[Long-term follow up of efficiency and safety of CD19-CAR T-cell treatment of systemic lupus erythematosus].

Background: Chimeric antigen receptor T-cells (CAR T-cells) are an effective therapeutic approach in the treatment of B-cell driven malignancies. In addition to malignant B-cells, autoreactive B-cells are important targets for CD19 CAR T-cells, as they are a source of autoantibody production and support both the onset and progression of systemic lupus erythematosus (SLE). We and others have shown that their use in severe and therapy-refractory cases of SLE is effective and, moreover, safe.

CD45 and CD148 Are Critically Involved in Neutrophil Recruitment and Function During Inflammatory Arthritis in Mice.

Neutrophils play a key role in autoimmune diseases like rheumatoid arthritis, contributing to tissue damage through rapid recruitment and activation. In this study, we investigated the regulatory properties of two receptor-like tyrosine phosphatases (RPTPs), CD45 and CD148, in inflammatory arthritis. Using an in vivo mouse model of K/BxN serum transfer-induced arthritis, we found that CD45 and CD148 feature distinct regulatory properties during inflammatory arthritis.

Individual subsets of alternatively-activated macrophages differentially contribute to tissue repair and the resolution of inflammation.

Although alternatively-activated macrophages (AAM) have been implicated in the resolution of inflammation and tissue repair, their exact role, heterogeneity and origin in vivo remain incompletely defined. Here we show that distinct subsets of macrophages can acquire alternatively activated phenotypes in response to tissue injury where these cellular subsets display contrasting spatiotemporal dynamics and differentially contribute to the resolution of inflammation and tissue repair. By studying a model of cardiotoxin-induced muscle injury, we identify a population of monocyte-derived AAM characterized by expression of arginase-1 (Arg-1) and triggering receptor expressed on myeloid cells 2 (Trem2) that emerged in response to injury and fostered clearance of dying neutrophils and necrotic myofibers as well as the subsequent resolution of inflammation.

Neutrophil Heterogeneity Identifies an Association of LAMP1 With Proliferative Lupus Nephritis.

Lupus nephritis (LN) is a severe manifestation of systemic lupus erythematosus (SLE) with limited biomarkers for early detection. While neutrophils contribute to SLE pathogenesis, their phenotypic heterogeneity in disease remains poorly characterized. Here, we used mass cytometry to profile blood neutrophils from patients with biopsy-confirmed proliferative LN and healthy controls.

A multidimensional analysis of temporomandibular joint and ankle joint erosion in inflammatory arthritis.

Rheumatoid arthritis (RA) and other inflammatory arthritis are systemic diseases that primarily affect the joints, characterized by synovial inflammation and progressive cartilage and bone degradation. The temporomandibular joint (TMJ) is reported to be involved in over 50% of RA cases, often leading to severe jaw pain and compromised oral function. Despite its prevalence, TMJ involvement is often underestimated, and its cellular and molecular mechanisms remain poorly understood.

Loss of myeloperoxidase aggravates skin and joint inflammation in the mannan-induced psoriatic arthritis mouse model.

Psoriasis is a systemic inflammatory skin disorder with a prevalence of 2 % in adults. Up to 30 % of affected individuals further develop psoriatic arthritis (PsA), which is characterized by additional joint inflammation. Myeloperoxidase (MPO) is strongly expressed by neutrophils and, to a lesser extent, also by other myeloid cells.

Hand Function Impairments Are More Pronounced in Female RA and PsA Patients and also Found in Patients without Concurrent Hand Inflammation.

Purpose: Hand function is considered being critical in rheumatoid (RA) and psoriatic arthritis (PsA) patients, however, comprehensive assessment of hand function is rarely done in patients with inflammatory arthritis.

Methods: In this cross-sectional study, RA and PsA patients and healthy controls (HC) were assessed for hand function using isometric grip strength (dynamometer), dynamic grip strength (vigorimeter), and fine-motor skills (Moberg Picking-Up Test). Between-group differences and the associations with disease activity (Disease Activity Score 28, DAS28, RA; Disease Activity in Psoriasis Arthritis, DAPSA, PsA) were analysed using linear mixed-effects models with age as covariate and participants ID as random intercept term.

Chimeric antigen receptor T cells in treatment-refractory DAGLA antibody-associated encephalitis.

Background: Autoimmune encephalitides are a heterogeneous group of autoantibody-associated central nervous system disorders. The clinical course of autoimmune encephalitides can be life threatening, and treatment can be challenging.

Objective: This report describes a case of treatment-refractory, anti-diacylglycerol lipase alpha (DAGLA) antibody-associated autoimmune encephalitis successfully treated with chimeric antigen receptor (CAR) T cells.

Differential molecular signatures in response to CD19-CAR T cell therapy compared with conventional pharmacotherapy in systemic lupus erythematosus.

Objectives: Early trials of CD19-chimeric antigen receptor (CAR) T cell therapy in systemic lupus erythematosus (SLE) show promise, but the molecular mechanisms underlying its disease-modifying effects remain unclear. We aimed to compare biological profiles and alterations following CD19-CAR T cell versus standard pharmacotherapy in SLE.

Methods: Pseudo-bulk gene expression derived from single-cell RNA sequencing of peripheral blood mononuclear cells from 7 SLE patients before and after CD19-CAR T cell therapy was compared with whole-blood transcriptome data from 30 SLE patients in remission on standard pharmacotherapy and 31 SLE patients before and 6 months after treatment with rituximab, belimumab, or cyclophosphamide.

The risk of femoral fracture is increased in patients with ischemic stroke and transient ischemic attack-a population-based observational secondary analysis of the Austrian stroke cohort.

Background: An increased risk of femoral fractures after ischemic stroke (IS) and transient ischemic attack (TIA) has been shown previously. However, it remains unclear whether the ischemic cerebral event is directly associated with the risk of femoral fractures.

Aims: The aim of this study was (1) to assess the association between the frequency of femoral fractures in patient with IS and TIA, and (2) to compare the risk of femoral fractures to the Austrian general population.

Effects of different B-cell-depleting strategies on the lymphatic tissue.

Objectives: To assess the efficacy of new protein-based B cell depletion with glyco-engineered anti-CD20 antibody obinutuzumab (OBI) and the CD19/CD3 T cell engager blinatumomab (BLI) in patients with autoimmune diseases (AIDs) in comparison to rituximab (RTX) and CD19 chimeric antigen receptor (CAR) T cell therapy.

Methods: Sequential inguinal lymph node biopsies were taken before and after treatment with OBI-, BLI-, RTX- and CD19-CAR T cells in patients with AID. CD19+ and CD20+ B cells, plasma cells, T cells and macrophages were analysed by immunohistochemistry.

Gut-specific histamine 3 receptor signaling orchestrates microglia-dependent resolution of peripheral inflammation.

Chronic inflammatory diseases, like rheumatoid arthritis (RA) have been described to cause central nervous system (CNS) activation. Less is known about environmental factors that enable the CNS to suppress peripheral inflammation in RA. Here, we identified gut microbiota-derived histamine as such factor.

A robust machine learning approach to predicting remission and stratifying risk in rheumatoid arthritis patients treated with bDMARDs.

Rheumatoid arthritis (RA) is a chronic autoimmune disease affecting millions worldwide, leading to inflammation, joint damage, and reduced quality of life. Although biological disease-modifying antirheumatic drugs (bDMARDs) are effective, they are costly, and up to 40% of patients do not achieve remission within six months. Accurate prediction of treatment response is crucial for optimizing care, minimizing side effects, and enhancing cost efficiency.

Spatially informed phenotyping by cyclic-in-situ-hybridisation identifies novel fibroblast populations and their pathogenic niches in systemic sclerosis.

Objectives: Spatially nonresolved transcriptomic data identified several functionally distinct populations of fibroblasts in health and disease. However, in-depth transcriptional profiling in situ at the single-cell resolution has not been possible so far. We thus aimed to profile these populations by single-cell spatial transcriptomics using cyclic in situ hybridisation (cISH).

[CAR T cells in non-malignant diseases].

Background: Chimeric antigen receptor (CAR) T cells specific for CD19 or B cell maturation antigen (BCMA) are now the standard treatment for relapsed/refractory B cell neoplasms. Because autoreactive B cells play a key role in the pathogenesis of autoimmune diseases (AID), it has been hypothesized that B cell-specific CAR-T cells eliminate autoreactive B cell clones via a deep depletion of B cells and lead to a reset of the immune system. Initial pilot studies with CAR T cells against CD19 in rheumatologic and neurologic AIDs have confirmed this hypothesis and led to sustained drug-free remission of the diseases.

Matrix stiffness regulates profibrotic fibroblast differentiation and fibrotic niche activation in systemic sclerosis.

Objectives: Fibrosis progression in systemic sclerosis (SSc) has been attributed to matrix stiffness. Despite extensive research on fibroblast heterogeneity and subset imbalances in fibrotic disorders, the interplay between biomechanical cues and fibroblast dynamics remains largely unexplored. Here, we investigate how matrix stiffness alters fibroblast transcriptional state and influences lineage specification in fibrotic skin.

Disease-associated brain activation predicts clinical response to TNF inhibition in rheumatoid arthritis (PreCePra): a randomised, multicentre, double-blind, placebo-controlled phase 3 study.

Background: Rheumatoid arthritis is an inflammatory disease frequently treated with TNF inhibitors. Little is known about predictors of response to TNF inhibitors. Because clinical response in rheumatoid arthritis is measured by composite scores containing subjective patient-orientated domains (eg, pain and global disease perception), we hypothesised that patients with high disease representation in the CNS might respond better to TNF inhibitors than patients with less CNS disease representation.

Corrigendum: Advancement and independent validation of a deep learning-based tool for automated scoring of nail psoriasis severity using the modified nail psoriasis severity index.

[This corrects the article DOI: 10.3389/fmed.2025.

Comparison of the safety profiles of CD19-targeting CAR T-cell therapy in patients with SLE and B-cell lymphoma.

CD19-directed chimeric antigen receptor (CAR) T-cell therapy has revolutionized the treatment of relapsed/refractory B-cell non-Hodgkin lymphoma (B-NHL) and recently showed effects in autoimmune diseases, such as systemic lupus erythematosus (SLE). Despite high levels of inflammation, toxicity seemed to differ between patients with SLE and B-NHL. We therefore compared the CAR T-cell kinetics and treatment-related side effects to better define the toxicity profiles.

Role of Chimeric Antigen Receptor-Expressing Cell Therapy in Immune-Mediated Kidney Diseases: A Review.

Immune-mediated kidney diseases are characterized by an adaptive immune response directed against various self-antigens. B cells, as progenitors of autoantibody-producing plasma cells and as antigen-presenting cells, play a crucial role in the pathogenesis of these diseases. Despite significant advancements in B-cell-targeting therapies, relapses are common among patients.

Improving preventive health in inflammatory rheumatic diseases: A randomized controlled trial of an educational video intervention.

Objective: To evaluate the impact of an educational video on adherence to preventive health measures in patients with inflammatory rheumatic diseases.

Methods: The KOMO-R study was a prospective, six-month, single-center, randomized controlled trial. Participants received personalized to-do lists with up to 13 tasks based on local preventive health guidelines.

Advances in precision medicine in imaging and therapeutic strategies for psoriatic disease.

Psoriatic disease, encompassing psoriasis (PsO) and psoriatic arthritis (PsA), affects approximately 2 % of the global population. In the majority of cases, skin alterations occur first, followed by musculoskeletal disorders. The transition from cutaneous to synovio-entheseal disease reflects a gradual immune-driven progression from localized to systemic manifestations in most cases.

Models of Rheumatoid Arthritis.

Mice models induced by immunization are used to study rheumatoid arthritis (RA) and its molecular mechanisms. In this article, we describe three models that mimic the clinical symptoms of human RA and can be applied to genetically modified mice. The collagen-induced arthritis (CIA), K/BxN serum-induced arthritis (SIA), and antigen-induced arthritis (AIA) models will be presented.