Objective To investigate the prevalence and longitudinal evolution of anti‐carbamylated fibrinogen antibodies (ACa‐Fib) of IgG and IgA isotypes in early rheumatoid arthritis (RA), and determine whether these antibodies provide additional diagnostic and prognostic information beyond anti‐cyclic citrullinated peptide antibodies (anti‐CCP) and rheumatoid factors (RF). Methods ACa‐Fib IgG and IgA were quantified by in‐house ELISA at baseline (M0), 6 months (M6), and 24 months (M24) in 619 patients with available 2010 ACR/EULAR classification criteria, including 575 RA patients, from the French ESPOIR cohort. Clinical, biological, and radiographic data were collected. Multivariable models and appropriate statistical analyses were used to assess associations between ACa‐Fib levels and disease activity, therapeutic response, smoking exposure, CRP concentrations, and structural progression. Results At baseline, ACa‐Fib IgG and IgA were detected in 16.6% and 6.3% of anti‐CCP‐negative RA patients, respectively. Baseline ACa‐Fib levels were not associated with therapeutic response or remission. Over 24 months, ACa‐Fib IgG levels decreased whereas IgA levels remained stable. Higher ACa‐Fib IgA levels were associated with longer smoking duration (p=0.003) and cumulative smoking exposure (p=0.016). Patients in the highest quartile of ACa‐Fib IgG (≥20.29 AU) had an increased risk of rapid radiographic progression (global p=0.004). Despite its markedly lower prevalence, ACa‐Fib IgA (≥3.07 AU) was also associated with structural progression (OR=1.9, 95% CI 1.1–3.4, p=0.031). Conclusion The distinct longitudinal behaviour and prognostic associations of ACa‐Fib IgG and IgA highlight a previously underappreciated component of the anti‐CarP response and support their utility as complementary biomarkers for improved risk stratification in early RA. image

Les auto-anticorps occupent une place centrale dans le diagnostic et le pronostic de la polyarthrite rhumatoïde (PR). En pratique courante, les anticorps anti-protéines citrullinées (ACPA) et les facteurs rhumatoïdes (FR) d’isotype IgM, constituent les principaux biomarqueurs immunologiques. Les ACPA présentent une meilleure spécificité diagnostique que les FR, tandis que leur positivité conjointe rend le diagnostic quasi certain et identifie des formes de PR à évolution plus sévère. Des titres élevés sont également associés à la progression structurale et à certaines manifestations extra-articulaires, notamment pulmonaires. Cependant, une proportion importante de patients demeure étiquetée « polyarthrite immunonégative » avec les tests de routine, qui ne détectent qu’une partie du répertoire auto-immun. L’étude des autres isotypes de ces 2 auto-anticorps, notamment des IgA et des auto-anticorps dirigés contre des protéines modifiées (AMPA) pourrait améliorer la caractérisation des formes immunonégatives et affiner la stratification pronostique.

Abstract Background Spondyloarthritis (SpA) has specific features in women and may be triggered by parturition. The peripartum period is marked by musculoskeletal remodelling and IL-17 secreting cell activation to enable childbirth. We therefore hypothesized that peripartum SpA might predominantly involve the entheses and be less dependent on HLA-B27 and TNFα. Methods We conducted a retrospective, observational, case-control study using the Rouen University Hospital’s clinical data warehouse. Delivery dates and symptom onset were available for 154 women with SpA. Characteristics were compared between cases (with peripartum SpA) and controls. Results We identified 58 cases and 96 controls. HLA-B27 (37.3% vs. 52.3%, p-value: 0.04), anterior chest syndrome (74.1% vs. 54.7%, p-value: 0.012 and psoriasis (37.9% vs. 16.8%, p-value: 0.004 were significantly associated with peripartum SpA. Lower rates of biological inflammatory syndrome at TNFα inhibitor introduction, (22.2% vs. 48.1%, p-value: 0.003), of radiographic sacroiliac damage (4% vs. 18.6%, p-value: 0.012 and of MRI sacroiliitis (30.6% vs. 47.4%, p-value: 0.046 were observed in women with peripartum SpA. Also, a lower retention rate of TNFα inhibitors was observed in women with peripartum SpA, 45.6% at 12 months, versus 71.2% controls (Odd ratio: 2.56 [95% CI: 1.34–4.95]). Multivariate survival analysis found a hazard ratio for TNFα inhibitor discontinuation of 2.43 (95% CI: 1.62–3.65) within the first two years of treatment. Conclusions Our study highlights a distinct phenotype of peripartum SpA, and a lower retention rate of TNFα inhibitors suggesting a worse response to these class of bDMARD. Trial registration As we conducted a retrospective study without health care intervention, no prospective registration was done.

Celiac disease (CD) affects the small intestine, leading to a progressive disappearance of intestinal villi, and can be found in association with several other autoimmune and inflammatory conditions. The main objective of this study was to determine the prevalence and the clinical significance of anti-transglutaminase and anti-endomysium antibodies in patients diagnosed with early rheumatoid arthritis (RA) and spondyloarthritis (SpA). We measured anti-transglutaminase and anti-endomysium antibodies in biobanked serum samples at inclusion in two French prospective multicenter cohorts of patients with suspected early rheumatoid arthritis (ESPOIR, n = 713) and spondyloarthritis (DESIR, n = 709). Results were compared with the clinical, laboratory, and radiographic findings obtained in patients during a 10-year follow-up period. In the DESIR cohort, anti-transglutaminase antibodies were evidenced at low levels (less than three times the upper limit of normal) in 2/709 (0.42

Les progrès observés depuis 30 ans dans le domaine de la spondyloarthrite axiale (axSpA) n’ont pas permis de répondre à toutes les questions se posant actuellement dans cette pathologie. Ce manuscrit présente les conclusions de la réunion de la French spondyloArthitiS Task force (FAST) qui s’est tenue à Besançon les 28 et 29 septembre 2023. Un travail préalable en sous-groupe a eu pour objectif d’évaluer l’état actuel des connaissances et d’identifier les besoins non couverts dans différents domaines de la axSpA sélectionnés par le comité de pilotage. Ces différents éléments ont fait l’objet d’une discussion collégiale durant les deux jours de réunion en présentiel. Les différents points de discussion ont ainsi été individualisés en tant que besoins non satisfaits : des biomarqueurs pour le diagnostic précoce et l’activité de la maladie, un dossier électronique commun dédié à la SpA à l’échelle nationale, une meilleure compréhension de la dysbiose dans la maladie, une check-list pour l’adressage au rhumatologue, l’adaptation des seuils des autoquestionnaires au sexe féminin, la mise en place de programmes de dépistage des comorbidités, les nouveaux outils d’imagerie, les approches cellulaires et multi-omiques en recherche, le regroupement, au niveau national, de différentes cohortes et registres, les études de stratégies thérapeutiques, la définition consensuelle de la maladie difficile à traiter et de sa prise en charge, le stade préclinique de la maladie, la maîtrise de l’IA en tant qu’outil dans les différents aspects de la recherche. Ces éléments peuvent représenter un cadre pour l’agenda de la recherche sur l’axSpA pour les années à venir.

Objective: To describe the joint manifestations associated with clonal haematopoiesis and to compare patients with and without VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome. Methods: Patients screened for UBA1 mutations between December 2019 and January 2023 in 7 Normandie (France) hospitals were recruited retrospectively. Results: Thirty patients with a haematological disorder associated with dysimmune manifestations were included: 17 (57%) without UBA1 mutations (non-VEXAS) and 13 (43%) with UBA1 mutations (VEXAS). Thirteen (77%) non-VEXAS patients had joint involvement (arthralgia/arthritis), compared with 4 (31%) VEXAS patients (p value: 0.016). Unsupervised clustering using hierarchical clustering identified two clusters. Cluster 1 (14 patients) had more joint involvement (93% vs 25%, p value: 0.001), less UBA1 mutation (14% vs 69%, p value: 0.008), pulmonary involvement (7% vs 50%, p value: 0.017), chondritis (0% vs 50%, p value: 0.003) and unprovoked venous thrombosis (7% vs 43%, p value: 0.039) than cluster 2 (16 patients). Cluster 1 had more ASXL1 mutations (21% vs 0%). Conclusion: Joint involvement was more frequent in patients with clonal haematopoiesis and dysimmune manifestations unrelated to VEXAS syndrome.

OBJECTIVES:Abatacept (ABA) is used for its ability to dampen T cell co-stimulation and because it could act on antigen-presenting cells in an indoleamine 2,3-dioxygenase (IDO)-dependent manner. The objective of this study was to identify biomarkers of ABA response in rheumatoid arthritis (RA) patients and to determine the involvement of IDO. METHODS:RA patients' samples were collected before and after ABA treatment. Clinical response was assessed after 6 months, macrophage phenotype was assessed by flow cytometry. IDO transcript expression were quantified in blood cells by RT-qPCR. In vitro assay: GM-CSF or M-CSF monocyte-derived macrophages from healthy donors were polarised with LPS, with or without IFN-g, and co-cultured with T cells in the presence of anti-CD3, with or without ABA. Macrophage phenotype and T cell proliferation were assessed. RESULTS:In RA patients, the frequency of CD16- CD64+ CD86high macrophages pre-treatment was increase in ABA good responders compared to non-responders. ABA seemed to increase IDO production. In vitro, ABA reduced the proliferation of T cells activated by anti-CD3 and macrophages differentiated and polarised with GM-CSF+LPS+IFN-γ. This inhibitory effect of ABA was abolished by blockade of IDO. CONCLUSIONS:ABA response in RA patients is associated with a particular pro-inflammatory macrophage phenotype pre-treatment and IDO is required for ABA effect. These findings reveal predictive markers of ABA response and the involvement of the IDO pathway.

This is a systematic literature review on the impact of pharmacists in rheumatology, conducted using the PubMed®, CINAHL®, Cochrane Library®, and Web of science® databases and using the PRISMA 2020 checklist. This review was conducted from 2000 to June 2024. A quality analysis was performed. The selection of articles, as well as all analyses, including quality analyses, were conducted by a pair of pharmacists with experience in rheumatology, and included 24 articles. This study highlights the growth of clinical pharmacy activities in rheumatology and the positive influence of clinical pharmacists on patient care. The implementation of such initiatives has the potential to improve medication adherence, reduce medication-related risks, and optimize associated healthcare costs. All these pharmaceutical interventions aim to make the patient care journey smoother and safer. Additionally, the diversity of available pharmaceutical services caters to the varied needs of rheumatology. Furthermore, outpatient clinical pharmacy is also explored in this field and garners interest from patients. The vast majority of studies demonstrate significant improvement in patient care with promising performance outcomes when pharmacists are involved. This review highlights the diverse range of interventions by clinical pharmacists in rheumatology, which is very promising. However, to better assess the benefits of clinical pharmacists, this activity needs further development and evaluation through controlled and randomized clinical research programs.