Lic.-avh. (sammanfattning) Stockholm : Karolinska institutet, 2008. / Härtill 2 uppsatser.

Thesis (Ph. D.)--University of Washington, 2002. / Vita. Includes bibliographical references (leaves 102-108).

published_or_final_version / Dentistry / Master / Master of Dental Surgery

published_or_final_version / Orthopaedics and Traumatology / Master / Master of Medical Sciences

Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation and subsequent destruction of synovial joints. Although its causes remain largely unknown, a substantial genetic contribution is known to exist. During the last decades the benefits of early aggressive treatment have become evident, and more potent therapeutic options have become available. These advances have increased the demands for rapid accurate diagnosis and prognostic markers of disease course and therapy response. The ‘rheumatoid factor’ (RF) has long been used as a diagnostic and prognostic marker of RA. In this thesis, the utility of measuring antibodies to cyclic citrullinated peptides (CCP) was investigated. In a population-based arthritis incidence study, 69 very early arthritis patients (symptom duration < 3 months) were identified. The anti-CCP test, performed at baseline and related to diagnosis at the 2-year follow-up, had a diagnostic specificity for RA of 96% and a sensitivity of 44%, both of which were superior to RF. In a prospective cohort of 242 incident cases of RA (symptom duration < 1 year), 64% of the patients tested positive for anti-CCP at baseline (equal to RF). Despite receiving more active anti-rheumatic therapy, the anti-CCP-positive patients had a more aggressive disease course during 3 years as compared to those testing negative. The 158VV genotype of Fcγ Receptor type IIIA (FcγRIIIA), which binds IgG with higher affinity than 158FF, was associated with an increased susceptibility to RA in men, but not in women. Previous studies report conflicting results, and none stratified according to gender. The 158V/F polymorphism of FcγRIIIA was not found to influence outcome of anti-tumour necrosis factor therapy in 282 RA patients, contradicting hints from previous studies. Genetic variation in proteins of the inflammasome, an interleukin-1 (IL-1) regulating intracellular protein complex, is associated with rare autoinflammatory conditions and possibly with Crohn’s disease. In this first study on genetic variation of the inflammasome in RA, we describe a compound polymorphism of the genes CIAS1 and TUCAN that associates both with susceptibility to RA and to the severity of the disease. Hypothetically, these genes may identify a subgroup of RA patients that would benefit from anti-IL-1 therapy. This thesis work emphasizes the benefits of testing for anti-CCP in the diagnosis and outcome prediction in early arthritis. FcγRIIIA genotype is likely to affect RA susceptibility and further work should apply a gender perspective. Inflammasome genetics may influence the risk of developing RA. Additional studies are warranted to settle whether it also identifies a subgroup of RA patients benefiting from IL-1 targeted therapy.

published_or_final_version / Medical Sciences / Master / Master of Medical Sciences

No description available.

Engaging in 150+ minutes of moderate to vigorous exercise is a recommended self-management strategy for arthritis. Considering the low levels of exercise among individuals with arthritis, national calls have been made for investigation of theory-based processes important for adherence. Self-regulation may be a key process important for persisting with exercise plans in the face of arthritis pain anxiety. The present study examined relationships based upon a known model (Fear Avoidance [FA] model) used to understand self-regulatory behavioral responses to pain anxiety – an unexamined relationship in the arthritis and exercise literature. Primary study purposes involved examination of predictors (pain, pain anxiety, and pain acceptance) of maladaptive and adaptive self-regulatory responses among adults with arthritis who exercise. The secondary purpose examined whether participants who met the recommended dose of exercise over a two-week period significantly differed in their pain cognitions and self-regulatory responses to pain anxiety compared to less active counterparts. Participants were 136 adults (Mage = 49.75 ± 13.88years) with self-reported medically-diagnosed arthritis. Online surveys of pain cognitions and demographics were completed at baseline, followed by self-reported exercise two weeks later. Hierarchical multiple regression analyses illustrated that: (a) pain anxiety was a significant, positive predictor of the use of maladaptive self- regulatory responses (p < .001) and (b) the interaction of pain anxiety x pain acceptance was a significant predictor of the adaptive self-regulatory responses relationship (p < .05). Follow-up analyses illustrated that pain acceptance was a moderator of the pain anxiety – adaptive self-regulatory responses relationship. Participants with higher pain acceptance used adaptive responses less frequently when anxiety was lower than participants with lower acceptance. When pain anxiety was higher, both higher and lower pain acceptance was associated with the more frequent use of adaptive self-regulatory responses. A MANOVA analysis illustrated that participants meeting the recommended exercise dose had significantly lower pain anxiety, higher pain acceptance, and used maladaptive self-regulatory responses less compared to the group not meeting the dose (p’s ≤ .01). Taken together, findings provide the first ever support for FA model predictions in the arthritis – exercise domain. The results of this observational study suggest a next step could be an extended longitudinal study design with multiple time periods of assessment (e.g., measures once a month over a six-month period). Observing the relationships over time would provide a better understanding of within-person changes in the psychosocial variables relative to exercise. Such research would provide a profile of individuals’ levels of anxiety, acceptance, and self-regulatory responses when they either decrease or completely avoid exercise and when they adhere. Obtaining a social cognitive profile of people at risk for exercise avoidance may be a useful tool in the future to identify those who are in need of intervention to deal with their pain anxiety.

No description available.

No description available.