A5075957668- Rheumatoid Arthritis Research and Therapies
- Monoclonal and Polyclonal Antibodies Research
- Systemic Lupus Erythematosus Research
- T-cell and B-cell Immunology
- Cell Adhesion Molecules Research
- Immunodeficiency and Autoimmune Disorders
- Viral Infections and Immunology Research
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Lymphoma Diagnosis and Treatment
- Cytokine Signaling Pathways and Interactions
- Autoimmune and Inflammatory Disorders Research
- Chronic Lymphocytic Leukemia Research
- Immunotherapy and Immune Responses
- CAR-T cell therapy research
- HER2/EGFR in Cancer Research
- Bone Metabolism and Diseases
- Bone health and treatments
- Toxin Mechanisms and Immunotoxins
- Systemic Sclerosis and Related Diseases
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Glycosylation and Glycoproteins Research
- Immune Cell Function and Interaction
- RNA modifications and cancer
- Lymphadenopathy Diagnosis and Analysis
- Protein Tyrosine Phosphatases
Karolinska University Hospital
2015-2025
Karolinska Institutet
2016-2025
Stockholm Health Care Services
2019-2025
Center for Rheumatology
2024
Thermo Fisher Scientific (Sweden)
2023
Metropolitan University
2023
Amsterdam University Medical Centers
2023
University of Amsterdam
2023
Swedish Rheumatism Association
2021
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...
It has been suggested that immunologic events in the lungs may be involved triggering immunity, particular production of anti-citrullinated protein antibodies (ACPAs) during early phases rheumatoid arthritis (RA). The aim this study was to investigate structural and features incident cases RA relation ACPA presence smoking status.High-resolution computed tomography (HRCT) used examine 105 patients with early, untreated (70 ACPA-positive 35 ACPA-negative RA) 43 healthy individuals....
Abstract Rheumatoid arthritis (RA) is an autoimmune disease affecting synovial joints where different CD4 + T cell subsets may contribute to pathology. Here, we perform single sequencing on cells from anti-citrullinated protein antibodies (ACPA)+ and ACPA- RA patients identify two peripheral helper (T PH ) states a cytotoxic subset. We show that the adhesion G-protein coupled receptor 56 (GPR56) delineates CXCL13 high expressing LAG-3 tissue-resident memory receptors CXCR6 CD69. In SF,...
<h3>Objective</h3> To investigate the role of genetic and environmental factors in development anticitrullinated protein antibodies (ACPA) ACPA-positive rheumatoid arthritis (RA) a twin cohort. <h3>Methods</h3> A total 12 590 twins were analysed for presence ACPAs (CCP2 ELISA), HLA-DRB1 shared epitope (SE) gene alleles, exposure to smoking. Twins with established RA identified national public care registers. Antibody reactivities against citrullinated native forms α-enolase, vimentin,...
Objective The first 3 months after symptom onset represent an important therapeutic window for rheumatoid arthritis (RA). This study investigates the extent and causes of delay in assessment patients with RA eight European countries. Method Data on following levels were collected from 10 centres (Berlin, Birmingham, Heraklion, Lund, Prague, Stockholm, Umeå, Vienna, Warsaw Zurich): (1) symptoms to request see healthcare professional (HCP); (2) HCP by that HCP; (3) initial referral...
Immunological events in the lungs might trigger production of anti-citrullinated protein antibodies during early rheumatoid arthritis (RA). We investigated presence shared immunological citrullinated targets joints and patients with RA.Proteins extracted from bronchial (n=6) synovial (n=7) biopsy specimens RA were by mass spectrometry-based proteomics. One candidate peptide was synthesised used to investigate ELISA (n=393), healthy controls (n=152) disease (n=236). HLA-DRB1 epitope (SE)...
Abstract The inflamed rheumatic joint is a highly heterogeneous and complex tissue with dynamic recruitment expansion of multiple cell types that interact in multifaceted ways within localized area. Rheumatoid arthritis synovium has primarily been studied either by immunostaining or molecular profiling after homogenization. Here, we use Spatial Transcriptomics, where tissue-resident RNA spatially labeled situ barcodes transcriptome-wide fashion, to study local interactions at the site...
Abstract Anti‐cyclic citrullinated peptide2 (CCP2) antibody positivity in rheumatoid arthritis (RA) and the predisease phase, together with success of B‐cell depletion, support a crucial role for B cells RA pathogenesis. Yet, knowledge transition from autoimmunity to is limited, therefore we here investigated changes during risk‐RA phase. phenotypes 18 CCP2‐positive individuals musculoskeletal complaints were studied, parallel ten patients nine healthy controls. Nine progressed RA. using...
Objective Anti-citrullinated protein antibodies (ACPA) are highly specific for rheumatoid arthritis (RA), but the diagnostic accuracy of ACPA in general population has not been thoroughly assessed. We aimed to assess RA and further characterise citrullinated peptide recognition pattern. Methods Serum samples from a large population-representative twin cohort consisting 12 590 individuals were analysed presence using anti-CCP2 ELISA. All ACPA-positive tested on ELISAs four peptide-specific...
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...
OBJECTIVE: In rheumatoid arthritis (RA) several recent efforts have sought to discover means of predicting which patients would benefit from treatment. However, results been discrepant with few successful replications. Our objective was build a biobank DNA, RNA and protein measurements test the claim that current state-of-the-art precision medicine will RA patients. METHODS: We collected 451 blood samples 61 healthy individuals 185 initiating treatment, before treatment initiation at 3 month...
Seropositive rheumatoid arthritis (RA) is characterized by the presence of factor (RF) and anti-citrullinated protein autoantibodies (ACPA) with different fine-specificities. Yet, other serum anti-modified (AMPA), e.g. anti-carbamylated (Carb), -acetylated (KAc), malondialdehyde acetaldehyde (MAA) modified antibodies, have been described. In this comprehensive study, we analyze 30 IgG IgA AMPA reactivities to Cit, Carb, KAc, MAA antigens detected ELISA autoantigen arrays in N=1985 newly...
Based on the epidemiological link between periodontitis and rheumatoid arthritis (RA), unique feature of periodontal bacterium Porphyromonas gingivalis to citrullinate proteins, it has been suggested that production anti-citrullinated protein antibodies (ACPA), which are present in a majority RA patients, may be triggered gum mucosa. To address this hypothesis, we investigated antibody response citrullinated P. peptide relation autoimmune ACPA early RA, examined citrulline-reactivity...
The appearance of anti-citrullinated protein antibodies (ACPAs) in the circulation represents a major risk factor for developing rheumatoid arthritis (RA). Patient-derived ACPAs have been shown to induce pain and bone erosion mice, suggesting an active role pathogenicity RA. We undertook this study investigate whether can tenosynovitis, early sign RA, addition loss these symptoms are dependent on peptidyl arginine deiminase 4 (PAD4).Monoclonal generated from plasma cells RA patients were...
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...
Objective The antibody response against Porphyromonas gingivalis ( Pg ) is elevated in rheumatoid arthritis (RA), especially patients with anti-citrullinated protein antibodies (ACPA). Here, we investigated whether the virulence factor arginine gingipain (Rgp) are associated RA-risk phase and development of arthritis. Methods At-risk individuals were included a prospective study (Risk-RA) based on positive anti-cyclic citrullinated peptide 2 (CCP2) test, having musculoskeletal complaints but...
Introduction: Receptor activator of nuclear factor kappa B ligand (RANKL) is a key regulator bone metabolism.Anti-citrullinated protein antibodies (ACPA) have been suggested to cause destruction by osteoclast activation.We investigated the relationship between RANKL and ACPA in patients with early untreated rheumatoid arthritis (RA).Methods: Patients newly diagnosed RA (n = 183) were analyzed at baseline 3 months after initiating methotrexate (MTX) treatment.Serum (total RANKL), (anti-CCP2)...
HLA class II tetramers can be used for ex vivo enumeration and phenotypic characterisation of antigen-specific CD4+ T cells. They are increasingly applied in settings like allergy, vaccination autoimmune diseases. Rheumatoid arthritis (RA) is a chronic disorder which many autoantigens have been described.Using multi-parameter flow cytometry, we developed multi-HLA tetramer approach to simultaneously study several antigen specificities RA patient samples. We focused on previously described...
The Fc-glycan profile of IgG1 anti-citrullinated peptide antibodies (ACPA) in rheumatoid arthritis (RA) patients has recently been reported to be different from non-ACPA IgG1, a phenomenon which likely plays role RA pathogenesis. Herein we investigate the Fc-glycosylation pattern all ACPA-IgG isotypes and simultaneously detail IgG protein-chain sequence repertoire. serum or plasma (S/P, n = 14) synovial fluid (SF, 4) 18 ACPA-positive RA-patients was enriched using Protein G columns followed...
Methotrexate (MTX) is the standard first-line therapy in rheumatoid arthritis (RA) with variable clinical efficacy that difficult to predict. The glycosylation status of immunoglobulin G (IgG) altered RA and influenced by MTX treatment. We aimed further investigate if IgG untreated early can predict therapeutic response MTX.We used a shotgun proteomic approach screen for Fc glycopeptides serum 12 control subjects 59 patients prior following initiation. treatment was defined according...
Non-coding SNPs in the protein tyrosine phosphatase non-receptor type 2 (PTPN2) locus have been linked with several autoimmune diseases, including rheumatoid arthritis, I diabetes, and inflammatory bowel disease. However, functional consequences of these are poorly characterized. Herein, we show blood cells that PTPN2 highly correlated DNA methylation levels at four CpG sites downstream expression long non-coding RNA (lncRNA) LINC01882 sites. We observed is mainly expressed T anti-CD3/CD28...