Circulating secretory component-containing anti-citrullinated protein antibodies prior to symptom onset in rheumatoid arthritis.

Objectives: To investigate the occurrence and dynamics of secretory component-containing antibodies towards citrullinated proteins (SC ACPA) in plasma from pre-symptomatic individuals subsequently developing rheumatoid arthritis (RA).

Methods: We studied 319 individuals who had donated plasma prior to RA onset (median predating time 4.7 years), whereof 181 also donated samples after diagnosis.

Evidence of Site-Specific Mucosal Autoantibody Secretion in Rheumatoid Arthritis.

Objective: Anti-citrullinated protein antibodies (ACPA) have been detected in sputum and saliva, indicating that anti-modified protein antibodies (AMPA) can be produced at mucosal sites in patients with rheumatoid arthritis (RA). However, the body's largest mucosal compartment, the gut, has not yet been examined. We therefore investigated the presence of several AMPA (ACPA, anti-carbamylated protein antibodies [anti-CarP], and anti-acetylated protein antibodies [AAPA]) at different mucosal sites, including the intestinal tract.

Effectiveness of JAK Inhibitors Compared With Biologic Disease-Modifying Antirheumatic Drugs on Pain Reduction in Rheumatoid Arthritis: Results From a Nationwide Swedish Cohort Study.

Objective: To compare the effectiveness of JAK inhibitors (JAKis) and biologic disease-modifying antirheumatic drugs (bDMARDs) on pain in patients with rheumatoid arthritis.

Methods: In this retrospective study, we investigated patients with a diagnosis of rheumatoid arthritis, starting treatment with a JAKi (n = 1,827), a tumor necrosis factor inhibitor (TNFi; n = 6,422), an interleukin-6 inhibitor (n = 887), abatacept (n = 1,102), or rituximab (n = 1,149) in 2017 to 2019, using data from several linked Swedish national registers. Differences in change in pain, assessed with a visual analogue scale (0-100 mm), from baseline to 3 months, as well as proportions of patients remaining on initial treatment with low pain (visual analogue scale pain <20) at 12 months, were compared between treatments.

Screening for autoimmune diseases in apparently healthy antinuclear antibody positive individuals.

Background: Anti-nuclear antibodies (ANA) assessed by immunofluorescence (IF) microscopy are associated with systemic autoimmune rheumatic diseases (SARD) and can be detected years before onset of clinical symptoms. Recent data indicate dysregulation of the immune system with increased levels of proinflammatory cytokines, including type I interferons (IFN), in ANA-positive versus ANA-negative individuals. Herein, the aims were to investigate IF-ANA, ANA fine specificities, and IFN-α protein levels in relation to self-reported symptoms, as well as clinical signs, of SARD in a large group of healthy blood donors (HBD).

Autoantibodies to joint-related peptides as predictive markers in early rheumatoid arthritis.

Objective: For better management of rheumatoid arthritis (RA), new biomarkers are needed to predict the development of different disease courses. This study aims to identify autoantibodies against epitopes on proteins in the joints and to predict disease outcome in patients with new onset RA.

Methods: Sera from new onset RA patients from the Swedish BARFOT and TIRA-2 cohorts (n = 1986) were screened for autoantibodies to selected peptides (JointIDs) in a bead-based multiplex flow immunoassay.

Exhaled Nitric Oxide Reflects the Immune Reactions of the Airways in Early Rheumatoid Arthritis.

Patients with rheumatoid arthritis (RA) have altered levels of exhaled nitric oxide (NO) compared with healthy controls. Here, we investigated whether the clinical features of and immunological factors in RA pathogenesis could be linked to the NO lung dynamics in early disease. A total of 44 patients with early RA and anti-citrullinated peptide antibodies (ACPAs), specified as cyclic citrullinated peptide 2 (CCP2), were included.

Presence and Immunoreactivity of in Rheumatoid Arthritis.

The presence of periodontal pathogens is associated with an increased prevalence of rheumatoid arthritis (RA). The systemic antibody response to epitopes of these bacteria is often used as a proxy to study correlations between bacteria and RA. The primary aim of the present study is to examine the correlation between the presence of (Aa) in the oral cavity and serum antibodies against the leukotoxin (LtxA) produced by this bacterium.

Obesity is a risk factor for poor response to treatment in early rheumatoid arthritis: a NORD-STAR study.

Objective: This report from the NORD-STAR (Nordic Rheumatic Diseases Strategy Trials and Registries) trial aimed to determine if obesity is associated with response to conventional and biological antirheumatic treatment in early rheumatoid arthritis (RA).

Methods: This report included 793 participants with untreated early RA from the randomised, longitudinal NORD-STAR trial, all of whom had their body mass index (BMI) assessed at baseline. Obesity was defined as BMI ≥30 kg/m.

Elevated Serum Levels of Zonulin Family Peptides in Anticitrullinated Protein Antibody-Positive At-Risk Individuals Without Arthritis.

Objective: Recent advances imply that early events triggering rheumatoid arthritis (RA) occur at mucosal surfaces. We aimed to evaluate whether intestinal permeability is altered in patients at increased risk of RA, and/or predicts the development of clinical arthritis, by measuring serum zonulin family peptides (ZFP) levels, which are shown to reflect intestinal barrier integrity.

Methods: Two independent prospective observational cohorts were studied, including subjects with musculoskeletal symptoms and anticitrullinated protein antibodies (ACPA), but without clinical arthritis at baseline.

Prognostic value of serum protein electrophoresis constituents for arthritis development in anti-citrullinated protein antibody-positive patients with musculoskeletal pain.

Objective: Predictors of arthritis development in patients with anti-citrullinated protein antibodies (ACPAs) and musculoskeletal symptoms are needed for risk stratification and to improve clinical outcomes. The aim of this study was to assess the relationship between serum protein electrophoresis (SPE) constituents and the development of clinical arthritis in ACPA-positive patients with musculoskeletal pain.

Method: We prospectively followed 82 ACPA-positive patients with musculoskeletal pain but no baseline arthritis during a median of 72 months (interquartile range 57-81 months).

L-arginine metabolism inhibits arthritis and inflammatory bone loss.

Objectives: To investigate the effect of the L-arginine metabolism on arthritis and inflammation-mediated bone loss.

Methods: L-arginine was applied to three arthritis models (collagen-induced arthritis, serum-induced arthritis and human TNF transgenic mice). Inflammation was assessed clinically and histologically, while bone changes were quantified by μCT and histomorphometry.

Antigen-presenting autoreactive B cells activate regulatory T cells and suppress autoimmune arthritis in mice.

B cells undergo several rounds of selection to eliminate potentially pathogenic autoreactive clones, but in contrast to T cells, evidence of positive selection of autoreactive B cells remains moot. Using unique tetramers, we traced natural autoreactive B cells (C1-B) specific for a defined triple-helical epitope on collagen type-II (COL2), constituting a sizeable fraction of the physiological B cell repertoire in mice, rats, and humans. Adoptive transfer of C1-B suppressed arthritis independently of IL10, separating them from IL10-secreting regulatory B cells.

Antibodies to leukotoxin A from the periodontal pathogen in patients at an increased risk of rheumatoid arthritis.

Objectives: Periodontitis and underlying bacteria have been linked to the development of rheumatoid arthritis (RA). One suggested pathogen is (.), which expresses leukotoxin A (LtxA) that can citrullinate human proteins, providing a possible trigger for the production of anti-citrullinated protein antibodies (ACPA).

Certolizumab pegol, abatacept, tocilizumab or active conventional treatment in early rheumatoid arthritis: 48-week clinical and radiographic results of the investigator-initiated randomised controlled NORD-STAR trial.

Background: The optimal first-line treatment in early rheumatoid arthritis (RA) is debated. We compared clinical and radiographic outcomes of active conventional therapy with each of three biological treatments with different modes of action.

Methods: Investigator-initiated, randomised, blinded-assessor study.

Antibodies against in serum and saliva and their association with rheumatoid arthritis and periodontitis. Data from two rheumatoid arthritis cohorts in Sweden.

Background: Periodontitis and oral pathogenic bacteria can contribute to the development of rheumatoid arthritis (RA). A connection between serum antibodies to () and RA has been established, but data on saliva antibodies to in RA are lacking. We evaluated antibodies to in serum and saliva in two Swedish RA studies as well as their association with RA, periodontitis, antibodies to citrullinated proteins (ACPA), and RA disease activity.

Resilience to substance use disorder following childhood maltreatment: association with peripheral biomarkers of endocannabinoid function and neural indices of emotion regulation.

Childhood maltreatment (CM) is a risk factor for substance use disorders (SUD) in adulthood. Understanding the mechanisms by which people are susceptible or resilient to developing SUD after exposure to CM is important for improving intervention. This case-control study investigated the impact of prospectively assessed CM on biomarkers of endocannabinoid function and emotion regulation in relation to the susceptibility or resilience to developing SUD.

Pathogenic antibody response to glucose-6-phosphate isomerase targets a modified epitope uniquely exposed on joint cartilage.

Objectives: To identify the arthritogenic B cell epitopes of glucose-6-phosphate isomerase (GPI) and their association with rheumatoid arthritis (RA).

Methods: IgG response towards a library of GPI peptides in patients with early RA, pre-symptomatic individuals and population controls, as well as in mice, were tested by bead-based multiplex immunoassays and ELISA. Monoclonal IgG were generated, and the binding specificity and affinity were determined by ELISA, gel size exclusion chromatography, surface plasma resonance and X-ray crystallography.

Autoantibodies to Disease-Related Proteins in Joints as Novel Biomarkers for the Diagnosis of Rheumatoid Arthritis.

Objective: This study was undertaken to develop and characterize a multiplex immunoassay for detection of autoantibodies against peptides derived from proteins known to play a role in development of arthritis and that are also expressed in joints.

Methods: We selected peptides from the human counterpart of proteins expressed in the joints, based on mouse models that showed these to be targeted by pathogenic or regulatory antibodies in vivo. Using bead-based flow immunoassays measuring IgG antibodies, we selected triple helical or cyclic peptides, containing the epitopes, to avoid collinear reactivity.

Serum serotonin levels are elevated in patients with increased risk of rheumatoid arthritis.

Background: Even though serotonin (5-HT) has been ascribed immunomodulatory features, very little is known about its role in chronic inflammatory diseases. Serotonin is implicated in inflammation and increased levels have been associated with progression of bone erosions in RA.

Objective: To investigate serum serotonin levels in patients with increased risk of rheumatoid arthritis (RA) and patients with recent-onset disease.

The association between autoantibodies and risk for venous thromboembolic events among patients with rheumatoid arthritis.

Objectives: To assess the association between venous thromboembolic (VTE) events and autoantibodies, following patients from RA diagnosis, measuring occurrence, levels and collective load of different autoantibodies against post-translational protein modifications, in particular recognizing citrullination (e.g. citrullinated fibrinogen) and RF by isotype.

IgA rheumatoid factor in rheumatoid arthritis.

Objectives: Rheumatoid factor (RF) is a well-established marker for the diagnosis and classification of rheumatoid arthritis (RA). Most studies evaluated IgM RF or isotype-nonspecific total RF assays. We evaluated the added value of IgA RF in this context.

Standardisation of ACPA tests: evaluation of a new candidate reference preparation.

Introduction: Commercial assays measuring antibodies to citrullinated protein/peptide (ACPA) show poor quantitative agreement. The diagnostic industry has never adopted the International Union of Immunological Societies-Centers for Disease Control and Prevention (IUIS-CDC) ACPA reference standard. Recently, the National Institute for Biological Standards and Control (NIBSC) prepared a new candidate ACPA standard (18/204).