Systemic inflammation and lymphocyte activation precede rheumatoid arthritis.

Some autoimmune diseases, including rheumatoid arthritis (RA), are preceded by a critical subclinical phase of disease activity. Proactive clinical management is hampered by a lack of biological understanding of this subclinical 'at-risk' state and the changes underlying disease development. In a cross-sectional and longitudinal multi-omics study of peripheral immunity in the autoantibody-positive at-risk for RA period, we identified systemic inflammation, proinflammatory-skewed B cells, expanded Tfh17-like cells, epigenetic bias in naive T cells, TNF+IL1B+ monocytes resembling a synovial macrophage population, and CD4 T cell transcriptional features resembling those suppressed by abatacept (CTLA4-Ig) in RA patients.

Decay-Accelerating Factor Differentially Associates With Complement-Mediated Damage in Synovium After Meniscus Tear as Compared to Anterior Cruciate Ligament Injury.

We have reported that anterior cruciate ligament (ACL) injury leads to the differential dysregulation of the complement system in the synovium as compared to meniscus tear (MT) and proposed this as a mechanism for a greater post-injury prevalence of post traumatic osteoarthritis (PTOA). To explore additional roles of complement proteins and regulators, we determined the presence of decay-accelerating factor (DAF), C5b, and membrane attack complexes (MACs, C5b-9) in discarded surgical synovial tissue (DSST) collected during arthroscopic ACL reconstructive surgery, MT-related meniscectomy, osteoarthritis (OA)-related knee replacement surgery and normal controls. Multiplexed immunohistochemistry was used to detect and quantify complement proteins.

Multifaceted immune dysregulation characterizes individuals at-risk for rheumatoid arthritis.

Molecular markers of autoimmunity, such as antibodies to citrullinated protein antigens (ACPA), are detectable prior to inflammatory arthritis (IA) in rheumatoid arthritis (RA) and may define a state that is 'at-risk' for future RA. Here we present a cross-sectional comparative analysis among three groups that include ACPA positive individuals without IA (At-Risk), ACPA negative individuals and individuals with early, ACPA positive clinical RA (Early RA). Differential methylation analysis among the groups identifies non-specific dysregulation in peripheral B, memory and naïve T cells in At-Risk participants, with more specific immunological pathway abnormalities in Early RA.

A Review of Difficult-to-Treat Rheumatoid Arthritis: Definition, Clinical Presentation, and Management.

Purpose Of Review: A subset of patients with rheumatoid arthritis (RA) who fail multiple biologic therapies are deemed to have "difficult-to-treat" (D2T) RA. In 2021, a European Alliance of Associations for Rheumatology (EULAR) task force proposed a clinical definition of D2T RA. Here we review RA phenotypes and clinical assessment of RA, propose a different definition of D2T RA, discuss possible D2T RA risk factors, and summarize existing literature on the management of D2T RA.

Potential causal role of synovial complement system activation in the development of post-traumatic osteoarthritis after anterior cruciate ligament injury or meniscus tear.

Anterior cruciate ligament (ACL) injury and meniscal tear (MT) are major causal factors for developing post-traumatic osteoarthritis (PTOA), but the biological mechanism(s) are uncertain. After these structural damages, the synovium could be affected by complement activation that normally occurs in response to tissue injury. We explored the presence of complement proteins, activation products, and immune cells, in discarded surgical synovial tissue (DSST) collected during arthroscopic ACL reconstructive surgery, MT-related meniscectomy and from patients with OA.

Preferences and Insights for Participation in a Rheumatoid Arthritis Clinical Prevention Trial: A Mixed-Methods Study.

Objective: In rheumatoid arthritis (RA), anti-citrullinated protein antibodies (ACPA) can be elevated prior to inflammatory arthritis (IA). The potential to intervene in people with ACPA positivity underpins the development of prevention trials in RA. The Research Participation Influences Study examined factors influencing the decisions of individuals who are ACPA(+) to participate in a prevention trial using qualitative and quantitative methods.

Antibodies to Citrullinated Protein Antigens, Rheumatoid Factor Isotypes and the Shared Epitope and the Near-Term Development of Clinically-Apparent Rheumatoid Arthritis.

Background/purpose: In rheumatoid arthritis (RA) autoantibodies including antibodies to citrullinated protein antigens (ACPA) and rheumatoid factor (RF) can be predictive of incident clinical RA. However, there is limited understanding of how antibody changes over time impact prediction of the likelihood and timing of future clinical RA.

Materials And Methods: We evaluated relationships between ACPA, the shared epitope (SE), RF isotypes and incident RA in a prospective cohort of 90 ACPA(+) individuals without baseline arthritis identified through health-fair testing (i.

Diminished cytokine-induced Jak/STAT signaling is associated with rheumatoid arthritis and disease activity.

Rheumatoid arthritis (RA) is a systemic and incurable autoimmune disease characterized by chronic inflammation in synovial lining of joints. To identify the signaling pathways involved in RA, its disease activity, and treatment response, we adapted a systems immunology approach to simultaneously quantify 42 signaling nodes in 21 immune cell subsets (e.g.

A double-blind, placebo-controlled, phase II, randomized study of lovastatin therapy in the treatment of mildly active rheumatoid arthritis.

Objectives: 3-hydroxy-3-methylglutaryl coenzyme-A (HMG Co-A) reductase inhibitors (statins) are standard treatment for hyperlipidaemia. In addition to lipid-lowering abilities, statins exhibit multiple anti-inflammatory effects. The objectives of this study were to determine whether treatment of patients with RA with lovastatin decreased CRP or reduced disease activity.

Perceived Stress and Inflammatory Arthritis: A Prospective Investigation in the Studies of the Etiologies of Rheumatoid Arthritis Cohort.

Objective: The aim of this study was to determine the association of perceived stress with incident inflammatory arthritis (IA) defined as having at least 1 joint consistent with rheumatoid arthritis (RA)-like synovitis based on examination.

Methods: We conducted a prospective cohort study in the Studies of the Etiologies of Rheumatoid Arthritis cohort. Participants without IA were recruited if they were a first-degree relative of an RA proband or screened positive for anti-citrullinated protein antibody.

The Effect of Pre-Appointment Consultation Triage on Patient Selection and Revenue Generation in a University Rheumatology Practice.

Objective: To evaluate the effectiveness of pre-appointment consult screening to identify patients with autoimmune and inflammatory rheumatic disease (AIRD) and to evaluate the revenue implications of routine outpatient care of patients with AIRD compared to that of non-AIRD patients.

Methods: Using data in the electronic medical records, we retrospectively analyzed all new outpatients who were referred for rheumatology consults during a 9-month period for a final diagnosis and revenue generation for routine outpatient care over 1 year following the consult review or initial evaluation.

Results: A total of 961 patients were referred to the outpatient rheumatology clinic and underwent pre-appointment triage.

The association between omega-3 fatty acid biomarkers and inflammatory arthritis in an anti-citrullinated protein antibody positive population.

Objectives: Higher circulating omega-3 fatty acids (n-3 FAs) are associated with a lower prevalence of anti-CCP antibodies and RF in subjects without RA. We examined whether, in anti-CCP+ subjects, n-3 FAs also play a role in development of inflammatory arthritis (IA).

Methods: At Colorado-based health fairs from 2008 to 2014, participants without a previous diagnosis of RA who were anti-CCP3+ (n = 47) were recruited into a follow-up study; symptom assessments and joint examinations were conducted every 6 months for the determination of IA.

Increased pretreatment serum IFN-β/α ratio predicts non-response to tumour necrosis factor α inhibition in rheumatoid arthritis.

Objective: Studies suggest that circulating type I interferon (IFN) may predict response to biological agents in rheumatoid arthritis (RA). Prediction of response prior to initiating therapy would represent a major advancement.

Methods: We studied sera from a test set of 32 patients with RA from the Auto-immune Biomarkers Collaborative Network Consortium and a validation set of 92 patients with RA from the Treatment Efficacy and Toxicity in Rheumatoid Arthritis Database and Repository registry.

Rheumatoid arthritis is associated with signaling alterations in naturally occurring autoreactive B-lymphocytes.

Immune tolerance established during the development of B lymphocytes can be subverted in mature cells and lead to autoimmunity. This study focuses on the recently discovered subset of CD19(+)CD27(-)IgD(+)IgM(low/-) B cells that recognize self-antigens and have the capacity to produce autoantibodies, but under normal conditions do not generate autoimmune response due to intrinsic signaling inhibition (a condition known as clonal anergy and characterized by impaired antigen receptor signaling). Phosphorylation of intracellular signaling proteins and Ca(2+) responses in anergic B cells were measured by multicolor flow cytometry.

Brief report: airways abnormalities and rheumatoid arthritis-related autoantibodies in subjects without arthritis: early injury or initiating site of autoimmunity?

Objective: To evaluate the presence of pulmonary abnormalities in rheumatoid arthritis (RA)-related autoantibody-positive subjects without inflammatory arthritis.

Methods: Forty-two subjects who did not have inflammatory arthritis but were positive for anti-cyclic citrullinated peptide antibodies and/or ≥2 rheumatoid factor isotypes (a profile that is 96% specific for RA), 15 autoantibody-negative controls, and 12 patients with established seropositive early RA (<1-year duration) underwent spirometry and high-resolution computed tomography (HRCT) lung imaging.

Results: The median age of autoantibody-positive subjects was 54 years, 52% were female, and 38% were ever-smokers; these characteristics were not significantly different from those of autoantibody-negative control subjects.

Susac syndrome and pregnancy: disease management.

Susac syndrome (SS) consists of a triad of vision loss, hearing loss, and encephalopathy due to autoimmune-mediated vascular endothelial injury. Herein we describe a 25-year-old previously healthy woman who presented at 20 weeks' gestation with symptoms of confusion, difficulty walking, and vision and hearing loss. She had branch-retinal artery occlusions on funduscopic examination, and sensorineural hearing loss.

Identification of undiagnosed inflammatory arthritis in a community health fair screen.

Objective: To identify individuals with undiagnosed inflammatory arthritis (IA) and rheumatoid arthritis (RA) in a community health fair screen, and to establish in a health fair setting the diagnostic accuracy of combinations of the Connective Tissue Disease Screening Questionnaire (CSQ) and autoantibody testing for IA.

Methods: Screening for IA/RA was performed at health fair sites using a combination of the CSQ, joint examination, rheumatoid factor, and anti-cyclic citrullinated peptide (anti-CCP) antibody testing. IA was defined as > or =1 swollen joint suggestive of synovitis on joint examination by a trained clinician.

Clonal CD8+ T cell expansions in peripheral blood from human immunodeficiency virus type 1-infected children.

The T cell receptor (TCR) repertoires of 24 human immunodeficiency virus (HIV) type 1-infected children were determined by flow cytometry in combination with sequencing of the highly variable TCR complementarity-determining region 3, permitting a quantitative and qualitative assessment of TCR repertoire. Expanded subsets of CD8(+) cells expressing a particular TCR beta-chain variable region were more commonly identified in HIV-1-infected children than in healthy control subjects (75% vs. 13.