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Publications (1,005)
Objective
To investigate how the mucosal barrier in the intestine influences the development of arthritis, considering that metabolic changes in the intestinal epithelium influence its barrier function.
Methods
Intestinal hypoxia inducible factor (HIF)-2α expression was assessed before, at onset and during experimental arthritis and human rheumato...
Background
While a so-called gut-joint axis is supported by many clinical observations, the current knowledge on such axis is mostly confined to descriptive and correlative data, e.g. showing the microbiota changes are associated with arthritis. In contrast, mechanistic data on how molecular changes in the intestinal epithelium influence the develo...
Innate lymphoid cells (ILC) not only are responsible for shaping the innate immune response but also actively modulate T cell responses. However, the molecular processes regulating ILC-T cell interaction are not yet completely understood. The protein butyrophilin 2a2 (Btn2a2), a co-stimulatory molecule first identified on antigen-presenting cells,...
Objective: The objective of this study was to compare the impact of psoriatic disease (psoriatic arthritis [PsA] and psoriasis) and rheumatoid arthritis (RA) on objective and subjective parameters of hand function.
Methods: Hand function was determined in this cross-sectional study by 1) vigorimetric grip strength, 2) the Moberg Picking-Up Test us...
Enthesitis is a key feature of several different rheumatic diseases. Its pathophysiology is only partially known due to the lack of access to human tissue and the shortage of solid animal models for enthesitis. Here we aimed to develop a model, which mimics the effector phase of enthesitis and reliably leads to inflammation and new bone formation....
Group 2 innate lymphoid cells (ILC2s) were detected in the peripheral blood and the joints of rheumatoid arthritis (RA) patients, serum-induced arthritis (SIA), and collagen-induced arthritis (CIA) using flow cytometry. Circulating ILC2s were significantly increased in RA patients compared with healthy controls and inversely correlated with disease...
Chronic inflammatory diseases are associated with bone loss. While the occurrence of systemic bone loss is well described in chronic inflammatory diseases, the impact of these conditions on articular bone has not been systematically investigated. Recent refinements in high-resolution CT assessment of the joints now allow the accurate measure of art...
NR4A1 (Nur77 or NGFI‐B), an orphan member of the nuclear receptor superfamily, has been identified as a key regulator of the differentiation and function of myeloid, lymphoid and mesenchymal cells. The detailed role of NR4A1 in bone biology is incompletely understood. Here we report a role for NR4A1 as novel factor controlling the migration and rec...
Background
Pain is one of the most important domains affecting health-related quality of life (HRQoL) in patients with psoriatic arthritis (PsA). Secukinumab has demonstrated rapid and sustained improvements in signs and symptoms, including HRQoL, among patients with active PsA. This analysis evaluates the effect of secukinumab on patient-reported...
Objective
The Psoriatic Arthritis Long-term Assessment of Clinical Efficacy (PALACE) clinical trial programme findings demonstrated that apremilast, an oral phosphodiesterase 4 inhibitor, is effective for treating psoriatic arthritis (PsA). Enthesitis and dactylitis are difficult-to-treat features of PsA leading to disability and affecting quality...
Background:
ADAMTS aggrecanases play a major role in cartilage degeneration during degenerative and inflammatory arthritis. The cartilage-specific secreted protein Upper zone of growth plate and cartilage matrix associated protein (Ucma) has been shown to block ADAMTS-triggered aggrecanolysis in experimental osteoarthritis. Here we aimed to invest...
Background:
Rheumatoid arthritis (RA) preferentially affects women, with the peak incidence coinciding with estrogen decrease in menopause. Estrogen (E2) may therefore have intrinsic immune-regulatory properties that vanish with menopause. Fc sialylation is a crucial factor determining the inflammatory effector function of antibodies. We therefore...
Systemic lupus erythematosus (SLE) is characterized by autoimmune reactivity against components of the cell's nucleus arising after insufficient removal of dead cells. We used a lupus mouse model induced by the cytotoxic alkane oil pristane to elucidate the impact of ROS on SLE. Pristane-induced lupus was strongly exacerbated in NOX2-deficient (Ncf...
The production of reactive oxygen species (ROS) via the oxidative burst has been connected with promotion of inflammation and tissue damage, but in recent years has been implicated in regulation and resolution of inflammation.
The aim of this project was to elucidate the impact of the oxidative burst on the development of lupus-like autoimmunity. L...
Immunoglobulin G (IgG) harbors a conserved N-glycosylation site which is important for its effector functions. Changes in glycosylation of IgG occur in many autoimmune diseases but also in physiological conditions. Therefore, the glycosylation pattern of serum IgG is well characterized. However, limited data is available on the glycosylation patter...
Introduction
In the Western society, obesity and the resulting metabolic changes are an increasing field of medical research. Both conditions alter the expression of adipokines such as adiponectin, visfatin or leptin, which can modulate key pathways of the immune system or the progress of osteoarthritis (OA).
Objectives
To evaluate cross-linking i...
Objectives
Bone loss is a well-established consequence of rheumatoid arthritis (RA). To date, bone disease in RA is exclusively characterised by bone density measurements, while the functional properties of bone in RA are undefined. This study aimed to define the impact of RA on the functional properties of bone, such as failure load and stiffness....
Eosinophils were reported to serve as an essential component of the plasma cell niche within the bone marrow. As the potential contribution of eosinophils to humoral immunity has remained incompletely understood, we aimed to further characterize their role during antibody responses and to additionally investigate their role in autoimmune disease. C...
The anti-citrullinated protein antibody (ACPA) response dynamically evolves before the onset of rheumatoid arthritis (RA)
HLA-shared epitope alleles and T cells are suggested to be involved in driving the expansion of the ACPA response in the pre-arthritis phase of RA
ACPA-IgG molecules are extensively glycosylated in the variable domain because of...
Background
The anti-inflammatory effect of abatacept is most pronounced in patients with high-titer autoantibodies (including anticitrullinated protein antibodies [ACPA] and rheumatoid factor [RF]). Considering that autoantibodies trigger inflammatory cytokine production by monocytes and that abatacept binds to monocytes, influencing their function...
Objectives
The enzyme poly(ADP-ribose) polymerase-1 (PARP-1) transfers negatively charged ADP-ribose units to target proteins. This modification can have pronounced regulatory effects on target proteins. Recent studies showed that PARP-1 can poly(ADP-ribosyl)ate (PARylate) Smad proteins. However, the role of PARP-1 in the pathogenesis of systemic s...
Hypoxia-inducible factors (HIFs) are key elements for controlling immune cell metabolism and functions. While HIFs are known to be involved in T cells and macrophages activation, their functions in B lymphocytes are poorly defined. Here, we show that hypoxia-inducible factor-1α (HIF-1α) contributes to IL-10 production by B cells. HIF-1α regulates I...
Innate lymphoid cells (ILC) have a high potency for cytokine production independent of specific Ag stimulation. Imbalance of ILC subsets may influence cytokine production in humans and hence be associated with the development of inflammatory disease. Evidence for an imbalance of ILC homeostasis in human disease, however, is very limited to date. In...
Objectives
Stimulators of soluble guanylate cyclase (sGC) are currently investigated in clinical trials for the treatment of fibrosis in systemic sclerosis (SSc). In this study, we aim to investigate the role of protein kinases G (PKG) as downstream mediators of sGC–cyclic guanosine monophosphate (cGMP) in SSc.
Methods
Mice with combined knockout...
Microbial metabolites are known to modulate immune responses of the host. The main metabolites derived from microbial fermentation of dietary fibers in the intestine, short-chain fatty acids (SCFA), affect local and systemic immune functions. Here we show that SCFA are regulators of osteoclast metabolism and bone mass in vivo. Treatment of mice wit...
Objectives
Systemic sclerosis (SSc) fibroblasts remain activated even in the absence of exogenous stimuli. Epigenetic alterations are thought to play a role for this endogenous activation. Trimethylation of histone H3 on lysine 27 (H3K27me3) is regulated by Jumonji domain-containing protein 3 (JMJD3) and ubiquitously transcribed tetratricopeptide r...
Advances in treatments and treatment strategies for PsA have led to many patients responding well to management of their disease, and targeting remission as a treatment goal is now a possibility. Treat to target is a strategy aimed at maximizing benefit, irrespective of the type of medication used, by monitoring disease activity and using it to gui...
Background
Tumor necrosis factor inhibitors (TNFi) signify a major advance in the treatment of rheumatoid arthritis (RA). However, treatment success initially remains uncertain as one third of patients do not respond adequately to TNFi.
Objectives
We investigated whether brain activity associated to arthritis measured by functional magnetic resona...
Background
Psoriatic arthritis (PsA) is an immune-mediated chronic inflammatory arthropathy-associated with psoriasis. T helper 17 pathway has been shown to play an important role in PsA.
Objectives
In this study, we aimed to investigate concentrations of TH17 pathway cytokines such as IL-17, IL-22 and IL-23 in psoriasis (PsO) with/and without str...
Background
GiACTA, a randomized, double-blind, placebo-controlled trial, evaluated the efficacy and safety of tocilizumab (TCZ), an IL-6 receptor-α inhibitor, in patients with giant cell arteritis (GCA).1,2
Objectives
Secondary analyses to evaluate the differential efficacy and safety of TCZ between patients with new-onset and relapsing GCA and to...
Background
Secukinumab, an anti-interleukin 17A monoclonal antibody, showed significant improvement of signs and symptoms of psoriatic arthritis (PsA) in FUTURE 1 study. Available studies used conventional radiography, not allowing a deeper imaging analysis of the inflammatory changes during application.
Objectives
To assess short term efficacy of...
Background
Musculoskeletal symptoms are considered as one of the most frequent extra-intestinal manifestation in Inflammatory Bowel Disease (IBD) patients with a prevalence of up to 40% involving axial and/or peripheral joints. Data on the prevalence of musculoskeletal disease, in particular of SpA are limited and vary considerably due to different...
Background
Achieving remission is the ultimate treatment goal in patients with rheumatoid arthritis (RA). With the development and wider use of highly effective disease modifying anti-rheumatic drugs (DMARD) about half of RA patients reach the disease remission state (1), raising the question about tapering or stopping anti-rheumatic treatment and...
Background
Obesity and hyperinsulinemia are of increasing importance in the Western society. Both obesity and insulin resistance lead to changes in expression of adipokines such as adiponectin, visfatin or leptin, which appear to be immunomodulatory factors also in rheumatic diseases.
Objectives
Since osteoarthritis (OA) is often accompanied by hy...
Background
IL-23 is considered to play an important role in the development of enthesitis. Ustekinumab (UST), a combined inhibitor of IL-12/IL-23 shows efficacy in psoriatic arthritis (PsA), which is driven by enthesial and synovial disease, while it has no therapeutic role in diseases driven by synovitis alone, such as rheumatoid arthritis. We the...
Background
The anti-inflammatory effect of abatacept (CTLA4-Ig) is most pronounced in patients with high-titer autoantibodies (including anti-citrullinated protein antibodies, ACPA, and rheumatoid factor, RF) even exceeding the effect of TNF inhibitors (TNFi)¹. Considering that autoantibodies trigger inflammatory cytokine production by monocytes² a...
Background
Rheumatoid arthritis preferentially affects women. RA has its peak over 50 years coincidencing with the decrease in sex hormones in menopause. Recently, the transition from asymptomatic autoimmunity to RA has been shown to essentially depend on the glycosylation status of antibodies affecting the binding affinity to Fc gamma receptors¹....
Background
Apremilast (APR), an oral phosphodiesterase 4 inhibitor, regulates immune activity in psoriatic arthritis (PsA) patients. Safety data were pooled from the phase 3 PALACE 1, 2, and 3 studies.
Objectives
Evaluate the long-term safety of APR treatment for up to 4 years in patients with active PsA despite prior conventional DMARDs and/or bi...
Background
Tumor necrosis factor inhibitors (TNFi) are the most frequently used bDMARDs in RA patients. TNFi induces remission in a substantial numbers of patients. Once remission, particularly sustained remission is achieved the question arises whether TNFi can be successfully tapered. To date biomarkers, which can help to predict if TNFi can be t...
Background
Bone damage in rheumatoid arthritis (RA) typically emerges at certain anatomical hotspots corresponding to the so-called “bare area”, an intra-articular region between the cartilage and the insertion site of the joint capsule (1,2). We hypothesized that this region exhibits certain micro-anatomical properties, which facilitates the emerg...
Background
Due to an increasing number and an earlier use of effective disease modifying anti-rheumatic drug (DMARD) therapy a growing number of rheumatoid arthritis (RA) patients reaches a state of clinical remission of disease. Whether clinical remission completely protects from structural bone damage, however, is still a matter of debate as conv...
Background
Bone erosion is a hallmark of inflammatory joint diseases. Its meticulous detection is highly important for correct diagnosis and monitoring of therapy response. Earlier studies showed that musculoskeletal ultrasound (MSUS) has a higher sensitivity than conventional radiography with regards to detection of bone erosions (1) making MSUS m...
Background
Optimizing treatment choice in psoriatic arthritis (PsA) necessitates an understanding of the long-term effects of therapies across varied manifestations of this complex disease. Data from 4 years of apremilast (APR) treatment in PALACE 1 were used to examine disease control across markers of active inflammation, such as SJC, as well as...
Background
Systemic bone loss is a well-known and severe consequence in axial spondyloarthritis (axSpA). To date deterioration of bone microstructure has only been described in patients with long-standing ankylosing spondylitis while bone microstructure has not been assessed in axSpA.
Objectives
The aim of the present study was to investigate bone...
Background
Dactylitis and enthesitis, hallmark features of psoriatic arthritis (PsA), may be difficult to manage. PALACE 1, 2, and 3 compared the efficacy and safety of apremilast (APR) with placebo (PBO) in patients (pts) with active PsA despite prior conventional DMARDs and/or biologics.
Objectives
Report the impact of long-term APR 30 mg BID (A...
Background
People at risk of developing rheumatoid arthritis (RA) may be candidates for interventions aimed at preventing RA development [1]. The identification of such “at risk” populations includes testing for genetic and other (e.g. autoantibody) biomarkers. However, little is known about the people's perspectives on these tests, how they react...
Background
Pain remains a major clinical challenge in the treatment of psoriatic arthritis (PsA). Secukinumab (SEC) has demonstrated significant efficacy in PsA patients (pts), across a range of quality of life related outcome measures.1,2
Objectives
This post-hoc analysis evaluated change in pain scores from baseline (BL) to Week (Wk) 104 in PsA...
Background
Chronic and exaggerated fibroblast activation is a central hallmark of Systemic Sclerosis (SSc) fibrotic disease and results in a high morbidity and mortality. Epigenetic changes might play important roles in mediating chronic fibroblast activation. Trimethylation of H3 at lysine residue K27 (H3K27me3) is a repressive epigenetic mark tha...
Background
Baricitinib (BARI), an oral inhibitor of Janus kinase (JAK) 1 and JAK 2, is being developed for the treatment of rheumatoid arthritis (RA). RA-BEGIN was a phase 3 double-blind, three-arm multicentre study of BARI administered as monotherapy or in combination with methotrexate (MTX) to patients (pts) with early active RA who had no or lim...
Background
Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by bone, cartilage and muscle loss. While bone and cartilage damage have been extensively studied in the past, the effects of RA on volume and composition of hand muscles have not yet been studied. This situation is surprising, since visible hand muscle atrophy is...
Background
Rheumatoid arthritis is a chronic form of inflammatory arthritis that is thought to have an early stage or reversibility with effective therapy (“window of opportunity”).
Objectives
In the present study, we explored the effects of induction therapy with anti-TNFα antibody infliximab (IFX) plus methotrexate (MTX) compared with MTX alone...
Many effector mechanisms of neutrophils have been implicated in the pathogenesis of systemic lupus erythematosus (SLE). Neutrophil extracellular traps (NETs) have been assigned a particularly detrimental role. Here we investigated the functional impact of neutrophils and NETs on a mouse model of lupus triggered by intraperitoneal injection of the c...
The goal of this study was to investigate the glycosylation profile of native IgG present in serum immune complexes in patients with rheumatoid arthritis (RA). To accomplish this, lectin binding assays, detecting the accessibility of glycans present on IgG-containing immune complexes by biotinylated lectins were employed. Lectins capturing fucosyl...
Fibrotic tissue remodelling and vascular alterations cause high morbidity and mortality in patients with systemic sclerosis (SSc).1 2 While the pathogenesis of SSc is only partially understood, recent evidence demonstrates a fundamental role of hedgehog signalling in fibrotic disease manifestations. Hedgehog signalling is activated in fibrotic SSc...
Objective:
To characterize the specific structural properties of the erosion-prone bare area of the human joint and to search for early microstructural changes in this region during rheumatoid arthritis Methods: An initial cadaveric study was used for exact localization of the bare area of the metacarpal heads, detection of cortical micro-channels...
Objectives:
Janus kinase 2 (JAK2) has recently been described as a novel downstream mediator of the pro-fibrotic effects of transforming growth factor-β. Although JAK2 inhibitors are in clinical use for myelodysplastic syndromes, patients often rapidly develop resistance. Tumour cells can escape the therapeutic effects of selective JAK2 inhibitors...
Periarticular bone loss is a long known but yet insufficiently understood phenomenon in patients with rheumatoid arthritis. This study investigated whether autoimmunity against citrullinated proteins is causally involved in triggering periarticular bone loss. Periarticular bone loss was studied in the standard antigen induced arthritis (AIA) mouse...
Microglia cells fulfill key homeostatic functions and essentially contribute to host defense within the CNS. Altered activation of microglia, in turn, has been implicated in neuroinflammatory and neurodegenerative diseases. In this study, we identify the nuclear receptor (NR) Nr4a1 as key rheostat controlling the activation threshold and polarizati...
Importance:
Accumulating evidence links inflammation and atrial fibrillation (AF).
Objective:
To assess whether markers of systemic and atrial inflammation are associated with incident AF in the general population.
Design, setting, and participants:
The Bruneck Study is a prospective, population-based cohort study with a 20-year follow-up (n?=...
Activation of proinflammatory macrophages is associated with the inflammatory state of rheumatoid arthritis. Their polarization and activation are controlled by transcription factors such as NF-κB and the AP-1 transcription factor member c-Fos. Surprisingly, little is known about the role of the AP-1 transcription factor c-Jun in macrophage activat...
Bone remodeling is a continuous process to retain the structural integrity and function of the skeleton. A tight coupling is maintained between osteoclast-mediated resorption of old or damaged bones and osteoblast-mediated formation of new bones for bone homeostasis. While osteoblasts differentiate from mesenchymal stem cells, osteoclasts are hemat...