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
The 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... Show moreThe 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. Show less
The aim of this thesis was to unravel the role of the humoral immune system in rheumatoid arthritis patients by employing new immunosuppressive strategies, i.e. specific B-cell depletion with... Show moreThe aim of this thesis was to unravel the role of the humoral immune system in rheumatoid arthritis patients by employing new immunosuppressive strategies, i.e. specific B-cell depletion with Rituximab and non-specific lymfoablative treatment with high dose chemotherapy and hematopoeietic stem cell transplantation. This thesis evaluates the clinical benefit of these strategies as well as the immunological changes that coincide with clinical improvement. By combining clinical outcome with immunological parameters of the humoral immune system, these studies provide a unique approach to investigatepathologic mechanisms in rheumatoid arthritis. Show less
