Lipid signaling is an essential biological event/process in a plethora of pathophysiological conditions. The underlying idea of this thesis is that many of the roles and the complex interplay of... Show moreLipid signaling is an essential biological event/process in a plethora of pathophysiological conditions. The underlying idea of this thesis is that many of the roles and the complex interplay of the individual signaling lipids in inflammatory processes and related conditions in health and disease is not well known, and therefore has to be studied integrally as a complex network. In order to study this complex interplay, an improved broad analytical method is necessary to analyze a wide range of different signaling lipid classes such as oxylipins, (nitro) free fatty acids, endocannabinoids, bile acids and different subclasses of lysophospholipids. Therefore, the aim of this thesis is to develop a better method to study signaling lipids, and to apply it to study the role of these molecules in several relevant biological questions for a better understanding of inflammation related pathophysiology including autoimmune diseases, neurodegeneration and regulatory effect of exercise training. Show less
ackgroundRheumatoid arthritis (RA) is a chronic autoimmune disease for which prediction of long-term prognosis from disease’s outset is not clinically feasible. The importance of immunoglobulin G ... Show moreackgroundRheumatoid arthritis (RA) is a chronic autoimmune disease for which prediction of long-term prognosis from disease’s outset is not clinically feasible. The importance of immunoglobulin G (IgG) and its Fc N-glycosylation in inflammation is well-known and studies described its relevance for several autoimmune diseases, including RA. Herein we assessed the association between IgG N-glycoforms and disease prognosis at 2 years in an early inflammatory arthritis cohort.MethodsSera from 118 patients with early inflammatory arthritis naïve to treatment sampled at baseline were used to obtain IgG Fc glycopeptides, which were then analyzed in a subclass-specific manner by liquid chromatography coupled to mass spectrometry (LC-MS). Patients were prospectively followed and a favorable prognosis at 2 years was assessed by a combined index as remission or low disease activity (DAS28 < 3.2) and normal functionality (HAQ ≤ 0.25) while on treatment with conventional synthetic DMARDs and never used biologic DMARDs.ResultsWe observed a significant association between high levels of IgG2/3 Fc galactosylation (effect 0.627 and adjusted p value 0.036 for the fully galactosylated glycoform H5N4F1; effect −0.551 and adjusted p value 0.04963 for the agalactosylated H3N4F1) and favorable outcome after 2 years of treatment. The inclusion of IgG glycoprofiling in a multivariate analysis to predict the outcome (with HAQ, DAS28, RF, and ACPA included in the model) did not improve the prognostic performance of the model.ConclusionPending confirmation of these findings in larger cohorts, IgG glycosylation levels could be used as a prognostic marker in early arthritis, to overcome the limitations of the current prognostic tools. Show less
Metsios, G.S.; Moe, R.H.; Esch, M. van der; Zanten, J.J.C.S.V. van; Fenton, S.A.M.; Koutedakis, Y.; ... ; IMPACT-RMD Consortium 2019
Cardiovascular disease (CVD) morbidity and mortality is highly prevalent in patients with rheumatoid arthritis (RA) with debilitating effects for the individual as well as significant healthcare... Show moreCardiovascular disease (CVD) morbidity and mortality is highly prevalent in patients with rheumatoid arthritis (RA) with debilitating effects for the individual as well as significant healthcare impact. Current evidence demonstrates that engaging in aerobic and resistance exercise (i.e. structured physical activity) can significantly improve patient-reported and clinical index-assessed outcomes in RA. In addition to this, engagement in exercise programmes improves, in a dose-dependent manner, the risk of developing CVD as well as CVD symptoms and outcomes. The present narrative review uses evidence from systematic reviews and meta-analyses as well as controlled trials, to synthesize the current state-of-the-art on the potential effects of aerobic and resistance exercise on CVD risk factors as well as on cardiac and vascular function and structure in people with RA. Where there is a lack of evidence in RA to explain potential mechanisms, relevant studies from the general population are also discussed and linked to RA. Show less
Aizenberg, E.; Shamonin, D.P.; Reijnierse, M.; Helm-van Mil, A.H.M. van der; Stoel, B.C. 2019
This thesis focussed on inflammation observed on magnetic resonance imaging (MRI) in the early phases of rheumatoid arthritis (RA) and was divided into two parts. In the first part we explored the... Show moreThis thesis focussed on inflammation observed on magnetic resonance imaging (MRI) in the early phases of rheumatoid arthritis (RA) and was divided into two parts. In the first part we explored the prevalence of inflammation and erosions detected on MRI in the general population. In the second part, we studied the early phases of RA and assessed factors which could be associated with radiographic joint damage or local inflammation detected on MRI. Show less
This thesis is two-fold focused on rheumatoid arthritis and axial spondyloarthritis. It covers outstanding aspects of research methodology in the assessment of inflammation and damage in patients... Show moreThis thesis is two-fold focused on rheumatoid arthritis and axial spondyloarthritis. It covers outstanding aspects of research methodology in the assessment of inflammation and damage in patients with these diseases. The studies pertaining to the first part of the thesis focus on rheumatoid arthritis and may help to better understand the relationship between disease activity, radiographic damage and disability. More specifically, they evaluate which of the available tools (individual instruments or composite indices) is associated with radiographic damage and which of the different types of structural lesions detectable on radiographs is associated with disability. Additionally, these studies address methodological issues related to the optimal assessment of radiographic progression in clinical trials. The studies described in the second part of the thesis evaluate the benefit of supplementary tests reflecting inflammation, especially to help classifying (diagnosing) patients and to monitor disease activity. Among others, the studies described in this thesis provide data that allow a better usage of these tests in clinical practice. Overall, this thesis provide guidelines on how to assess properly rheumatoid arthritis and axial spondyloarthritis in clinical trials and in clinical practice. This precise way of assessment will lead to a better understanding and a better management of these diseases. Show less
Woude, D. van der; Toes, R.E.M.; Scherer, H.U. 2014
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... Show moreThis 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 humans Show less
