Canadian Patients With Axial Spondyloarthritis Require Almost a Decade To Be Diagnosed Leading to Severe Functional Limitation. Results From the International Map of Axial Spondyloarthritis (IMAS).

Objective: To evaluate the sociodemographic characteristics and disease-related factors associated with diagnostic delay in Canadian patients with axial spondyloarthritis (axSpA).

Methods: Data from 542 Canadian patients who participated in the International Map of Axial Spondyloarthritis online survey were analysed. Diagnostic delay was calculated as the difference between age at diagnosis and age at onset of the first symptoms reported by participants.

Changes at Presentation in Patients With Early Rheumatoid Arthritis: A 24-Year Study of the Early Undifferentiated Polyarthritis (EUPA) Cohort.

Objective: To analyze changes in baseline characteristics of patients with very early rheumatoid arthritis (RA) over 24 years in the Early Undifferentiated Polyarthritis (EUPA) cohort.

Methods: Consecutive patients with recent-onset polyarthritis fulfilling RA classification criteria recruited in EUPA were assessed at baseline. Three successive periods were defined: (1) prior to the general availability of biologics (1998-2004; 245 patients), (2) prior to the implantation of the 2010 classification criteria (2005-2010; 266 patients), and (3) the most recent decade (2011-2022; 329 patients).

Osteoclasts and their circulating precursors in rheumatoid arthritis: Relationships with disease activity and bone erosions.

Patients with rheumatoid arthritis (RA) have very different outcomes, particularly with regard to bone erosions. Since osteoclasts are responsible for bone destruction adjacent to rheumatoid synovium, profiling osteoclasts from circulating precursors in RA could help identify patients at risk for bone destruction. In this study, we sought to determine whether the functional characteristics of osteoclasts generated from their blood precursors were modified by RA activity or were intrinsic to osteoclasts and associated with the RA phenotype (erosive or not).

Impending radiographic erosive progression over the following year in a cohort of consecutive patients with inflammatory polyarthritis: prediction by serum biomarkers.

Background/purpose: To evaluate biomarkers as predictors of impending erosion progression.

Methods: Variables were measured at baseline and annually up to 5 years in patients with recent-onset polyarthritis treated to zero swollen joints. Erosive status was defined as ≥5 Units in Sharp/van der Heijde Erosion Score; Rapid Erosive Progression (REP) was defined as an increase ≥5 Units in Erosion Scores between consecutive visits.

Assessing bone impairment in ankylosing spondylitis (AS) using the trabecular bone score (TBS) and high-resolution peripheral quantitative computed tomography (HR-pQCT).

Objectives: To compare bone quality using the trabecular bone score (TBS) and bone microarchitecture in the distal tibia using high-resolution peripheral quantitative computed tomography (HR-pQCT) in ankylosing spondylitis (AS) patients and healthy controls (HC).

Methods: Areal bone mineral density (aBMD) and TBS (TBS iNsight software) were evaluated using DXA (Hologic, QDR 4500); while volumetric bone mineral density (vBMD) and bone microarchitecture were analyzed in the distal tibia using HR-pQCT (Scanco) in 73 male patients with AS and 52 age-matched HC.

Results: AS patients were a mean 41.

Monocytes from male patients with ankylosing spondylitis display decreased osteoclastogenesis and decreased RANKL/OPG ratio.

Unlabelled: The present study investigates the osteoclastogenic capacity of peripheral blood mononuclear cells (PBMCs) in male patients with ankylosing spondylitis (AS). We demonstrated that monocytes from these patients display a lower capacity to generate osteoclasts compared to cells from healthy controls, and osteoclastogenesis was negatively correlated with disease duration.

Introduction: Ankylosing spondylitis (AS) is a disease characterized by new bone growth that leads to syndesmophyte formation but AS patients frequently present with low bone mineral density/fractures.

Chondroitin sulfate efficacy versus celecoxib on knee osteoarthritis structural changes using magnetic resonance imaging: a 2-year multicentre exploratory study.

Background: In osteoarthritis (OA) treatment, although chondroitin sulfate (CS) was found in a number of studies using radiography to have a structure-modifying effect, to date CS use is still under debate. A clinical study using quantitative magnetic resonance imaging (qMRI) is therefore of the utmost importance. Here we report data from a 24-month, randomised, double-blind, double-dummy, controlled, comparative exploratory study of knee OA.

Serum levels of 14-3-3η protein supplement C-reactive protein and rheumatoid arthritis-associated antibodies to predict clinical and radiographic outcomes in a prospective cohort of patients with recent-onset inflammatory polyarthritis.

Background: Age, C-Reactive Protein (CRP) and autoantibodies (Abs) are associated with worse prognosis in patients with recent-onset inflammatory polyarthritis (EPA). Serum 14-3-3η protein is a joint-derived biomarker that up-regulates cytokines and enzymes that perpetuate local and systemic inflammation and may contribute to joint damage. Our objective was to evaluate, over a 5-year prospective period of observation, the additional prognostic potential of serum 14-3-3η protein in EPA patients.

Anti-carbamylated Protein Antibody Levels Correlate with Anti-Sa (Citrullinated Vimentin) Antibody Levels in Rheumatoid Arthritis.

Objective: The presence of anticitrullinated protein antibodies (ACPA) in rheumatoid arthritis (RA) indicates a breach in immune tolerance. Recent studies indicate that this breach extends to homocitrullination of lysines with the formation of anti-carbamylated protein (anti-CarP) antibodies. We analyzed the clinical and serologic relationships of anti-CarP in 2 RA cohorts.

Depressive symptoms predict future simple disease activity index scores and simple disease activity index remission in a prospective cohort of patients with early inflammatory polyarthritis.

Objective: To determine whether depressive symptoms assessed in treated patients with early inflammatory polyarthritis (EPA) influence disease activity during follow-up.

Methods: Consecutively recruited EPA patients were actively treated to remission. Simple disease activity index (SDAI) and Center for Epidemiologic Studies Depression Scale (CES-D) scores were calculated at inclusion and up to 42 months into disease.

Serum C-X-C motif chemokine 13 is elevated in early and established rheumatoid arthritis and correlates with rheumatoid factor levels.

Introduction: We hypothesized that serum levels of C-X-C motif chemokine 13 (CXCL13), a B-cell chemokine, would delineate a subset of rheumatoid arthritis (RA) patients characterized by increased humoral immunity.

Methods: Serum from patients with established RA (the Dartmouth RA Cohort) was analyzed for CXCL13, rheumatoid factor (RF) levels, anticitrullinated peptide/protein antibody (ACPA) and total immunoglobulin G (IgG); other parameters were obtained by chart review. A confirmatory analysis was performed using samples from the Sherbrooke Early Undifferentiated PolyArthritis (EUPA) Cohort.

Cytosolic phospholipase A2 and eicosanoids modulate life, death and function of human osteoclasts in vitro.

Introduction: Eicosanoids are important in bone physiology but the specific function of phopholipase enzymes has not been determined in osteoclasts. The objective of this is study was to determine the presence of cPLA2 in human in vitro-differentiated osteoclasts as well as osteoclasts in situ from bone biopsies.

Materials And Methods: Osteoclastogenesis, apoptosis, bone resorption and the modulation of actin cytoskeleton assays were performed on osteoclasts differentiated in vitro.

Secreted phospholipase A2 type II is present in Paget's disease of bone and modulates osteoclastogenesis, apoptosis and bone resorption of human osteoclasts independently of its catalytic activity in vitro.

Objectives: To study the role of secreted phospholipase A2 (sPLA2) in the pathophysiology of human osteoclasts (OCs).

Methods: Immunohistochemistry and sPLA2 inhibitors were to determine the localization of sPLA2 and its role in OCs biology.

Results: sPLA2 is expressed by OCs from healthy fetal bone and OCs from Paget's disease but not in normal bone.

Prostaglandin D(2) induces apoptosis of human osteoclasts through ERK1/2 and Akt signaling pathways.

In a recent study we have shown that prostaglandin D2 (PGD2) induces human osteoclast (OC) apoptosis through the activation of the chemoattractant receptor homologous molecule expressed on T-helper type 2 cell (CRTH2) receptor and the intrinsic apoptotic pathway. However, the molecular mechanisms underlying this response remain elusive. The objective of this study is to investigate the intracellular signaling pathways mediating PGD2-induced OC apoptosis.

Predictors of pain for patients with early inflammatory polyarthritis.

Objective: To identify predictors of pain at 1 year in patients with early inflammatory polyarthritis (EIP).

Methods: Using a prospective design, patients were examined by a rheumatologist and completed questionnaires at baseline and at 1 year after symptom onset. Separate regression analyses were run for pain intensity, sensory pain, and affective pain.

Monocytes from patients with osteoarthritis display increased osteoclastogenesis and bone resorption: the In Vitro Osteoclast Differentiation in Arthritis study.

Objective: To compare the osteoclastogenic capacity of peripheral blood mononuclear cells (PBMCs) from patients with osteoarthritis (OA) to that of PBMCs from self-reported normal individuals.

Methods: PBMCs from 140 patients with OA and 45 healthy donors were assayed for CD14+ expression and induced to differentiate into osteoclasts over 3 weeks in vitro. We assessed the number of osteoclasts, their resorptive activity, osteoclast apoptosis, and expression of the following cytokine receptors: RANK, interleukin-1 receptor type I (IL-1RI), and IL-1RII.

Prostaglandin D2 induces apoptosis of human osteoclasts by activating the CRTH2 receptor and the intrinsic apoptosis pathway.

Prostaglandin D(2) (PGD(2)) is a lipid mediator synthesized from arachidonic acid that directly activates two specific receptors, the D-type prostanoid (DP) receptor and chemoattractant receptor homologous molecule expressed on T-helper type 2 cells (CRTH2). PGD(2) can affect bone metabolism by influencing both osteoblast and osteoclast (OC) functions, both cells involved in bone remodeling and in in vivo fracture repair as well. The objective of the present study was to determine the effects of PGD(2), acting through its two specific receptors, on human OC apoptosis.

Utility and feasibility of musculoskeletal ultrasonography (MSK US) in rheumatology practice in Canada: needs assessment.

The utility of musculoskeletal ultrasound (MSK US) is being extensively explored and evaluated amongst European rheumatologists. However, utilization of MSK US by rheumatologists in Canada is much less common. This study aimed to evaluate the current use of MSK US in Canadian rheumatology practice, to determine beliefs and attitudes towards MSK US, and to determine factors that may encourage or limit its use.

An interaction between L-prostaglandin D synthase and arrestin increases PGD2 production.

L-type prostaglandin synthase (L-PGDS) produces PGD(2), a lipid mediator involved in neuromodulation and inflammation. Here, we show that L-PGDS and arrestin-3 (Arr3) interact directly and can be co-immunoprecipitated endogenously from MG-63 osteoblasts. Perinuclear L-PGDS/Arr3 co-localization is observed in PGD(2)-producing MG-63 cells and is induced by the addition of the L-PGDS substrate or co-expression of COX-2 in HEK293 cells.

The increased in vitro osteoclastogenesis in patients with rheumatoid arthritis is due to increased percentage of precursors and decreased apoptosis - the In Vitro Osteoclast Differentiation in Arthritis (IODA) study.

Increases in local and systemic bone resorption are hallmarks of rheumatoid arthritis (RA). Osteoclasts are implicated in these processes and their enhanced differentiation may contribute to bone destruction. We observed that in vitro osteoclastogenesis varies among healthy individuals and hypothesized that increased osteoclastogenesis could be a marker for the presence of RA.

Outcomes in recent-onset inflammatory polyarthritis differ according to initial titers, persistence over time, and specificity of the autoantibodies.

Objective: To prospectively evaluate the predictive value of initial titers and subsequent variations of 3 rheumatoid arthritis–associated antibodies for outcomes at 30 months in patients with recent-onset polyarthritis.

Methods: IgM rheumatoid factor (RF), anti-Sa (citrullinated vimentin) antibodies, anti– cyclic citrullinated peptide 2 (anti–CCP-2) antibodies, modified Health Assessment Questionnaire score, Disease Activity Score in 28 joints, and Sharp/van der Heijde radiologic scores were determined at baseline and at 18 and 30 months in a cohort of consecutive HLA–DR-typed treated patients with recent-onset polyarthritis aiming at remission.

Results: At inclusion, 113 (44.

Increased concentrations of prostaglandin D2 during post-fracture bone remodeling.

Objective: To test the hypothesis that increased concentrations of prostaglandin D(2) (PGD(2)) correlate with bone remodeling. Studies using isolated bone cells indicate that PGD(2) may be implicated in the regulation of bone homeostasis, with a positive influence on bone anabolism. We studied patients with traumatic fractures and age- and sex-matched healthy controls as an in vivo model of increased bone remodeling.

Characterization of C-terminal tail determinants involved in CRTH2 receptor trafficking: identification of a recycling motif.

The molecular mechanisms regulating the trafficking of the CRTH2 receptor are poorly understood. In the present study, we characterize C-terminal tail determinants involved in the agonist-induced trafficking of the CRTH2 receptor for prostaglandin D(2). Our results showed that progressive deletion of C-terminal tail residues from amino acid 395 up to 337 gradually impaired CRTH2 internalization by approximately 50% as measured by ELISA in HEK293 cells.

CD40-activated B cells from patients with systemic lupus erythematosus can be modulated by therapeutic immunoglobulins in vitro.

Introduction: Aberrant signaling within and between B and T cells, considered to be central in systemic lupus erythematosus (SLE), could depend on enhanced CD40-CD154 activation. As a result, autoreactive B cells, normally anergic, differentiate and secrete antibodies attacking several normal tissues. Thus restorating B cell homeostasis might help control this disease.