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IRAK3 is upregulated in rheumatoid arthritis synovium and delays the onset of experimental arthritis

<jats:p>Tumour necrosis factor (TNF) is a potent inducer of endotoxin tolerance-associated molecules, such as interleukin-1 receptor-associated kinase 3 (IRAK3), and also a therapeutic target in inflammatory autoimmune diseases, as it upregulates the production of inflammatory mediators. The role of IRAK3 was assessed in rheumatoid arthritis (RA), a disease which is amenable to TNF blockade. As a variant of IRAK3 lacks the death domain required for its canonical role, isoform expression was determined in different inflammatory milieu by immunoblotting. RA synovial explant expression of IRAK3 was measured by qPCR. The expression of the larger, “classical” IRAK3 isoform predominated in macrophages treated with various stimuli. The expression of IRAK3 was higher in RA synovium compared to osteoarthritis synovium. Using collagen-induced arthritis, a murine model of RA, the immunomodulatory role of IRAK3 was investigated with wild-type (WT) and IRAK3-deficient mice expressing the MHC-II A<jats:sup>q</jats:sup> allele. Disease progression was significantly accelerated in IRAK3<jats:sup>−/−</jats:sup> mice. In addition, the circulating levels of IL-1β were greater, and there were fewer Tregs both before and after the onset of disease. Inflammatory gene expression was higher in the arthritic paws of IRAK3<jats:sup>−/−</jats:sup> mice. This study demonstrates that IRAK3 deficiency accelerates the progression of arthritis and increases molecular markers of disease severity.”</jats:p>

Primary Care Resource Utilisation and Costs of Fragility Fractures in Postmenopausal Women in the UK Using CPRD Data Mapped to OMOP Common Data Model

Large Scale Propensity Score Matching With Time-Stratification in Older Women With or Without Fractures in the UK

INCIDENCE OF IMMINENT SUBSEQUENT FRACTURE IN POSTMENOPAUSAL WOMEN AS CAPTURED IN PRIMARY CARE COMPARED TO HOSPITAL RECORDS IN UK AND SPAIN

HOSPITAL RESOURCE UTILIZATION AND COSTS OF IMMINENT SUBSEQUENT FRACTURES IN POSTMENOPAUSAL WOMEN: A DISTRIBUTED NETWORK ANALYSIS USING DATA FROM THE UK AND SPAIN MAPPED TO OMOP COMMON DATA MODEL

Feasibility of a Federated Network Analysis Using Real-World Data Mapped to OMOP Common Data Model to Estimate Healthcare Resource Utilisation and Costs of Imminent Subsequent Fracture

Treatment of Systemic Lupus Erythematosus: Analysis of Treatment Patterns in Adult and Paediatric Patients Across Four European Countries

DARWIN EU®-Trends of Prescription Opioid Use in Europe

Ethnicity data resource in population-wide health records: completeness, coverage and granularity of diversity

COLLATERAL EFFECTS OF THE COVID-19 PANDEMIC ON ENDOCRINE TREATMENTS FOR BREAST AND PROSTATE CANCER IN THE UK: IMPLICATIONS FOR BONE HEALTH

The Risks of Immune-oand Inflammatory Related Post-Acute Sequelae of COVID-19: A Network Study in 6 European Countries, the US, and Korea

Natural History of Dermatomyositis and Polymyositis in Adults and Paediatric Populations: A Network Cohort Study Part of DARWIN EU®

Prevalence of Dermatomyositis and Polymyositis in Adults and Paediatric Populations: A Network Cohort Study Part of DARWIN EU®

Incidence, Prevalence, and Survival of Breast Cancer in the United Kingdom From 2000-2021: A Population-Based Cohort Study

PREDICTING LONG TERM CANCER SURVIVAL FOR HEALTH TECHNOLOGY ASSESSMENT: A MULTINATIONAL COHORT STUDY

Discontinuation of Preventative Treatments in Older People with Complex Health Needs: Self-Controlled Case Series Analyses of Preventable Cardiovascular Events

DISCONTINUATION OF BISPHOSPHONATES IN OLDER PEOPLE WITH COMPLEX HEALTH NEEDS: SELF-CONTROLLED CASE SERIES TO ASSESS FRACTURE RISK

DARWIN EU®-Drug Utilisation Study of Medicines with Prokinetic Properties in Children and Adults Diagnosed with Gastroparesis

DARWIN EU®-Real-World Evaluation of Pulmonary Arterial Hypertension Treatment and Outcomes in Europe

DARWIN EU®-Background Rates of Outcomes of Interest in Patients with Severe Asthma