926 research outputs found
Inflammatory localized and generalized bone loss in recent-onset rheumatoid arthritis
No full textLems, W.F. [Promotor]Huizinga, T.W.J. [Promotor]Dijkmans, B.A.C. [Promotor]Allaart, C.F. [Copromotor
Immune regulation by mast cells
No full textThe objective of this PhD thesis is to understand mast cell (and basophil) functions and their role in autoimmune disease by focusing on three main aims: 1. To characterize the interaction between innate and Fc receptor triggers on mast cell and basophil function 2. To analyze the interaction between mast cells and CD4+ T cells 3. To understand the function of mast cells in chronic inflammation In this thesis I showed that mast cells can significantly contribute to chronic inflammation through their activation by Fc receptors and TLRs, as well as their interaction with CD4+ T cells, thereby increasing our understanding of their role in allergy and autoimmunity and providing several therapeutic targets to prevent mast cell-mediated immune responses.The work described in this thesis was funded by the Dutch Arthritis Foundation, whom we thank for their support. Additional financial support was obtained from the Dutch Organization for Scientific Research (Vici grant), the Research Foundation Sole Mio, the Leiden Research Foundation (STROL), the Centre for Medical Systems Biology (CMSB) within the framework of the Netherlands Genomics Initiative (NGI), the IMI JU funded project BeTheCure, contract no 115142-2, and European Union (Seventh Framework Programme integrated project Masterswitch; grant Number: 223404). Printing of this thesis was financially supported by the Leiden University Medical Center, Leiden University, and BD Biosciences.UBL - phd migration 201
Determinants of disease course in rheumatoid arthritis
No full textReumatoide arthritis (RA) is een
ernstige, chronische ontstekingsziekte van de gewrichten. Hoofdstuk 1 is
een introductie in epidemiologische gegevens over RA en factoren van
invloed op ziektebeloop.
Hoofdstuk 2 bespreekt de voorspellende waarde van anti-CCP antistoffen
bij patiënten met nog niet te classificeren artritis voor het ontstaan
van RA binnen 3 jaar. Deze antistoffen blijken belangrijke voorspellers
te zijn voor het ontwikkelen van RA bij deze groep patiënten en een
waardevolle aanvulling voor het vroegtijdig stellen van de diagnose RA.
Hoofdstuk 3 onderzoekt de voorspellende waarde van de verdeling van
ontstoken gewrichten bij eerste polibezoek op de ernst van
röntgenologische schade in de toekomst. Artritis van de grote gewrichten
vooral van de knie hangt hiermee samen.
Hoofdstuk 4 analyseert volledige klinische remissie bij patiënten met
RA. In een RA cohort uit Leiden vertoonde 10% blijvende remissie. Deze
patiëntengroep werden gekenmerkt door afwezigheid van antistoffen.
Hoofdstuk 5 beschrijft een gen-omgevingsinteractie tussen roken en de
aanwezigheid van anti-CCP antistoffen bij patiënten met RA die drager
zijn van bepaalde HLA klasse II allelen (de shared epitope allelen).
Hoofdstuk 6 is een theorie over de oorzaak van de afgenomen incidentie
van RA in de afgelopen decennia door een veranderde genetische
samenstelling van de populatie.LEI Universiteit LeidenKlinische evaluatie en behandeling van reumatische ziekte
Anti-citrullinated peptide antibodies in rheumatoid arthritis and undifferentiated arthritis
No full textThe thesis concerns studies on several aspects of the ACPA response in UA and RA patients. One objective was to investigate the effect ACPA on the development of RA and how ACPA and other risk factors could collectively contribute to the development of RA. The second aim was to increase knowledge on the development of the ACPA response itself Chapter 2 is a review on the percentage of patients with UA who develop RA Chapter 3 describes differences and similarities between ACPA-positive and ACPA-negative RA at first presentation to the rheumatologist and after follow-up. The strongest genetic risk factors, SE-alleles, were described to predispose only for ACPA-positive RA. In Chapter 4, it was investigated whether SE is a risk factor for ACPA-positive RA or for the development of ACPA. The contribution of HLA__DRB1 to the development of ACPA-negative RA was investigated in Chapter 5. In Chapter 6, it was determined whether SE-alleles interact with tobaccoexposure in the risk to develop ACPA-positive or ACPA-negative RA and whether different subtypes of SE interact differently with smoking. Chapter 7 evaluates whether tobaccoexposure also influences the isotype of ACPA. Chapters 8 and 9, describe different isotypes and the fine-specificity of the ACPA response. Finally, the results are summarized and discussed.ABBOTT B.V., Bristol-Myers Squibb, het Reumafonds, Roche Nederland B.V., Schering- Plough B.V., Teva Pharma NL en Wyeth Pharmaceuticals B.V.UBL - phd migration 201
Basic disease mechanisms in rheumatoid arthritis
No full textRheumatoid Arthritis (RA) is a chronic inflammatory disorder that typically affects cartilage and bone of small and middle-sized joints. Infiltration of the synovium by inflammatory cells causes destruction of cartilage, erosion of the adjacent bone and ultimately loss of function of the affected joint. Systemic inflammation, often going in parallel, can affect several organs and has long-term impact on organ function. This thesis presents work that investigates several aspects of basic immunological disease mechanisms with relevance to the inflammatory immune response in RA. Specifically, three main research questions triggered the experiments presented and form the outline of this thesis: 1. Do regulatory T cells feature anti-inflammatory properties besides the inhibition of effector T cells, which could help explain their therapeutic effectiveness in a murine model of established arthritis? 2. Are there specific features of the immune response to citrullinated antigens that could contribute to inflammation in RA, and can analysis of these features help in understanding the characteristics of anti citrullinated protein antibody producing B cells and their development? 3. Do certain genetic variants that associate with RA susceptibility contribute also to disease progression, as evidenced by the rate of joint destruction in RA?Dutch Arthritis Foundation (het Reumafonds), UCB, Roche, Thermo Fisher Scientific, MSD, AbbVie, Euro Diag- nostica, Teva, Pfizer.UBL - phd migration 201
TNF blockade in daily practice
No full textIn conclusion, this thesis describes different clinical aspects on the use of anti-TNF. Initial combination treatment with infliximab and methotrexate seems very promising in early RA and may even alter the course of the disease. In patients with intolerance or inadequate response to infliximab, a second TNF-blocking agent can be successful, although, the introduction of new biologicals such as rituximab and abatacept provides other therapeutic options. Further research is needed to answer the question which drugs are indicated after failing a first TNF-blocking agent, or even as initial therapy. The use of intra-articular infliximab is inferior to intra-articular depomedrol in chronic and/or recurrent gonartrtitis and this expensive treatment should not have benefit of the doubt in these patients. In contrast, the use of infliximab in rheumatoid vasculitis seems promising in patients who have contra-indication for the recommended immunosupression. Influenza- and pneumococcal vaccinations result in less and lower antibody titers during treatment with anti-TNF, however, antibodies were formed and it remains unclear whether the lower laboratory outcomes are clinically relevant. To date, most guidelines recommend vaccination in patients using immunosuppressive therapy. During the use of anti-TNF neurological symptoms comparable to those of multiple sclerosis (MS) have been described and MR changes have been detected. The use of anti-TNF should be considered as contra-indicated in patients with signs and symptoms compatible with MS.Shering-Plough BV, Teva Pharma Nederland BV, Wyeth Pharmaceuticals BV, Abbott BV, Roche Nederland BV, UCB Pharma BV, Bristol-Myers Squibb BV, Sanofi-Aventis Netherlands BV, ,Pfizer BVUBL - phd migration 201
Dentritic cells and the battle against arthritis
No full textIn a murine model for rheumatoid arthritis, we wished to investigated whether it was possible to skew the immune response with a cellular vaccin to protect the mice against the induction and/or progeression of arthritis. the model that was used for this purpose was Collagen-Induced Arthritis (CIA). As dendritic cells (DCs) are the main antigen-presenting cells and key players in setting immune responses and connecting innate witth adaptive immunity, it is favorable to use these cells to manipulate the immune system to circumvent autoimmunity, in this case CIA. Because CIA is still implicated as a Th1-mediated disease, the aim was to skew the immune system towards a more Th2-like phenotype or to induce a T cell with a regulatory capacity. Therefore, several ways to stimulate DCs and subsequently the evolving T cell response were selected, to analyze whether Th2 cells or regulatory T cells were activated, resulting in the inhibition of arthritis.LEI Universiteit LeidenReumafonds (Dutch Arthritis Association)
J.E. Jurriaanse StichtingKlinische evaluatie en behandeling van reumatische ziekte
Treatment of early rheumatoid and undifferentiated arthritis
No full textThis thesis focuses on different aspects of treatment of patients with rheumatoid arthritis (RA) and undifferentiated arthritis (UA), based on the results of three intervention studies; the IMPROVED-study, the BeSt study and the PROMPT study. This thesis discusses the results of different treatment strategies for patients with RA and UA; the percentage of patients that achieves remission , the mean disease activity, radiographic damage progression and daily functioning. I then analysed the factors that effect the response to treatment and the achievement of drug free remission . Then radiological damage progression is discussed. Are there patients with early arthritis who have rapid radiographic progression in the first year after diagnosis or we can prevent this with effective treatment? We also assessed whether patients with early RA have metacarpal bone mineral density loss after 4 months, measured with digital X-ray radiogrammetry, and whether this predicts radiological damage progression after 1 year of anti-rheumatic treatment. Finally , I analyzed how the IMPROVED population was doing with regard to psychological well-being (mood and optimism), quality of life and the relationship of these so-called patient-reported outcomes with disease activity and achievement of remission.The research was financially supported by AbbVie, the Dutch Arthritis Foundation, the Netherlands Organisation for Scientific Research, the Dutch College for Health Insurances, Janssen Biologics B.V. and Schering-Plough B.V. The publication of this thesis was financially supported by the Dutch Arthritis Foundation (Reumafonds), AbbVie B.V., Pfizer B.V., Roche B.V. and UCB Pharma B.V.UBL - phd migration 201
Comprehensive care in systemic sclerosis
No full textPatients with Systemic Sclerosis have to cope with an uncertain disease course, varying impact on physical functioning and limited treatment options. There is increasing acknowledgement of the psychological burden that this entails, however, from a medical point of view, the impact of a disease is often expressed as a degree of physical disability . The International Classification of Functioning ( ICF ) WHO describes the functioning of people, but also the factors that affect functioning; the patient is placed central, and the following adherent domains are described: a) disease characteristics (body functions and structures), b ) activities and social participation , c ) contextual factors (available treatment) and d ) personal characteristics of patients. The aim of this thesis was to gain more insight into the impact of SSc on the health of patients with respect the ICF classification. The thesis includes a study of health care need, as well as the influence of systemic sclerosis in oral function, sexual function, hand function, impact of the disease on work status. Also a echogrdiographic technique named speckle tracking strain analysis, evaluating left ventricular function was studied. Finally, a multidisciplinary rehabilitation program was evaluated using an RCT .NVLE Actelion PharmaceuticalsUBL - phd migration 201
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