The clinical manifestations and outcomes of systemic lupus erythematosus (SLE) are remarkably heterogeneous. In this thesis, issues relating to the diagnosis and prognosis of SLE were studied,... Show moreThe clinical manifestations and outcomes of systemic lupus erythematosus (SLE) are remarkably heterogeneous. In this thesis, issues relating to the diagnosis and prognosis of SLE were studied, focussing on the application of histopathologic evaluation in conjunction with clinical features in the setting of lupus nephritis (LN) and neuropsychiatric SLE (NP-SLE). In the first part, we demonstrated that classification criteria for SLE cannot be unequivocally applied to patients from nephrology clinics who present with full house glomerular deposits suggestive of LN/SLE. The patients with full house glomerular deposits without clinical SLE represented a distinct entity with a remarkably poor renal outcome. In the second part, clinical and histopathologic determinants of renal outcome were investigated to improve prognostication in LN. First, we identified a subgroup of patients with class III/IV LN with favourable renal outcome indicating that the current classification warrants refinement. Next, we identified prognosticators that may add to the current histopathologic classification of LN. The last part of this thesis was focused on the aetiopathogenesis of SLE, in which the complement system was identified as an important player and thereby therapeutic target in neuropsychiatric lupus and in which pregnancy-acquired microchimerism in relation to the occurrence of SLE was further investigated. Show less
Rheumtaoid Arthritis (RA) is an autoimmune disease characterized by extensive inflammation of synovial joints. RA patients can be subdivided in two distinct disease subsets based on the presence of... Show moreRheumtaoid Arthritis (RA) is an autoimmune disease characterized by extensive inflammation of synovial joints. RA patients can be subdivided in two distinct disease subsets based on the presence of anti-citrullinated protein antibodies (ACPA). The HLA locus is the most important risk factor for ACPA-positive RA. In this thesis we investigate the association between HLA, Rheumatoid Arthritis and ACPA and provide a molecular basis for this assocation. Show less
The development of outcome measures in the field of rheumatology has shown a rapid and constructive advance in the last decades. It has been achieved to obtain more uniformity in the evaluation of... Show moreThe development of outcome measures in the field of rheumatology has shown a rapid and constructive advance in the last decades. It has been achieved to obtain more uniformity in the evaluation of inflammatory rheumatic disorders, especially concerning long-term outcomes and disease activity assessments. In the field of rheumatoid arthritis, clinical experts and researchers have done a lot of work under the umbrella of OMERACT (Outcome Measures in Rheumatology Clinical Trials). In the field of ankylosing spondylitis, major advances in the outcome and therapeutic advances in the last years have been possible because of projects piloted within ASAS (the Assessment of Spondyloarthritis international Society). The analyses and studies presented in this thesis were part of this process, with most of the work performed in international working groups under auspices of either OMERACT or ASAS or both. In rheumatoid arthritis, a detailed insight into radiographic scores was conducted (Sharp van der Heijde score, SENS). Performances of automated methods for measuring measurement of joint space narrowing were assessed. The delay to first specific treatment in early rheumatoid arthritis was also analyzed, and its impact on radiographic outcome was evaluated. In ankylosing spondylitis, three different methods aiming at scoring activity of the disease on MRI of the spine were compared, and a new disease activity score was developed (ASDAS). Show less
This thesis discusses several aspects of therapeutic interventions for arthritis of the knee, especially arthroscopic lavage. Arthroscopic lavage is a technique in which the inflamed knee of the... Show moreThis thesis discusses several aspects of therapeutic interventions for arthritis of the knee, especially arthroscopic lavage. Arthroscopic lavage is a technique in which the inflamed knee of the patient is rinced with saline. After the procedure corticosteroids can be administered to suppress inflammation. Arthroscopic lavage was superior in suppressing recurrence of arthritis compared to standard joint injections with corticosteroids. The occurence of fibrosis in the inflamed joint was predictive of an inferior response. During arthroscopic lavage synovial tissue samples can be obtained. These biopsies were studied before and after treatment with anti-TNF in longstanding and early (therapy-naieve) Rheumatoid Arthritis (RA)patients. The clinical and synovial effect were comparable between both groups. In the latter part differences in synovial inflamation between RA patients with and without antibodies against cyclic citrullinated peptides (CCP) are discussed in relation to the occurence of joint damage. In anti-CCP positive patients we found more infiltrating lymphocytes leading to progression of joint damage. Also, temporal changes in synovial inflammation differed between anti-CCP positive and anti_CCP negative RA, underlining the fenotypical differences betwen both disease entities. Show less
