Adipose tissue inflammation : implications for joint diseases

This thesis investigates the role of adipose tissue inflammation in joint diseases such as osteoarthritis (OA) and rheumatoid arthritis (RA) . In the first part, we show that baseline levels of circulating adiponectin can predict radiographic progression in patients with early RA. In contrast, in patients with hand OA, this association appears protective. Therefore, to obtain insight into the mechanisms underlying these associations, we investigated the high-molecular-weight isoform of adiponectin (hmwAPN), which is one of the most biologically active isoforms of adiponectin. We show that the associations of total adiponectin with radiographic progression are not mediated by hmwAPN, in either RA or HOA. In the second part, we present the immunological characterization of the infrapatellar fat pad (IFP), a joint associated adipose tissue, in patients with advanced knee OA. We observed profound differences in secreted inflammatory factors and immune cell composition between the IFP and paired subcutaneous adipose tissue samples. Interestingly, we observed obesity-related changes in the IFP phenotype, and in macrophages and adipocytes, Therefore, we investigated the modulatory effects of adipocytes on the phenotype of human macrophages in vitro and we observed that adipocyte-derived lipids can mediate the obesity-related changes in the phenotype of adipose tissue macrophages in humansRoche BD biosciencesUBL - phd migration 201

Do high molecular weight adiponectin levels associate with radiographic progression in early rheumatiod arthritis and hand osteoarthritis?

Pathophysiology and treatment of rheumatic disease

Update on the treatment of nonsystemic juvenile idiopathic arthritis including treatment-to-target: is (drug-free) inactive disease already possible?

Purpose of review This review concerns the outcome for nonsystemic juvenile idiopathic arthritis (JIA) with emphasis on treatment-to-target (T2T) and treatment strategies aiming at inactive disease by giving an overview of recent articles. Recent findings More efficacious therapies and treatment strategies/T2T with inactive disease as target, have improved the outcome for JIA significantly. Recent studies regarding treatment strategies have shown 47-68% inactive disease after 1 year. Moreover, probability of attaining inactive disease at least once in the first year seems even higher in recent cohort-studies, reaching 80%, although these studies included relatively high numbers of oligoarticular JIA patients. However, 26-76% of patients flare upon therapy withdrawal and prediction of flares is still difficult. Remission can be achieved and sustained in (some) JIA patients, regardless of initial treatment. Cornerstone principles in the management of nonsystemic JIA treatment are early start of DMARD therapy, striving for inactive disease and T2T by close and repeated monitoring of disease activity. T2T and tight control appear to be more important than a specific drug in JIA. Next to inactive disease, it is important that patients/parents are involved in personal targets, like reduction of pain and fatigue. Future studies should focus on predictors (based on imaging-methods or biomarkers) for sustained drug-free remission and flare.Transplantation and immunomodulatio

Inflammatory features of infrapatellar fat pad in rheumatoid arthritis versus osteoarthritis reveal mostly qualitative differences

Clinical epidemiolog

ADIPONECTIN IS A PREDICTOR FOR RADIOGRAPHIC PROGRESSION IN EARLY RA PATIENTS, INDEPENDENTLY OF ANTI-CCP ANTIBODIES

Pathophysiology and treatment of rheumatic disease

Are Baseline High Molecular Weight Adiponectin Levels Associated with Radiographic Progression in Rheumatoid Arthritis and Osteoarthritis?

Pathophysiology and treatment of rheumatic disease

Baseline Serum Adipokine Levels Predict Radiographic Progression in Early Rheumatoid Arthritis

Objective. Adipose tissue can secrete soluble mediators (adipokines) with potent immune regulatory functions. Some adipokines have been previously associated with radiographic damage in patients with rheumatoid arthritis (RA). In the present study, we investigated the capacity of baseline adipokine levels to predict radiographic progression over a period of 4 years and studied their contribution relative to that of other known risk factors, such as anti-cyclic citrullinated peptide (anti-CCP) antibodies. Methods. Serum concentrations of leptin, visfatin, resistin, adiponectin, adipsin, tumor necrosis factor alpha (TNF alpha), and interleukin-6 (IL-6) were determined in serum samples obtained at baseline from 253 patients with RA from the Early Arthritis Cohort. The association between levels of these adipokines and radiographic progression was determined using a multivariate normal regression model correcting for age, sex, treatment strategy, body mass index (BMI), and the presence of anti-CCP antibodies. Results. Levels of IL-6, TNF alpha, visfatin, and adiponectin were positively associated with radiographic progression over 4 years. This association was independent of BMI. However, only adiponectin levels remained significantly associated with radiographic progression when the model was corrected for the presence of anti-CCP antibodies, whereas a trend was observed for IL-6. The association of both TNF alpha and visfatin with radiographic damage disappeared after correction for the presence of anti-CCP antibodies, which is consistent with the fact that the levels of both cytokines correlated significantly with anti-CCP antibody levels in these patients. Conclusion. Our results indicate that adipokines are predictors of radiographic progression in RA, possibly through distinct underlying biologic mechanisms.Pathophysiology and treatment of rheumatic disease

THE INFRAPATELLAR FAT PAD OF OSTEOARTHRITIC PATIENTS HAS AN INFLAMMATORY PHENOTYPE

Pathophysiology and treatment of rheumatic disease

Inflammatory Cells in Patients with Endstage Knee Osteoarthritis: A Comparison between the Synovium and the Infrapatellar Fat Pad

Conclusion. Our data suggest that the immune cell composition of the synovium and the IFP is similar, and includes activated cells that could contribute to inflammation through secretion of proinflammatory cytokines. Moreover, preliminary analyses indicate that synovial CD4+ T cells might associate with pain in patients with endstage OA of the knee.Optimising joint reconstruction management in arthritis and bone tumour patient