Osteoarthritis (OA) is a prevalent and heterogeneous joint disease in which synovial inflammation drives structural progression and pain. Despite the recognized heterogeneity of OA, the cellular and molecular organization of synovial tissue remains poorly characterized and defining distinct histological and immune endotypes could guide precision medicine and therapeutic targeting. We show that histologically defined synovial pathotypes are conserved across independent cohorts and correspond to distinct molecular immune endotypes. Integration of bulk and spatial transcriptomics with proteomics revealed niche-specific gene and protein signatures, reflecting the anatomical and functional diversity of OA synovium. The lympho-myeloid pathotype was characterized by mature ectopic lymphoid structures containing CD21+CD23+ follicular dendritic cells, spatially organized T and B cell zones, and clonally expanded T and B cells with shared immune cell receptor motifs, consistent with local adaptive immune activity correlating with radiological joint damage. These findings highlight how immune organization and cellular composition shape OA pathogenesis and provide a framework for endotype-guided stratification and therapeutic targeting. ### Competing Interest Statement The authors have declared no competing interest. Institut National de la Santé et de la Recherche Médicale, ATIP-Avenir Région Pays de la Loire, PULSAR Fondation pour la Recherche Médicale, https://ror.org/04w6kn183, ARF202004011786 and EQU202303016276 Fondation Arthritis, https://ror.org/01cqrth30, SPOTT National Institute for Health and Care Research, NIHR203330

OBJECTIVES:Ultrasound (US) is a valuable tool to detect inflammation in peripheral psoriatic arthritis (pPsA). This multicentre study assessed the intra- and inter-reader reliability of US-detected elementary lesions in peripheral psoriatic arthritis (pPsA) and evaluated the impact of standardized training on reliability, as a first step to guide multicentre assessment in the APACHE cohort. METHODS:A cross-sectional study was conducted to analyse the reliability of pPsA US lesions, as a first step in an ongoing predictive cohort (APACHE, NCT03768271) study. Three web-based reliability exercises were carried out between 2020 and 2024. Inter-rater and intra-rater reliability were assessed using Light's kappa (κ). During the third reliability exercise, a reference atlas of elementary US lesions in dactylitis was developed. RESULTS:Experienced and trainee sonographers from 30 recruiting centres participated into the study. In step 1, intra-reader kappas were moderate-to-good for synovitis (0.50-0.80), tenosynovitis (0.51-0.63), enthesitis (0.62-0.73), and poor for dactylitis (0.31-0.47); inter-reader kappas were lower for synovitis (0.32-0.70), tenosynovitis (0.40-0.49), enthesitis (0.47-0.60) and dactylitis (0.13-0.24). In Step 2, reliability improved notably in expert and trainees except for dactylitis [intra-reader: synovitis (0.81-0.90), tenosynovitis (0.66-0.83), enthesitis (0.61-0.81), dactylitis (0.37-0.47); inter-reader: synovitis c(0.72-0.84), tenosynovitis (0.55-0.76), enthesitis (0.37-0.59), dactylitis (0.12-0.30)]. Step 3 achieved moderate-to-good reliability for dactylitis (intra 0.69-0.80, inter 0.46-0.68). An atlas was produced based on expert consensus and lesion identification rates among sonographers. CONCLUSION:Standardized training was associated with a marked improvement in intra- and inter-reader reliability for the assessment of elementary pPsA lesions. The consensus-based US atlas provides practical guidance for identifying challenging dactylitis-related lesions in clinical and research settings.

Background: This study aimed to assess whether radiographic progression at 12 months differs among patients with rheumatoid arthritis (RA) treated with three treat-to-target strategies to define synovitis: clinical assessment (C-arm), clinical assessment plus greyscale ultrasound (GSUS) assessment (B-arm), or power Doppler ultrasound (PDUS) assessment alone (D-arm). Methods: We conducted a multicentre, pragmatic, randomized (1:1:1) parallel-group trial between October 10, 2015, and November 25, 2022. RA patients (2010 ACR/EULAR criteria) on stable therapy were randomized into the C-arm (clinical assessment), B-arm (clinical evaluation of 26 joints with GSUS of the shoulders and metatarsophalangeal joints), or D-arm (PDUS assessment of 38 joints) at a 1:1:1 ratio to be evaluated every 3 months for 1 year. The primary endpoint was radiographic progression at 12 months (increase >1 point in the total modified Sharp van der Heijde score). Findings: Among 545 randomized patients, 513 completed the 12-month follow-up (169 C-arm, 171 B-arm, and 173 D-arm). At 12 months, there was no difference in radiographic progression according to the treat-to-target strategy (C-arm 18.9%, B-arm 17.5% and D-arm 18.0%; RR 1.0 [95% CI, 0.7–1.4] for the B-arm versus the C-arm (p= 0.93) and 1.1 [95% CI, 0.8–1.6] for the D-arm versus the C-arm (p=0.49)). The therapeutic strategies did not significantly differ across the three arms. Similarly, at 24 months, the severity of radiographic damage did not differ between the US and C-arm groups. Comparisons of the three strategies revealed no differences in treatment changes, regardless of baseline status (none, biologic only, synthetic only, or combination). Interpretation: While US may identify synovitis and despite its ability to predict radiological evolution, the decision to intensify treatment according to ultrasound rather than clinical evaluation does not modify the long-term progression of RA.

La prescription d’examens complémentaires devant une douleur d’épaule non traumatique repose avant tout sur une évaluation clinique rigoureuse. En l’absence de drapeau rouge, les recommandations HAS 2024 positionnent la radiographie standard comme examen de première intention, réalisée après 4 à 6 semaines d’évolution. Elle permet d’éliminer des diagnostics différentiels osseux et articulaires et doit être adaptée aux hypothèses cliniques (incidences ciblées selon suspicion d’omarthrose, capsulite, tendinopathie, arthropathie acromio-claviculaire ou instabilité). L’échographie constitue également un examen complémentaire de première intention pour les douleurs péri-articulaires, en association avec la radiographie, du fait de son accessibilité, de l’absence d’irradiation et de ses bonnes performances diagnostiques pour la coiffe des rotateurs. Les données de la littérature montrent une excellente sensibilité et spécificité pour les ruptures transfixiantes du supra-épineux, avec une équivalence globale à l’IRM chez des opérateurs expérimentés. La fréquence élevée d’anomalies échographiques chez des sujets asymptomatiques impose une interprétation prudente, en privilégiant la corrélation clinico-radio-échographique afin d’éviter le surdiagnostic et un potentiel effet nocebo. La pertinence de la prescription et l’expertise de l’opérateur sont des déterminants majeurs d’une prise en charge optimale.

The temporomandibular joint (TMJ) is a common cause of orofacial pain. Several imaging techniques can be used to aid diagnosis and management of patients. Ultrasound (US) is a non-ionising, inexpensive and widely available technique. This pictorial review aims to demonstrate the US changes associated with various TMJ disorders. Ultrasound examinations should be standardised and include static and dynamic evaluations of the joint. Several abnormalities can be detected in cases of osteoarthritis, inflammatory arthritis, or disc disorders, such as cortical irregularity, effusion, or disc displacement. Ultrasound also enables joint aspiration, intra-articular injection and synovial biopsy with real-time control. This review also discusses the limitations of this imaging modality, with MRI remaining the gold standard for diagnosis in most cases. Nevertheless, ultrasound can still be considered an extension of clinical examination. It provides rapid and cost-effective diagnostic information and serves as a valuable complement to CBCT and MRI within a multimodal TMJ imaging strategy.

Les pathologies tendineuses sont fréquentes et touchent les adultes de tout âge, incluant les athlètes de haut niveau, les sportifs occasionnels, les travailleurs ou les sujets âgés. Après une lésion tendineuse aiguë, 3 phases successives sont décrites aboutissant à la cicatrisation : une phase inflammatoire suivie d’une phase proliférative puis d’une phase de remodelage. Malgré ce processus, le tendon cicatriciel ne parvient pas à retrouver ses propriétés mécaniques originelles. Dans cette revue, nous proposons de décrire les facteurs-clés impliqués dans le processus de cicatrisation, comme les cellules, les facteurs de transcription, les composants de la matrice extra-cellulaire, les cytokines et facteurs de croissance et la vascularisation. Une meilleure compréhension de ce processus de cicatrisation permettra d’identifier de nouvelles pistes thérapeutiques pour améliorer la récupération des patients, la prise en charge des pathologies tendineuses restant à ce jour un challenge médical.

OBJECTIVES:Despite advances in rheumatoid arthritis (RA) treatment, a significant proportion of patients fail to achieve adequate remission. The dynamic cellular and architectural changes within the synovium that underpin therapeutic success remain poorly understood. This study aimed to unravel the synovial landscape during effective RA treatment, identifying key cellular networks and molecular pathways associated with remission. METHODS:We performed high-dimensional imaging mass cytometry on synovial tissues from healthy controls, patients with osteoarthritis, and patients with early RA longitudinally before and after 6 months of conventional synthetic disease-modifying antirheumatic drugs (csDMARD) therapy. Findings were validated using whole-tissue RNA-sequencing and immunofluorescence in larger patient cohorts, and integrated with ligand-receptor analyses from public single-cell RNA-seq datasets and in vitro functional coculture assays. RESULTS:Our deep spatial profiling pinpointed a critical LYVE1+CD206+tissue-resident macrophage network, localised within perivascular niches alongside fibroblasts and vascular cells. This homeostatic network was disrupted in active RA but restored in patients responding well to csDMARDs. This restoration correlated with the re-establishment of specific cell-cell interactions and was governed by distinct molecular pathways, including chemokines, annexins, and TAM (TYRO3, AXL, MERTK) receptors. Functionally, LYVE1+ macrophages demonstrated a regulatory, anti-inflammatory phenotype in vitro, contrasting with proinflammatory myeloid cells. CONCLUSIONS:This study provides an unprecedented spatial and dynamic blueprint of the RA synovium's response to therapy. We identify the LYVE1+ macrophage network as a pivotal component of synovial homeostasis and its restoration as a hallmark of clinical remission. These findings unveil novel cellular and molecular targets, paving the way for more active therapeutic strategies.

OBJECTIVE:Osteoarthritis (OA) is a debilitating joint disease that is characterized by cartilage degradation, synovial inflammation, and pain. Macrophages have been implicated in OA pathology, but the origins and functions of diverse macrophage subsets seeding the synovial joint tissue remain incompletely understood. This study investigates macrophage heterogeneity, ontogeny, fate, and communication with stromal niche cells in OA. METHODS:Single-cell RNA sequencing was employed on synovial cells isolated from mice with collagenase-induced OA (CiOA) and CD14+ macrophages from four patients with OA. We combined flow cytometry, genetic fate mapping, and imaging mass cytometry to profile synovial macrophage subsets. Cell-cell communication analyses were performed to investigate cellular network interactions. RESULTS:Three macrophage subsets with distinct gene signatures and origins were identified in CiOA, including contributions to synovial inflammation and tissue remodeling. Fate mapping via CCR2-creER and CX3CR1-creER mice revealed the expansion of monocyte-derived TIM4- MHCIIlow/high macrophages. Monocyte-independent TIM4+ CX3CR1+ macrophages operated a synovial niche shift, migrating near vascularized structures in the synovial subintima. Notably, the Oncostatin M (OSM)/OSM receptor (OSMR) signaling network emerged as a critical pathway linking recruited CCR2-derived macrophages to fibroblast activation. In individuals with OA, single-cell transcriptomics identified a conserved MERTKlow CD48high CCR2+ macrophage subpopulation as a key source of OSM. CONCLUSION:Our study provides insights into macrophage subsets and their interplay with the joint microenvironment, bridging the gap between their origins, transcriptomic profiles, and roles in OA. Specifically, the OSM/OSMR axis represents a pivotal mechanism in recruited macrophage-fibroblast crosstalk, offering potential targets for novel biomarkers and therapies to manage OA-related synovitis.

La membrane synoviale est essentielle dans l’homéostasie articulaire et son inflammation caractérise nombre de maladies rhumatismales. Jusqu’à présent, les approches de transcriptomique à haut débit conventionnelles ont amélioré notre compréhension des voies moléculaires associées à l’inflammation synoviale, mais ne permettent pas d’analyser la distribution spatiale des cellules. La biologie spatiale, permettant une cartographie précise des molécules dans leur contexte tissulaire, offre une nouvelle dimension d’information. En rhumatologie, ces techniques ont identifié des sous-types cellulaires et leurs interactions, promettant une médecine plus personnalisée. Cependant, des défis subsistent, notamment en termes de coûts et de gestion des données, notamment pour leur implémentation en clinique. Cette revue a pour but de fournir un tour d’horizon des développements actuels en biologie spatiale dans le domaine de la rhumatologie.

OBJECTIVES:The clinical management of rhizarthrosis relies on several pharmacological approaches, demonstrating variable efficacy. The present study aimed at assessing the potential benefit of the combined infiltration of corticosteroids and hyaluronic acid to reduce trapeziometacarpal osteoarthrisis pain at three months, as compared to the administration of corticosteroids alone. METHODS:We conducted a single-blind trial with two parallel groups and blinded evaluation. Eligible patients (n=150) were randomly assigned to receive hyaluronic acid and corticosteroid (n=74) or saline and corticosteroid infiltrations (n=76. Pain was evaluated one, three, six or twelve months (M1, M3, M6, M12) after infiltration. RESULTS:In total, 149 patients received the injection (mean age 62years old; 83% females). When looking at the primary end point (M3), reduction of pain during activity was greater in the hyaluronic acid+corticosteroid group, as compared to the corticosteroids+placebo (difference -1.1 on a 0-10 points visual analogue scale, 95% confidence interval [-1.9; -0.2], P=0.012). For the secondary end points (visual analogue scores at rest and during activity at M1, M6 and M12), improvements were observed, although not statistically significant (except at M1). Finally, grip and opposition strength remained unchanged between groups along the follow-up. CONCLUSIONS:In patients with painful rhizarthrosis, the infiltrations of hyaluronic acid and corticosteroids demonstrate better efficacy in reducing pain during activity 3months after intervention, compared to injections with only corticosteroids. The present study brings new arguments in favour of the combination of these two drugs for the clinical management of trapeziometacarpal osteoarthrisis.