During the past 20 years, the development of telemedicine has accelerated due to the rapid advancement and implementation of more sophisticated connected technologies. In rheumatology, e-health interventions in the diagnosis, monitoring and mentoring of rheumatic diseases are applied in different forms: teleconsultation and telecommunications, mobile applications, mobile devices, digital therapy, and artificial intelligence or machine learning. Telemedicine offers several advantages, in particular by facilitating access to healthcare and providing personalized and continuous patient monitoring. However, some limitations remain to be solved, such as data security, legal problems, reimbursement method, accessibility, as well as the application of recommendations in the development of the tools.
ObjectivesMesenchymal stem/stromal cells (MSCs) are widely investigated in regenerative medicine thanks to their immunomodulatory properties. They exert their anti-inflammatory function thanks to the secretion of a number of mediators, including proteins and miRNAs, which can be released in the extracellular environment or in the cargo of extracellular vesicles (EVs). However, the role of miRNAs in the suppressive function of MSCs is controversial. The aim of the study was to identify miRNAs that contribute to the immunomodulatory function of human bone marrow-derived MSCs (BM-MSCs).MethodsHuman BM-MSCs were primed by coculture with activated peripheral blood mononuclear cells (aPBMCs). High throughput miRNA transcriptomic analysis was performed using Human MicroRNA TaqMan® Array Cards. The immunosuppressive function of miRNAs was investigated in mixed lymphocyte reactions and the delayed type hypersensitivity (DTH) murine model.ResultsUpon priming, 21 out of 377 tested miRNAs were significantly modulated in primed MSCs. We validated the up-regulation of miR-29a, miR-146a, miR-155 and the down-regulation of miR-149, miR-221 and miR-361 in additional samples of primed MSCs. We showed that miR-155 significantly reduced the proliferation of aPBMCs in vitro and inflammation in vivo, using the DTH model. Analysis of miRNA-mRNA interactions revealed miR-221 as a potential target gene that is down-regulated by miR-155 both in primed MSCs and in aPBMCs.ConclusionHere, we present evidence that miR-155 participates to the immunosuppressive function of human BM-MSCs and down-regulates the expression of miR-221 as a possible inflammatory mediator.
Background Several reports have found an association between gout and osteoarthritis (OA). Urate levels in OA synovial fluid has been shown to associate with both knee OA severity and production of proinflammatory cytokines. However, the impact of serum urate (SUA) levels on pain and disability or radiographic damages in patients with established knee or hip OA remains unknown Objectives To search for an association between SUA levels and OA severity and OA symptoms in a cross-sectional analysis of a large cohort of patients Methods Data are from 863 subjects with knee or hip OA from the KHOALA (Knee and Hip Osteo-Arthritis Long-Term Assessment) cohort. For each patient, SUA, CRPus, serum adipokines and lipids levels were assessed at inclusion. Baseline clinical data included the WOMAC (total, pain, stiffness and function) and the Harris, the IKS and Osteoarthritis Knee and Hip Quality of Life (OAKHQOL) scores. Associations between SUA levels and OA symptoms and disability was searched using uni and multivariate linear regression and associations between SUA levels and the presence of one or more radiographic OA with multivariate logistic regression. Results 863 patients (69.1% women) were included. Mean age was 61.9 (±8.5) years and mean BMI 29.4 (±6) kg/m2 . 87 (10.1%) patients had diabetes. OA involved uni- or bilateral knees in 653 patients and uni- or bilateral hip in 286 patients. Mean SUA levels was 340 μmol/l (range 110.0-910.0). Hyperuricemia (SUA >360 μmol/l) was observed in 305 (35.3%) patients. The level of uricemia was weakly correlated with BMI (r=0.23), insulinemia (r=0.273) and the triglycerides level (r=0.296). SUA levels did not significantly correlate with the WOMAC, the Harris, the IKS or the OAKHQOL scores in patients with either symptomatic knee or hip OA. In addition, SUA was not associated with the number of symptomatic knee or hip OA joints or radiographic knee or hip OA joints Conclusions In this large cohort of patients with knee or hip OA, SUA levels were not associated with OA symptoms, severity or radiographic damages. Such results do not exclude a prognostic value of SUA on OA progression. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.3864
BackgroundRituximab (RTX) may be responsible for infectious event in RA patients. Immunological markers may be associated with the occurrence of infections.ObjectivesTo evaluate lymphocyte counts and immunoglobulin concentrations over multiple cycles of RTX in RA patients, and to analyse the relationship between these markers and the occurrence of infections.MethodsRetrospective monocentric study on 94 RA patients treated with RTX. At baseline and during follow up, lymphocyte phenotyping (CD4+, CD3+, CD19 +cells), gammaglobulin, IgG, IgM and IgA concentration were assessed. Patients were dichotomized according to the absence or presence of infectious events. A student’s test was used to compare the continuous variables and a Chi2 test or the Fisher test was used for the dichotomous variables.ResultsA total of 119 infectious events occurred during follow-up, of which only 11 were serious, with respective incidences of 65 per 100 patient-years and 6 per 100 patient-years. Low IgM concentration at RTX initiation and low IgG concentration (<5 g/L) throughout follow-up were associated with an increased risk of infection. Both gammaglobulin and IgG concentrations decreased along with successive cycles of RTX in patients with infection, while they remained stable in patients without infection. Twelve patients had a CD4 +cell count<200/mm3 during follow up, of which one with a CD4 +cell count 233/mm3 at baseline, who subsequently presented an opportunistic infection.ConclusionsGammaglobulin, IgM and IgG concentrations and CD4 +cell count are valuable before RTX initiation in RA patients. IgG or gammaglobulin concentration should also be monitored before each cycle. CD4 +lymphocytes monitoring should be considered in patients with low value at initiation.Disclosure of InterestF. Martins: None declared, A. Bensalem: None declared, T. Bejan-Angoulvant: None declared, A. Lhommas: None declared, J. Mélet: None declared, S. Mammou: None declared, G. Thibault: None declared, L. Bernard: None declared, P. Goupille Consultant for: Abbvie, Biogaran, BMS, Hospira, Janssen-Cilag, MSD, Pfizer, Sanofi-Genzyme and UCB, D. Mulleman Grant/research support from: Abbvie and Nordic Pharma, Consultant for: MSD, Novartis, UCB and Pfizer
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