COVID-19 Vaccine in Immunosuppressed Adults with Autoimmune rheumatic Diseases (COVIAAD): safety, immunogenicity and antibody persistence at 12 months following Moderna Spikevax primary series.

Objective: To assess the safety, immunogenicity and cellular responses following the Moderna Spikevax primary series in rheumatic disease.

Methods: We conducted a 12-month, prospective, non-randomised, open-label, comparative trial of adults with either rheumatoid arthritis (RA, n=131) on stable treatment; systemic lupus erythematosus (SLE, n=23) on mycophenolate mofetil (MMF); other rheumatic diseases on prednisone ≥10 mg/day (n=8) or age-matched/sex-matched controls (healthy control, HC, n=58). Adverse events (AEs), humoral immune responses (immunogenicity: IgG positivity for anti-SARS-CoV-2 spike protein and its receptor binding domain, neutralising antibodies (NAbs)), cellular responses (ELISpot) and COVID-19 infection rates were assessed.

Expression of the myeloid inhibitory receptor CLEC12A correlates with disease activity and cytokines in early rheumatoid arthritis.

The myeloid inhibitory receptor CLEC12A negatively regulates inflammation. Reduced CLEC12A expression enhances inflammation in CLEC12A knock-out mice with collagen antibody-induced arthritis. Moreover, CLEC12A internalisation augments human neutrophil activation.

Impairment of chemical hypoxia-induced sphingosine kinase-1 expression and activation in rheumatoid arthritis synovial fibroblasts: A signature of exhaustion?

Sphingosine kinase 1 (SphK1) and 2 (SphK2) have been shown contribute to synovial inflammation in animal models of arthritis. However, low levels of intracellular sphingosine-1 phosphate (S1P) were reported in fibroblast-like synoviocytes (FLS) from patients in the end stage of rheumatoid arthritis (RA) compared to normal FLS. Moreover, the S1P receptor-mediated chemokine synthesis was altered in RAFLS in response to chemical hypoxia.

Gene-environment interactions in Paget's disease of bone.

Objectives: This study explored the role of outdoor and indoor air pollutants in Paget's disease of bone (PDB).

Methods: We performed a survey in 140 French-Canadian patients with PDB, including 39 carriers of p.Pro392Leu mutation (SQSTM1 gene) and 113 healthy not mutated controls.

Effect of a rare genetic variant of TM7SF4 gene on osteoclasts of patients with Paget's disease of bone.

Background: Dendritic Cell-Specific Transmembrane Protein (DC-STAMP) is involved in osteoclastogenesis with a key role in mononucleated osteoclasts fusion. We reported in patients with Paget's disease of bone (PDB) a rare variant (rs62620995) in the TM7SF4 gene, encoding for DC-STAMP, which changes a highly conserved amino acid, possibly damaging according to in silico predictions. This study aimed at determining the functional effects of this variant on osteoclast phenotype in PDB.

Paget's disease of bone: an osteoimmunological disorder?

Osteoimmunology represents a large area of research resulting from the cross talk between bone and immune systems. Many cytokines and signaling cascades are involved in the field of osteoimmunology, originating from various cell types. The RANK/receptor activator of nuclear factor Kappa-B ligand (RANKL)/osteoprotegerin (OPG) signaling has a pivotal role in osteoimmunology, in addition to proinflammatory cytokines such as tumor necrosis factor-α, interleukin (IL)-1, IL-6, and IL-17.

The inflammasome pyrin contributes to pertussis toxin-induced IL-1β synthesis, neutrophil intravascular crawling and autoimmune encephalomyelitis.

Microbial agents can aggravate inflammatory diseases, such as multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). An example is pertussis toxin (PTX), a bacterial virulence factor commonly used as an adjuvant to promote EAE, but whose mechanism of action is unclear. We have reported that PTX triggers an IL-6-mediated signaling cascade that increases the number of leukocytes that patrol the vasculature by crawling on its luminal surface.

Proteinase-activated receptor-2 gene disruption limits the effect of osteoarthritis on cartilage in mice: a novel target in joint degradation.

Objective: Evidence indicates that proteinase-activated receptor (PAR)-2 participates in the degradative processes of human osteoarthritis (OA). We evaluated the in vivo effect of PAR-2 on articular lesions in a PAR-2-knockout (KO) mouse model of OA.

Methods: OA was surgically induced by destabilization of the medial meniscus of the right knee in C57Bl/6 wild-type (WT) and PAR-2 KO mice.

Modulation of OPG, RANK and RANKL by human chondrocytes and their implication during osteoarthritis.

Objectives: Earlier studies suggest the involvement of osteoprotegerin (OPG), RANK and RANK ligand (RANKL) in OA subchondral bone metabolism; however, few studies have looked at their functional consequences on chondrocytes. We compared the expression/production of OPG, RANK and RANKL on human normal and OA chondrocytes, and evaluated, on OA chondrocytes, their modulation by some catabolic factors. Furthermore, the role of OPG and RANKL on the production of catabolic/anabolic factors was assessed.

Treatment with ephrin B2 positively impacts the abnormal metabolism of human osteoarthritic chondrocytes.

Introduction: Members of the ephrin system, the ephrin receptor erythropoietin-producing hepatocellular B4 (EphB4) and its specific ligand, ephrin B2, appear to be involved in the bone remodelling process. We recently showed that their interaction inhibits the resorptive activity of human osteoarthritic (OA) subchondral bone osteoblasts. Hence, we further investigated the possible implication of these ephrin members on the catabolic/anabolic activities of human OA chondrocytes.

Proteinase-activated receptor (PAR)-2 activation impacts bone resorptive properties of human osteoarthritic subchondral bone osteoblasts.

Introduction: In osteoarthritis (OA), the subchondral bone undergoes a remodelling process involving several factors synthesized by osteoblasts. In this study, we investigated the expression, production, modulation, and role of PAR-2 in human OA subchondral bone osteoblasts.

Materials And Methods: PAR-2 expression and production were determined by real-time PCR and flow cytometry, respectively.

Activation of the receptor EphB4 by its specific ligand ephrin B2 in human osteoarthritic subchondral bone osteoblasts.

Objective: Abnormal subchondral bone metabolism is involved in osteoarthritis (OA). It has been suggested that ephrin B2 and its specific receptor EphB4 participate in bone homeostasis. We previously reported that human OA subchondral bone osteoblasts could be classified into 2 subpopulations: low (L), having proresorption properties, and high (H), having proformation properties.

Activation of proteinase-activated receptor 2 in human osteoarthritic cartilage upregulates catabolic and proinflammatory pathways capable of inducing cartilage degradation: a basic science study.

Proteinase-activated receptors (PARs) belong to a family of G protein-coupled receptors. PARs are activated by a serine-dependent cleavage generating a tethered activating ligand. PAR-2 was shown to be involved in inflammatory pathways.