Longitudinal immunomonitoring following Tocilizumab in rheumatoid arthritis

Poster presentationInternational audienc

Targeted delivery to inflammatory monocytes for efficient RNAi-mediated immuno-intervention in auto-immune arthritis

Poster presentationInternational audienc

Absence of up-regulation for a proliferation-inducing ligand in Sjögren's sialadenitis lesions

Objective. To determine whether a proliferation-inducing ligand (APRIL) has a role in the survival of plasma cells infiltrating salivary glands from SS patients. Methods. We performed immunological staining for APRIL in minor salivary glands from SS with a pair of antibodies specifically recognizing APRIL-producing cells and secreted APRIL. Results. Despite high leucocyte infiltration, APRIL-producing cells, identified as neutrophils, were rare in SS salivary glands. Keratinocytes from the adjacent oral epithelium also produced APRIL, but we never detected significant levels of secreted APRIL in SS salivary glands. We obtained similar results with B-cell lymphomas associated with SS. In fact, there was no significant difference in APRIL production and the level of secreted APRIL in these pathological samples compared with normal corresponding tissues. Conclusion. The combined observation that APRIL production is not up-regulated in lesions from SS patients, and that secreted APRIL is not retained in these lesions, indicates that plasma cells frequently present in SS lesions may not rely on APRIL for survival, as they do in other rheumatic disease

Tolerance to intraoral biofilms and their effectiveness in improving mouth dryness and modifying oral microbiota in patients with primary Sjögren’s syndrome: “Predelfi study”

IntroductionPrimary Sjögren’s syndrome (pSS) is a systemic autoimmune disease characterized by exocrine gland dysfunction. No therapeutic strategy is sufficient on its own for the management of dry mouth and therapeutic innovations are required.MethodsThis Predelfi study was a single-center, prospective, comparative, randomized, double-blind, cross-over controlled study with the primary objective of assessing the tolerance to and effectiveness of two adhesive biofilms (containing prebiotics and, sodium alginate, respectively) in patients with pSS and hyposialia (#NCT04206826 in ClinicalTrials.gov). Secondary objectives were to obtain initial data regarding the clinical effectiveness of such biofilms in the improvement of signs and symptoms related to dry mouth and potential changes in the oral microbiota. Ten pSS patients with pSS were included (9 females and 1 male) with a mean age of 58.1 ± 14.0 years.Results and discussionTolerance to the prebiotic and sodium alginate biofilms was assessed by the patients (visual analog scale [VAS] score 66.7 and 87.6, respectively) and the practitioner (90 and 100, respectively). The absolute changes in the VAS scores at the start and end of each treatment period highlighted an improvement in mouth dryness for the sodium alginate versus the prebiotic biofilm. The VAS scores for other parameters (mouth burning sensation; taste alteration; chewing; swallowing and speech difficulties) remained globally comparable between the two groups. Unstimulated salivary flow showed no changes regardless of the biofilm used. Regarding the oral microbiota, the sodium alginate biofilm increased the abundance of the Treponema genus, whereas the use of the prebiotic biofilm as the first treatment increased the abundance of the genera Veillonella and Prevotella. Nevertheless, the prebiotic biofilm appeared to stimulate “milder” genera with regard to periodontal infections. Furthermore, pre-treatment with the prebiotic biofilm prevented the emergence of the Treponema genus induced by subsequent treatment with the sodium alginate biofilm, suggesting a potential protective effect

Diagnostic accuracy of blood B-cell subset profiling and autoimmunity markers in Sjögren's syndrome.

International audienceThe aims of this study were to evaluate the diagnostic accuracy of blood B-cell subset profiling and immune-system activation marker assays in primary Sjögren's syndrome (pSS) and to assess whether adding these tools to the current laboratory item would improve the American-European Consensus Group (AECG) criteria. METHODS: In a single-center cohort of patients with suspected pSS, we tested the diagnostic performance of anti-SSA, antinuclear antibody (ANA), rheumatoid factor (RF), gammaglobulins, IgG titers, and B-cell ratio defined as (Bm2 + Bm2')/(eBm5 + Bm5), determined using flow cytometry. The reference standard was a clinical diagnosis of pSS established by a panel of experts. RESULTS: Of 181 patients included in the study, 77 had pSS. By logistic regression analysis, only ANA ≥1:640 (sensitivity, 70.4%; specificity 83.2%) and B-cell ratio ≥5 (sensitivity, 52.1%; specificity, 83.2%) showed independent associations with pSS of similar strength. In anti-SSA-negative patients, presence of either of these two criteria had 71.0% sensitivity but only 67.3% specificity for pSS; whereas combining both criteria had 96.2% specificity but only 12.9% sensitivity. Adding either of these two criteria to the AECG criteria set increased sensitivity from 83.1% to 90.9% but decreased specificity from 97.1% to 85.6%, whereas adding both criteria in combination did not substantially modify the diagnostic performance of the criteria set. The adjunction of RF + ANA ≥1:320, as proposed in the new American College of Rheumatology (ACR) criteria, did not improve the diagnostic value of anti-SSA. CONCLUSIONS: Blood B-cell subset profiling is a simple test that has good diagnostic properties for pSS. However, adding this test, with or without ANA positivity, does not improve current classification criteria

Genetic markers in clinical subtypes of juvenile idiopathic arthritis

Poster presentatationInternational audienc

The effect of a community-based group intervention on chronic disease self-management in a vulnerable population

Introduction:Chronic non-communicable diseases (NCDs) are predominantly related to modifiable health behaviors and account for 74% of global deaths at present. Behavior modification through self-management is a strategy to prevent NCDs. Chronic Disease Self-Management Programs (CDSMPs) have demonstrated improvements in health behaviors, health status, and use of healthcare. Objective:We evaluated the effects of a 6-week CDSMP on self-efficacy, health behaviors, mental health, health-related quality of life (HR-QoL), and health responsibilities among vulnerable populations with chronic disease in Europe. Methods: A prospective cohort study with a 6-month pre-post single-group design was conducted in five European countries. The intervention targeted adults with chronic conditions and low socioeconomic status, as well as their caregivers. The intervention was a 6-week community-based CDSMP in a group setting. Outcomes were measured per self-report questionnaire at baseline and 6-month follow-up: self-efficacy, health behaviors, mental health, HR-QoL, and health responsibilities. Results: Of 1,844 participants, 1,248 (67.7%) completed follow-up and attended ≥4 sessions. For the chronic condition group, the following outcome measures at follow-up significantly improved compared with baseline (all P &lt; 0.002): self-efficacy (SEMCD-6 6.7 vs. 6.4), mental health (PHQ-8 6.3 vs. 7.0), HR-QoL (SF-12 PCS 42.3 vs. 40.2, SF-12 MCS 42.8 vs. 41.4), health utility (EQ-5D-5L 0.88 vs. 0.86), self-rated health (EQ-5D-5L 67.2 vs. 63.9), communication with healthcare providers (2.28 vs. 2.11), understanding information (3.10 vs. 3.02), number of doctor visits (3.61 vs. 4.97), accident and emergency department visits (0.25 vs. 0.48), total nights in a hospital (0.65 vs. 1.13), and perceived medical errors (19.6 vs. 28.7%). No significant changes were detected in dietary habits, physical activity, substance use, and sleep and fatigue. For caregivers without a chronic condition, only doctor visits significantly decreased (1.54 vs. 2.25, P &lt; 0.001). Discussion: This CDSMP was associated with improvement in self-efficacy, depression, HR-QoL, and health responsibilities over 6 months in a diverse European population with a chronic condition. However, additional interventions targeting lifestyle risk factors are needed to improve health outcomes.</p

EFFICHRONIC study protocol: A non-controlled, multicentre European prospective study to measure the efficiency of a chronic disease self-management programme in socioeconomically vulnerable populations

Introduction More than 70% of world mortality is due to chronic conditions. Furthermore, it has been proven that social determinants have an enormous impact on both health-related behaviour and on the received attention from healthcare services. These determinants cause h

Transcriptomic analysis links diverse hypothalamic cell types to fibroblast growth factor 1-induced sustained diabetes remission

n rodent models of type 2 diabetes (T2D), sustained remission of hyperglycemia can be induced by a single intracerebroventricular (icv) injection of fibroblast growth factor 1 (FGF1), and the mediobasal hypothalamus (MBH) was recently implicated as the brain area responsible for this effect. To better understand the cellular response to FGF1 in the MBH, we sequenced >79,000 single-cell transcriptomes from the hypothalamus of diabetic Lepob/ob mice obtained on Days 1 and 5 after icv injection of either FGF1 or vehicle. A wide range of transcriptional responses to FGF1 was observed across diverse hypothalamic cell types, with glial cell types responding much more robustly than neurons at both time points. Tanycytes and ependymal cells were the most FGF1-responsive cell type at Day 1, but astrocytes and oligodendrocyte lineage cells subsequently became more responsive. Based on histochemical and ultrastructural evidence of enhanced cell-cell interactions between astrocytes and Agrp neurons (key components of the melanocortin system), we performed a series of studies showing that intact melanocortin signaling is required for the sustained antidiabetic action of FGF1. These data collectively suggest that hypothalamic glial cells are leading targets for the effects of FGF1 and that sustained diabetes remission is dependent on intact melanocortin signaling