About 780,110 results

Pharmacological Inhibition of MALT1 Reverses Activation-Induced Metabolic Reprogramming and Ameliorates Autoimmune Pathogenesis in Multiple Animal Models of Chronic Inflammation
Subhabrata Biswas, Mya Steadman, Ynes Helou et. al.

Nov 9th, 2021 - Background/Purpose: Current therapies for autoimmune and inflammatory diseases generally target select disease nodes, often failing to produce durable clinical remission. Chronic inflammation is associated with alterations in immune cell metabolism, and it is possible that modulating metabolism may result in more durable responses. Mucosa-associated lymphoid tissue lymphoma translocation protei...

Epigenetic and Transcriptional Programs of CD4+ T Cell Anergy
Philip Titcombe, Milagros Silva Morales and Daniel Mueller, University of Minnesota et. al.

Nov 9th, 2021 - Background/Purpose: T cell tolerance is essential for preventing autoimmune diseases and resolving inflammation. To maintain tolerance, CD4+ T cells recognizing self-antigens in the periphery can exert active suppression as regulatory T cells (Treg) or enter an inactive state known as anergy. Recent evidence suggests that anergy occurs naturally within a subpopulation of polyclonal CD4+ T cells...

Therapeutic Drug Monitoring Compared to Standard Infliximab Therapy in Patients with Immune-mediated Inflammatory Diseases: A Randomized Controlled Trial
Silje Watterdal Syversen, Guro Goll, Kristin Jørgensen et. al.

Nov 9th, 2021 - Background/Purpose: Proactive therapeutic drug monitoring (TDM), a treatment strategy based on scheduled assessments of serum drug levels, has been proposed to optimize efficacy and safety of infliximab and other TNF inhibitors. It is still unclear whether proactive TDM improves clinical outcomes. The NOR-DRUM trials (A and B) are the first randomized trials to assess the impact of proactive TD...

Investigation of Antigen Specific CD4+ T Cells in Patients with Idiopathic Inflammatory Myopathies
Begum Horuluoglu, Angeles Shunashy Galindo-Feria, Karine Chemin et. al.

Nov 9th, 2021 - Background/Purpose: Idiopathic inflammatory myopathies (IIM) also known as myositis, are rare chronic autoimmune disorders represented by lesions in muscle, skin and lung. One of the most common autoantibodies in myositis, with a prevalence of 25-35%, is the anti Jo-1 autoantibodies, targeting the histidyl-transfer RNA synthetase (HisRS). The presence of autoantibodies in patients along with st...

Immune Responses to COVID-19 Vaccines in Patients Using Immunosuppressive Medication for Inflammatory Arthritis – An Observational Study of 1500 Patients
Ingrid Jyssum, Anne Therese Tveter, Fridtjof Lund-Johansen et. al.

Nov 9th, 2021 - Background/Purpose: To assess the strength and duration of the immunological response to COVID-19 vaccines in patients treated with immunosuppressive medication for inflammatory arthritis. Methods: Adult patients with a clinical diagnosis of rheumatoid arthritis (RA), spondyloartritis (SpA) or psoriatic arthritis (PsA) on treatment with any bDMARD, csDMARD, tsDMARD or prednisolone ( > 7,5 mg/da...

Autologous EBV-specific Cytotoxic T Cells in Systemic Lupus Erythematosus: An Innovative Phase I/IIa Clinical Trial
Antoine Enfrein, Beatrice Clemenceau, Soraya Saiagh et. al.

Nov 9th, 2021 - Background/Purpose: Epstein-Barr Virus (EBV) has been suggested as a potential environmental factor in systemic lupus erythematosus (SLE) onset and disease activity. Here, we report the results of a phase I/IIa clinical trial assessing the safety and the effects of anti-EBV CTL infusion in patients with non severe disease. Methods: Nine patients meeting the American College of Rheumatology (ACR...

Role of CD4+ T Cells in the Pathogenesis of RA: Immunization with Citrullinated T Cell Epitopes Is Sufficient to Induce Immunological and Clinical Manifestations of Arthritis in DR4-Transgenic Mice
Elena Tonti, Bhargavi Duvvuri, Sudeshna Dhar et. al.

Nov 9th, 2021 - Background/Purpose: Although the etiology of rheumatoid arthritis (RA) remains unclear, existing research suggests a complex interplay of both genetic and environmental factors. Citrullinated proteins/peptides, and immune responses to them, may lead to the breaching of immunological tolerance, and subsequent disease. While most research to date has focused on the specificity of anti-citrullinat...

Putting the Pieces on the Board: Mapping SLE Nephritis Biopsies from the Accelerating Medicines Project Using High-Density Immunofluorescence Imaging
Craig Smuda, Anna Eichinger, Robert Clancy et. al.

Nov 9th, 2021 - Background/Purpose: The Accelerating Medicines Project (AMP) has enabled significant increases in understanding of SLE nephritis pathology, providing a profile of dozens of leukocyte subsets within affected kidneys by single-cell RNA sequencing of nephritis biopsies. While these results suggest a complex network of interactions between cell populations during nephritis, the spatial positioning ...

Safety, Tolerability, Pharmacokinetics, Receptor Occupancy, and Suppression of T-cell-Dependent Antibody Response in a Phase 1 Study with KPL-404, an anti-CD40 Monoclonal Antibody
Manoj Samant, Alistair Wheeler, Guang-Liang Jiang et. al.

Nov 9th, 2021 - Background/Purpose: T-cell priming and T-cell-dependent B-cell responses require an intact cluster of differentiation (CD)40/CD40L pathway. CD40 is expressed on the surface of B-cells, dendritic cells, antigen-presenting cells, and non-immune cell types; its ligand, CD40L (CD154), is expressed on the surface of activated T-cells, platelets, and other cell types. Blockade of CD40/CD40L interacti...

Blood-based Immune Profiling Combined with Machine Learning Discriminates Psoriatic Arthritis from Psoriasis Patients
Michelle Mulder, Xuehui He, Juul van den Reek et. al.

Nov 9th, 2021 - Background/Purpose: Early detection of psoriatic arthritis (PsA) in psoriasis (Pso) patients is crucial for timely treatment and prevention of structural joint damage. We aimed to identify disease-specific immune profiles discriminating Pso from PsA patients, potentially facilitating adequate referral. Methods: The phenotype of PBMCs of consecutive Pso (N=45) and PsA (N=41) patients was determi...

Clinical Consequences of Hepatitis B Core Antibody Positivity After IVIG Administration
William West, Therese Posas-Mendoza, Jerald Zakem et. al.

Nov 9th, 2021 - Background/Purpose: Intravenous immunoglobulin (IVIG) is a blood product created by pooling of donor plasma that is used for a wide range of indications. IVIG is commonly used in the fields of neurology, rheumatology, hematology, and transplant medicine. Previous studies have identified transient positivity of hepatitis B core antibody (HBcAb) after receiving IVIG. This phenomenon signifies a p...

B Cell Intracellular IFNβ as a Unique Cellular Marker for the Development of Lupus Nephritis
Fatima Alduraibi, Huma Fatima, Winn Chatham et. al.

Nov 9th, 2021 - Background/Purpose: Our laboratory previously demonstrated a strong association of B cell intracellular interferon beta (IFNβ) with the development of anti-Smith/ribonuclear protein (Sm/RNP), anti-DNA, and lupus nephritis (LN) in African American (AA) systemic lupus erythematosus (SLE) patients. The objective of the present study is to determine if B cell IFNβ can be a unique SLE clinical progn...

Innate Immune Tolerance Attenuates Zymosan-Induced Arthritis, Inflammatory Gene Expression and Synovial Neutrophil Infiltration
Richard Bell, Chao Yang, Caroline Brauner et. al.

Nov 8th, 2021 - Background/Purpose: Zymosan (Zym) induces arthritis through TLR2- and Dectin-1-activated NK-κB signaling and inflammatory myeloid cell infiltration into the synovium of the injected joint. Innate immune tolerance after an initial TLR challenge dampens inflammatory responses induced by a second challenge. It is currently unknown if this innate immune tolerance affects Zym responses and can atten...

Manipulation of B7 Family Member Expression Demonstrates Synovial Macrophage Plasticity and Possible Future Targets for Treatment of Rheumatoid Arthritis
Annabelle Small, Katie Williams, Antonio Ferrante et. al.

Nov 8th, 2021 - Background/Purpose: Infiltration of monocyte-derived macrophages into the synovial tissue (ST) is a hallmark of rheumatoid arthritis (RA). These infiltrating cells lead to inflammation, local joint effusion, and joint damage via the production of inflammatory cytokines. Macrophages express an array of co-stimulatory receptors, particularly those of the B7 protein family, including the programme...

The Mechanistic Basis of anti-CD6 as a Novel Form for the Treatment of Autoimmune Diseases and Cancer
Mikel Gurrea-Rubio, Jeffrey Ruth, Qi Wu et. al.

Nov 8th, 2021 - Background/Purpose: The use of Immune Checkpoint Inhibitors (ICIs) is limited by the induction of immune-related adverse events. CD6 is expressed by most T lymphocytes and a subset of natural killer (NK) cells, and engages the ligands CD166/ALCAM and CD318. Interrupting CD6 interaction with its ligands using UMCD6 (anti-CD6) reverses autoimmunity in mouse models of rheumatoid arthritis, multipl...

Altered Metabolic Pathways in Synovial Fibroblasts of Individuals at Risk of Developing Rheumatoid Arthritis
Tineke de Jong, Simone Denis, Paul Tak et. al.

Nov 8th, 2021 - Background/Purpose: Cellular metabolism has been studied in fibroblast-like synoviocytes (FLS) of rheumatoid arthritis (RA) and osteoarthritis (OA) patients and raises the question whether observed metabolic alterations appear in response to chronic inflammation or whether primary changes in cellular metabolism might underlie disease pathogenesis. Previously, we showed that genes involved in li...

Abatacept and Other DMARDs Have Common Transcriptomic Effects on RA Synovial Tissue
Clément TRIAILLE, Tatiana SOKOLOVA, Gaëlle TILMAN et. al.

Nov 8th, 2021 - Background/Purpose: Our goal was to assess histological and transcriptomic effects of Abatacept (ABA) on RA synovium, and to compare them with previously published data obtained by our group using the same study design on other DMARDs: Tocilizumab (TCZ), Rituximab (RTX), Methotrexate (MTX) and Adalimumab (ADA). Methods: Synovial tissue was obtained using ultrasound-guided biopsy from affected j...

SARS-CoV-2 Antibody Phenotype and Immune Gene Expression in Multi-system Inflammatory Syndrome in Children
Kate Webb, Thandeka Moyo-Gwete, Simon Mendelsohn et. al.

Nov 8th, 2021 - Background/Purpose: Multi-system Inflammatory Syndrome in Children (MIS-C) is a severe disease that affects a small proportion of children exposed to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Differences in SARS-CoV-2 antibody responses and immune gene expression between SARS-CoV-2-infected children who develop MIS-C and those who do not may provide insight into the mechanis...

Low CD39 Expression on B Cells Predicts the Occurrence of Anti-Drug Antibodies in RA Patients Treated with Rituximab
Samuel Bitoun, Bineta Ly, Signe Hässler et. al.

Nov 8th, 2021 - Background/Purpose: Anti-Drug antibodies (ADAb) are well studied and have an impact on response to treatment with monoclonal anti-TNF biologics. Rituximab treatment has an important immunogenic potential as it is a chimeric antibody. Most recent studies on biosimilars have identified low rates of ADAb among rituximab-treated patients without impact on treatment efficacy. The lack of sensitivity...

Proteomic Profiling of MIS-C Patients Reveals Heterogeneity Relating to Interferon Gamma Dysregulation and Vascular Endothelial Dysfunction
Caroline Diorio, Rawan Shraim, Laura Vella et. al.

Nov 7th, 2021 - Background/Purpose: Multi-system Inflammatory Syndrome in Children (MIS-C) is a major complication of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic in pediatric patients. Children with MIS-C present with varying degrees of cardiovascular and hyperinflammatory symptoms. We performed a comprehensive analysis of the plasma proteome of more than 1400 proteins in children...