A5001884060- Rheumatoid Arthritis Research and Therapies
- Monoclonal and Polyclonal Antibodies Research
- Cell Adhesion Molecules Research
- Advanced Glycation End Products research
- Systemic Lupus Erythematosus Research
- Immune Response and Inflammation
- HER2/EGFR in Cancer Research
- Bone Metabolism and Diseases
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Inflammatory mediators and NSAID effects
- Bone health and treatments
- Immunotherapy and Immune Responses
- Radiopharmaceutical Chemistry and Applications
- T-cell and B-cell Immunology
- Cytokine Signaling Pathways and Interactions
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Protease and Inhibitor Mechanisms
- Extracellular vesicles in disease
- Alcohol Consumption and Health Effects
- S100 Proteins and Annexins
- Connective tissue disorders research
- Immunodeficiency and Autoimmune Disorders
- Fatty Acid Research and Health
- Cell Image Analysis Techniques
- Nanoplatforms for cancer theranostics
Karolinska Institutet
2015-2024
Karolinska University Hospital
2011-2023
Center for Rheumatology
2018
Swedish Rheumatism Association
2006
Significance High-mobility group box (HMGB)1 is a nuclear protein that we have identified as proinflammatory mediator during infection or sterile tissue injury, which importantly orchestrates the innate immune responses. The mechanisms of HMGB1 release require translocation from nucleus to cytoplasm and into extracellular space. We recently reported inflammasome PKR mediates cytoplasm, but mechanism was previously unknown. Here, describe our discovery JAK/STAT1 required for LPS-...
Rheumatoid arthritis (RA)-specific anti-citrullinated protein/peptide antibodies (ACPAs) appear before disease onset and are associated with bone destruction. We aimed to dissect the role of ACPAs in osteoclast (OC) activation identify key cellular mediators this process.Polyclonal ACPA were isolated from synovial fluid (SF) peripheral blood patients RA. Monoclonal single SF B-cells OCs developed cell precursors or without ACPAs. analysed expression citrullinated targets peptidylarginine...
The nuclear protein HMGB1 has previously been demonstrated to act as an alarmin and promote inflammation upon extracellular release, yet its mode of action is still not well defined. Access highly purified preparations from prokaryotic eukaryotic sources enabled studies activation human PBMC or synovial fibroblast cultures in response alone after binding cofactors. on own could induce detectable IL-6 production. However, strong enhancing effects induction proinflammatory cytokine production...
Neutrophil extracellular traps containing citrullinated peptides promote inflammation in synovial fibroblasts.
Abstract Introduction In addition to its direct proinflammatory activity, extracellular high mobility group box protein 1 (HMGB1) can strongly enhance the cytokine response evoked by other molecules, such as lipopolysaccharide (LPS), CpG-DNA and IL-1β, through formation of complexes. Extracellular HMGB1 is abundant in arthritic joint tissue where it suggested promote inflammation intra-articular injections induce synovitis mice neutralizing therapy suppresses development experimental...
Rheumatoid arthritis (RA)-specific anti-citrullinated protein/peptide antibodies (ACPAs) might contribute to bone loss and arthralgia before the onset of joint inflammation. We aimed dissect additional mechanisms by which ACPAs development pathology.Fibroblast-like synoviocytes (FLS) were isolated from synovial membrane patients with RA. The FLS cultures stimulated polyclonal (anti-CCP-2 antibodies) purified peripheral blood RA or monoclonal derived single fluid B cells. analysed how...
The lung is implicated as a site for breach of tolerance prior to onset seropositive rheumatoid arthritis (RA). To substantiate this, we investigated lung-resident B cells in bronchoalveolar lavage (BAL) samples from untreated early RA patients and anti-citrullinated protein antibody (ACPA)-positive individuals at risk developing RA.Single (n = 7,680) were phenotyped isolated BAL 3) diagnosis 9). immunoglobulin variable region transcripts sequenced selected expression monoclonal antibodies...
Summary High mobility group box protein 1 (HMGB1) was previously considered a strict nuclear protein, but lately data are accumulating on its extranuclear functions. In addition to potent proinflammatory capacities, HMGB1 has prominent role in number of processes specific interest for the placenta. Our overall aim investigate expression human term placenta and elucidate potential difference comparing vaginal deliveries with elective Caesarean sections. addition, placentas from normal...
Abstract An increased repertoire of potential osteoclast (OC) precursors could accelerate the development bone-erosive OCs and consequent bone damage in rheumatoid arthritis (RA). Immature dendritic cells (DCs) can develop into OCs, however, mechanisms underlying this differentiation switch are poorly understood. We investigated whether protein citrullination RA-specific anti–citrullinated Abs (ACPAs) regulate human blood–derived DC–OC transdifferentiation. show that plasticity toward OC...
Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by synovial inflammation and joint destruction. Cell-derived small extracellular vesicles (sEV) mediate cell-to-cell communication in the microenvironment carrying microRNAs (miRs), class of non-coding RNAs. Herein, we report that sEV from fluid promote osteoclast differentiation which attributed to high levels miR-574-5p. Moreover, demonstrate for first time enhanced maturation mediated Toll-like receptor (TLR) 7/8...
Abstract Objective Individuals positive for anti-cyclic-peptide-antibodies (anti-CCP) and musculoskeletal complaints (MSK-C) are at risk developing rheumatoid arthritis (RA). In this study we aimed to investigate factors involved in progression. Methods Anti-CCP2-positive individuals with MSK-C referred a rheumatologist were recruited. lacked clinical ultrasound examination followed ≥3 years or until diagnosis. Blood samples from inclusion analysed nine ACPA reactivities (citrullinated...
PGE2 is a potent lipid mediator of pain and oedema found elevated in RA. Microsomal prostaglandin E synthase-1 (mPGES-1) terminal enzyme the pathway inducible by proinflammatory cytokines. mPGES-1 markedly upregulated RA synovial tissue despite antirheumatic treatments, suggesting that multiple inflammatory stimuli contribute to its induction. High-mobility group box chromosomal protein 1 (HMGB1) known induce inflammation both direct interaction with TLR4 enhancement other molecules...
Abstract Gold compounds such as gold sodium thiomalate (GST) can reduce the symptoms of rheumatoid arthritis (RA), although their mechanism action is not well defined. As proinflammatory mediator high mobility group box chromosomal protein 1 (HMGB1) may play a role in pathogenesis RA, we have performed vitro studies to investigate whether GST inhibits HMGB1 release basis its mode action. Murine RAW 264.7 or human THP-1 macrophage cells were stimulated culture with agents causing...
Several HMGBl-specific antagonists have provided beneficial results in multiple models of inflammatory disease-preclinical trials including arthritis. Since no HMGB1-specific targeted therapy has yet reached the clinic, we performed vitro studies to investigate whether any a selection well-established antirheumatic drugs inhibit HMGB1 release as part its mode action. Freshly purified peripheral blood monocytes from healthy donors were stimulated cultures with LPS and IFNγ cause TNF detected...
High mobility group box chromosomal protein 1 (HMGB1) is a nuclear that acts as pro-inflammatory mediator following extracellular release. The aberrantly expressed extracellularly in the settings of clinical and experimental synovitis. Therapy based on HMGB1 antagonists has shown encouraging results arthritis warrants further scientific exploration using independent methods. In present study we asked whether sequestration preventing release would be beneficial for synovitis...
Abstract High mobility group box protein 1 (HMGB1) exerts different biological functions dependent on its cellular localization. Nuclear HMGB1 maintains chromatin architecture and is required for undisturbed transcription activity, extracellularly released mediates inflammation tissue regeneration. A present paucity of readily accessible methods to quantify represents a problem concerning the exploration biology. We have now developed HMGB1-specific ELISPOT assay enabling enumeration...
Patient and public involvement (PPI) improves the quality of health research ensures that is relevant to patients' needs. Though PPI increasingly evident in clinical services research, there are few examples literature effective translational laboratory-based research. In this paper, we describe development evaluation a multi-centre European project (EuroTEAM - Towards Early biomarkers Arthritis Management) included both psychosocial We found although most EuroTEAM was centred around were...
Why the adaptive immune system turns against citrullinated antigens in rheumatoid arthritis (RA) and whether anti-citrullinated protein antibodies (ACPAs) contribute to pathogenesis are questions that have triggered intense research, but still not fully answered. Neutrophils may be crucial this context, both as sources of also targets ACPAs. To better understand how ACPAs neutrophils RA, we studied reactivity a broad spectrum RA patient-derived ACPA clones activated or resting neutrophils,...
The occurrence of autoantibodies is a hallmark rheumatoid arthritis, specifically those targeting proteins containing the arginine-derived amino acid citrulline. There strong evidence showing that anticitrullinated protein/peptide antibodies (ACPA) are involved in disease progression, and ACPA was recently shown to induce pain animals. Here, we explore novel concept useful for research, diagnostics, possibly therapy autoimmune diseases, namely, directly target neutralize using peptide...
Background: In rheumatoid arthritis (RA) the cause for loss of tolerance and anti-citrullinated protein antibody (ACPA) production remains unidentified. Mouse studies showed that lymph node stromal cells (LNSCs) maintain peripheral through presentation tissue antigens (PTAs). We hypothesize dysregulation mechanisms in human LNSCs might underlie pathogenesis RA. Method: Lymph (LN) needle biopsies were obtained from 24 RA patients, 23 individuals positive RA-associated autoantibodies but...
<h3>Background and objectives</h3> Circulating levels of IL-8 is related to the bone loss associated with breast cancer metastasis. Recently, we have shown that anti-citrullinated protein antibodies (ACPA) can induce osteoclastogenesis. We aimed investigate role its receptors in mediating osteoclastogenesis presence or absence ACPAs <h3>Methods</h3> was measured by ELISA serum risk RA patients synovial fluid samples patients. CD14 positive monocytes were used generate osteoclasts M-CSF...
<h3>Background</h3> Circulating levels of IL-8 is related to the bone loss associated with breast cancer metastasis. Recently, we have shown that anti-citrullinated protein antibodies (ACPA) can induce osteoclastogenesis. <h3>Objectives</h3> We aimed investigate role and its receptors in mediating osteoclastogenesis presence or absence ACPAs <h3>Methods</h3> was measured by ELISA serum risk RA patients synovial fluid samples patients. CD14 positive monocytes were used generate osteoclasts...
<h3>Background</h3> Individuals testing positive for anti-cyclic-citrullinated-peptide-antibodies (Anti-CCP) and musculoskeletal (MSK) complaints are at risk developing rheumatoid arthritis (RA). <h3>Objectives</h3> We aim to identify factors involved in progression a population considered RA. <h3>Methods</h3> Anti-CCP-positive individuals with MSK referred rheumatologist the Region Stockholm were recruited. lacked clinical ultrasound examination followed ≥3 years or until diagnosis was...
BackgroundThe endogenous, nuclear protein High Mobility Group Box chromosomal 1(HMGB1) is secreted by activated macrophages/monocytes and, once extracellular, promotes infl ammation.Extracellular HMGB1 present in the synovitis of patients with rheumatoid arthritis (RA) and blockade specifi c antibodies ameliorates experimental arthritis.In addition, intra-articular injections recombinant induce mice.The authors hypothesise that represents an endogenous mediator as well a target molecule for...