Multi-tiered proteome analysis displays the hyper-permeability of the rheumatoid synovial compartment for plasma proteins.

Rheumatoid arthritis (RA) is characterized by synovial hyperplasia and cartilage/bone destruction. RA affects the synovial joints, the synovial lining and the permeability of the synovium. As the latter is of central relevance for the distribution of systemically delivered therapeutics into synovial fluid (SF), we here assessed the protein composition of paired plasma and SF of patients diagnosed with RA at three distinct levels of depth using mass spectrometric approaches: the "total" proteome, the "total" IgG1 antibody repertoire and the RA-specific ACPA IgG1 autoantibody repertoire.

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.

Autoreactive B cells remain active despite clinical disease control in rheumatoid arthritis.

Background: Autoimmune diseases (AIDs) are frequently hallmarked by the presence of autoreactive B cell responses which are involved in disease pathogenesis. However, the dynamics of such responses and their relation to clinical disease activity in humans is poorly understood. Rheumatoid arthritis (RA), a prototypic chronic AID, is hallmarked by B cell responses directed against citrullinated proteins.

Pathogenic role of anti-nuclear autoantibodies in systemic sclerosis: Insights from other rheumatic diseases.

Systemic sclerosis (SSc) is a severe autoimmune disease characterized by vasculopathy, fibrosis, and dysregulated immunity, with hallmark autoantibodies targeting nuclear antigens such as centromere protein (ACA) and topoisomerase I (ATA). These autoantibodies are highly prevalent and disease-specific, rarely coexisting, thus serving as crucial biomarkers for SSc diagnosis. Despite their diagnostic value, their roles in SSc pathogenesis remain unclear.

Circulating levels of endogenous complement inhibitors correlate inversely with complement consumption in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is marked by excessive complement activation, contributing to tissue damage. Complement activation can be detected in many organs including the skin, kidney, and brain. The involvement of the central nervous system is particularly relevant to understanding neuropsychiatric SLE (NPSLE), one of the poorest understood manifestations of SLE for which no biomarkers are available.

Acetylated bacterial proteins as potent antigens inducing an anti-modified protein antibody response.

Objective: Gut-residing bacteria, such as , can acetylate their proteome under conditions of amine starvation. It is postulated that the (gut) microbiome is involved in the breach of immune tolerance to modified self-proteins leading to the anti-modified protein antibodies (AMPAs), hallmarking seropositive rheumatoid arthritis (RA). Our aim was to determine whether acetylated bacterial proteins can induce AMPA responses cross-reactive to modified self-proteins and be recognised by human AMPA (hAMPA).

Prednisone use, disease activity and the occurrence of hyperglycaemia and diabetes in patients with early rheumatoid arthritis: a 10-year subanalysis of the BeSt study.

Objectives: To assess whether prednisone use and/or disease activity score (DAS) are associated with the development of hyperglycaemia and diabetes in rheumatoid arthritis (RA).

Methods: We included 504 non-diabetic early RA patients from the BeSt study (Dutch acronym for treatment strategies). Patients were randomised to four DAS-steered treatment arms and followed for 10 years.

Antigen-specific Fab profiling achieves molecular-resolution analysis of human autoantibody repertoires in rheumatoid arthritis.

The presence of autoantibodies is a defining feature of many autoimmune diseases. The number of unique autoantibody clones is conceivably limited by immune tolerance mechanisms, but unknown due to limitations of the currently applied technologies. Here, we introduce an autoantigen-specific liquid chromatography-mass spectrometry-based IgG1 Fab profiling approach using the anti-citrullinated protein antibody (ACPA) repertoire in rheumatoid arthritis (RA) as an example.

Can Pharmacological Conditioning as an Add-On Treatment Optimize Standard Pharmacological Treatment in Patients with Recent-Onset Rheumatoid Arthritis? A Proof-of-Principle Randomized Clinical Trial.

Medication regimens using conditioning via variable reinforcement have shown similar or improved therapeutic effects as full pharmacological treatment, but evidence in patient populations is scarce. This proof-of-principle double-blind randomized clinical trial examined whether treatment effects in recent-onset rheumatoid arthritis (RA) can be optimized through pharmacological conditioning. After four months of standardized treatment ( = 46), patients in clinical remission ( = 19) were randomized to the Control group (C), continuing standardized treatment ( = 8), or the Pharmacological Conditioning (PC) group, receiving variable treatment according to conditioning principles ( = 11).

Risk Factors for Antiphospholipid Antibodies and Antiphospholipid Syndrome.

Persistence of serum antiphospholipid antibodies (aPL) is associated with a high thrombotic risk, both arterial and venous, and with pregnancy complications. Due to the potential morbidity and mortality associated with the presence of aPL, identifying and recognizing risk factors for the development of aPL and thrombosis in aPL carriers may help to prevent and reduce the burden of disease. Multiple elements are involved in the pathomechanism of aPL development and aPL-related thrombosis such as genetics, malignancy, and infections.

Anti-carbamylated protein antibodies in systemic sclerosis.

Background: To investigate the presence of different isotypes of anti-carbamylated protein (CarP) antibodies in systemic sclerosis (SSc) patients and its association with skin involvement.

Methods: Sera of 194 SSc patients from the Leiden CCISS cohort, fulfilling ACR/EULAR 2013 criteria and a clinical diagnosis of SSc, 83 patients with other connective tissue diseases/Raynaud's Phenomenon, 24 rheumatoid arthritis patients and 98 age and sex-matched healthy controls were tested for the presence of anti-CarP IgG, IgA and IgM, determined by ELISA. Clinical characteristics, that were evaluated in SSc patients, included age, anti-topoisomerase antibodies (ATA), anti-centromere antibodies (ACA) and modified Rodnan Skin Score (mRSS).

Repair of joint damage in patients with rheumatoid arthritis does not relate to previous suppression of inflammation: a subanalysis after 8 years treat-to-target in the BeSt-trial.

Objectives: To investigate whether repair of erosions and joint space narrowing (JSN) in rheumatoid arthritis (RA) occurs and whether clinical variables predict this.

Methods: Eight-year follow-up data of the BeSt-study were used. Patients with recent onset RA (1987 criteria) were randomised to four treatment strategies and treated-to-target (Disease Activity Score (DAS)≤2.

Step forward in early recognition of systemic sclerosis: data from the Leiden CCISS cohort.

Background: Since 2009, Dutch patients with a confirmed diagnosis/suspicion of systemic sclerosis (SSc) can be referred to the Leiden Combined Care in Systemic Sclerosis (CCISS) cohort. This study evaluated whether early recognition of SSc has improved over time and whether disease characteristics and survival has changed over time.

Methods: 643 SSc patients fulfilling American College of Rheumatology/European Alliance of Associations for Rheumatology 2013 SSc criteria were included and categorised into three groups based on cohort-entry year: (1) 2010-2013 (n=229 (36%)), (2) 2014-2017 (n=207 (32%)) and (3) 2018-2021 (n=207 (32%)).

Patterns of clinical joint inflammation in juvenile idiopathic arthritis.

Objectives: We studied patterns of joint inflammation in juvenile idiopathic arthritis (JIA) to assess whether joint activity recurs locally in the same joints.

Methods: Joints of 91 patients of the BeSt for Kids study, a treat-to-target trial for children with recent-onset oligoarticular, rheumatoid factor-negative polyarticular and psoriatic JIA, were clinically assessed during 2 years (10 study visits). The association between joint inflammation at baseline and later inflammation in the same joint was assessed using a multilevel mixed-effects logistic regression model at joint level.

Geo-epidemiology of autoantibodies in rheumatoid arthritis: comparison between four ethnically diverse populations.

Background: Rheumatoid arthritis (RA) occurs across the globe in different ethnic populations. Most RA patients harbor anti-modified protein antibodies (AMPA); however, it is unclear whether differences exist in autoantibody responses at different geographic locations and between different ethnic groups, which could provide new clues regarding factors underlying autoantibody development. We therefore investigated AMPA prevalence and association with HLA DRB1 alleles and smoking in four ethnically diverse populations on four different continents.

Progression from suspected to definite systemic sclerosis and the role of anti-topoisomerase I antibodies.

Introduction: Early diagnosis of systemic sclerosis (SSc) is important to start therapeutic interventions timely. Important risk factors for progression to SSc are the SSc-specific autoantibodies, of whom anti-centromere antibodies (ACA) and anti-topoisomerase I antibodies (ATA) are the most frequent. ATA is associated with a severe disease course.