of this therapy in the treatment of various pathologies, such as Kawasaki disease, immune thrombocytopenia, and Guillain-Barré syndrome. There are numerous studies in the literature regarding the off-label use of IVIg in the treatment of autoimmune diseases (e.

Acupuncture therapy in autoimmune diseases: A narrative review.

We provide a narrative review of experimental and clinical evidence for the effect of acupuncture in autoimmune diseases, based on randomized controlled studies, systematic review and meta-analyses, published between the years 2000-2023. Acupuncture in experimental models of rheumatoid arthritis (RA), multiple sclerosis, psoriasis, ulcerative colitis (UC) downregulated inflammatory cytokine expression, increased IL-10 expression, improved Treg cell differentiation, and also modulated macrophage polarization in RA and UC models. The anti-inflammatory effect of acupuncture in autoimmune disorders has been demonstrated to involve vagal-adrenal and cholinergic anti-inflammatory pathways.

The association between physical trauma and autoimmune articular and dermatological disorders.

Objective: This review investigates the association between physical trauma and the onset and progression of various inflammatory diseases, including psoriatic arthritis (PsA), rheumatoid arthritis (RA), spondyloarthropathies (SpA), and Familial Mediterranean Fever (FMF). In addition, we will refer to the linkage between physical injury and skin manifestations in patients with psoriasis, sarcoidosis and systemic sclerosis. The aim is to summarize the current evidence and explore the potential mechanisms through which trauma may affect these conditions.

IRF5 Controls Plasma Cell Generation and Antibody Production via Distinct Mechanisms Depending on the Antigenic Trigger.

Elevated levels of serum autoantibodies are a hallmark of systemic lupus erythematosus (SLE) and are produced by plasma cells in response to a variety of antigenic triggers. In SLE, the triggers are complex and may include both T cell-dependent/-independent and TLR-dependent/-independent mechanisms of immune activation, which ultimately contributes to the significant immune dysregulation seen in patients at the level of cytokine production and cellular activation (B cells, T cells, dendritic cells, neutrophils and macrophages). Interferon regulatory factor 5 (IRF5) has been identified as an autoimmune susceptibility gene and polymorphisms in IRF5 associate with altered expression and hyper-activation in distinct SLE immune cell subsets.

Artificial intelligence meets the world experts; updates and novel therapies in autoimmunity - The 14th international congress on autoimmunity 2024 (AUTO14), Ljubljana.

The bi-annual international congress on autoimmunity is a huge opportunity for the medical community to discuss the latest updates in the field. During the 14th congress 2024 (AUTO14) in Ljubljana, artificial intelligence (AI) occupied special attention due to its recent and ongoing unequivocal role in various medical fields including autoimmunity. For instance, through a challenging debate between world-experts and the most popular AI bot used (ChatGPT), several clinical cases including a case of vasculitis were discussed in the plenary sessions.

Conflicting interpretations and FDA reputation: the case of post-market surveillance of breast implants.

Conflicting interpretations regarding the severity of the adverse effects associated with FDA-approved drugs and therapies are common among the United States Food and Drug Administration (FDA), the medical community, patients, and the general public. However, scholars have paid little attention to how these conflicting interpretations may affect the FDA's reputation for facilitating inclusive dialogue between competing policy actors. Focusing on breast implants, a medical device characterized by a stormy regulatory past, we observe that the design properties of post-market surveillance are adjusted to low-quality information.

Factors associated with severity and mortality of COVID-19 in patients with connective tissue diseases and rheumatoid arthritis: A nation-wide, population-based analysis of the French national medico-administrative SNDS database.

Objectives: To investigate the risk and predictors of severity and mortality of COVID-19 infection in patients with Connective Tissue Diseases (CTDs).

Methods: Using the French nationwide claims and hospitalization database, we assembled a nation-wide exhaustive cohort of adult CTD patients with rheumatoid arthritis, systemic lupus, Sjögren's disease, inflammatory myopathies, systemic sclerosis. We analyzed the rates of hospitalization, severe inpatient stays (intensive care unit [ICU] admissions or in-hospital mortality), and in-hospital mortality with COVID-19 from January 1st to December 31st, 2020.

Rare copy number variant analysis in case-control studies using snp array data: a scalable and automated data analysis pipeline.

Background: Rare copy number variants (CNVs) significantly influence the human genome and may contribute to disease susceptibility. High-throughput SNP genotyping platforms provide data that can be used for CNV detection, but it requires the complex pipelining of bioinformatic tools. Here, we propose a flexible bioinformatic pipeline for rare CNV analysis from human SNP array data.

Systemic capillary leak syndrome.

The vascular endothelial barrier maintains intravascular volume and metabolic homeostasis. Although plasma fluids and proteins extravasate continuously from tissue microvasculature (capillaries, post-capillary venules), systemic vascular leakage increases in critical illness associated with sepsis, burns and trauma, among others, or in association with certain drugs or toxin exposures. Systemically dysregulated fluid homeostasis, which can lead to hypovolaemia, hypotensive shock and widespread tissue oedema, has been termed systemic capillary leak syndrome (SCLS) when overt secondary causes (for example, heart or liver failure) are excluded.