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Description
Systemic lupus erytematosus (SLE) is an autoimmune disease where the immune system is reactive to self antigens resulting in manifestations like glomerulonephritis and arthritis. The immune system also affects the central nervous system (known as CNS-SLE) leading to neuropsychiatric manifestations such as depression, cognitive impairment, psychosis and seizures. A subset of pathogenic brain-reactive autoantibodies (BRAA) is hypothesized to bind to integral membrane brain proteins, affecting their function, leading to CNS-SLE. I have tested this BRAA hypothesis, using our lupus-mouse model the MRL/lpr mice, and have found it to be a reasonable explanation for some of the manifestations of CNS-SLE. Even when the MRL/lpr had a reduced autoimmune phenotype, their low BRAA sera levels correlated with CNS involvement. The correlation existed between BRAA levels to integral membrane protein and depressive-like behavior. These results were the first to show a correlation between behavioral changes and BRAA levels from brain membrane antigen as oppose to cultured neuronal cells. More accurate means of predicting and diagnosing lupus and CNS-SLE is necessary. Using microarray technology I was able to determine peptide sets that could be predictive and diagnostic of lupus and each specific CNS manifestation. To knowledge no test currently exists that can effectively diagnose lupus and distinguish between each CNS manifestations. Using the peptide sets, I was able to determine possible natural protein biomarkers for each set as well as for five monoclonal BRAA from one MRL/lpr. These biomarkers can provide specific targets for therapy depending on the manifestation. It was necessary to investigate how these BRAA enter the brain. I hypothesized that substance P plays a role in altering the blood-brain barrier (BBB) allowing these BRAA to enter and affect brain function, when bound to its neurokinin-1 receptor (NK-1R). Western blotting results revealed an increase in the levels of NK-1R in the brain of the MRL/lpr compared to the MRL/mp. These MRL/lpr with increased levels of both NK-1R and BRAA displayed CNS dysfunction. Together, these results demonstrate that NK-1R may play a role in CNS manifestations. Overall, the research conducted here, add to the role that BRAA are playing in CNS-lupus.
ContributorsWilliams, Stephanie (Author) / Hoffman, Steven A (Thesis advisor) / Conrad, Cheryl (Committee member) / Chen, Julian (Committee member) / Orchinik, Miles (Committee member) / Arizona State University (Publisher)
Created2011
Description
This dissertation investigates the classification of systemic lupus erythematosus (SLE) in the presence of non-SLE alternatives, while developing novel curve classification methodologies with wide ranging applications. Functional data representations of plasma thermogram measurements and the corresponding derivative curves provide predictors yet to be investigated for SLE identification. Functional nonparametric classifiers form a methodological basis, which is used herein to develop a) the family of ESFuNC segment-wise curve classification algorithms and b) per-pixel ensembles based on logistic regression and fused-LASSO. The proposed methods achieve test set accuracy rates as high as 94.3%, while returning information about regions of the temperature domain that are critical for population discrimination. The undertaken analyses suggest that derivate-based information contributes significantly in improved classification performance relative to recently published studies on SLE plasma thermograms.
ContributorsBuscaglia, Robert, Ph.D (Author) / Kamarianakis, Yiannis (Thesis advisor) / Armbruster, Dieter (Committee member) / Lanchier, Nicholas (Committee member) / McCulloch, Robert (Committee member) / Reiser, Mark R. (Committee member) / Arizona State University (Publisher)
Created2018
Description
Systemic lupus erythematosus (SLE), or lupus, is a rare autoimmune disease in which the antibodies that are formed in the body attack healthy tissues and organs. The most prevalent physical manifestation of the illness is fatigue. Fatigue often plagues patients with no warning and without leaving a trace of measurable evidence. The issue of fatigue’s invisibility and the difficulties of communicating the experience of fatigue has been shown to impact relationships with friends, family, and physicians. It is important for patients to understand their condition in order to better identify their own triggers, manage their condition, and communicate their symptoms to friends, families, and other medical professionals. The study sought to explore the lived experience of women who have lupus, describe the impact of symptom invisibility on social support and patient-doctor relationships, identify effective strategies in communicating and managing the condition, and describe the broad range of life changes associated with the disease. The study utilized in-depth, semi-structured interviews to gather detailed information from eleven women with lupus. Six overarching themes emerged from the data: difficulties with diagnosis, discovering lupus is a process, managing lupus, social impact of lupus, communicating the experience, and limitations of the healthcare system. Symptom invisibility was not frequently cited as the cause of any interpersonal problems faced by the participants. Rather, the results suggest that the current healthcare system in the United States may not be equipped to adequately care for patients with lupus. This study provides insight for recommendations to patients with lupus and may inform cultural and policy changes necessary to improve healthcare delivery.
ContributorsVélez-Bermúdez, Miriam Eunice (Author) / Vargas, Perla A (Thesis advisor) / Mickelson, Kristin D (Committee member) / Roberts, Nicole A. (Committee member) / Arizona State University (Publisher)
Created2016
Description
Systemic Lupus Erythematosus (SLE) is an autoimmune disease resulting in widespread inflammation of various organ tissues including the lung, heart, kidneys, brain, joints, vasculature, and more. Systemic Lupus Erythematosus (SLE) has at present no cure and therefore, treatments focus on improving quality of life by targeting flare-ups of inflammation (6). Diffuse Alveolar Hemorrhage (DAH) is a rare complication of SLE affecting 1-5% of people diagnosed with SLE. DAH is characterized by bleeding into the lung alveolar spaces and is associated with inflammation, potentially caused by infections and injuries. While the prevalence of DAH is low, the mortality rate is high at 50-80% (5). DAH has no proven effective treatment and many treatments used have severe side effects. Serp-1 is a Myxomavirus derived immune modulating serine protease inhibitor, a serpin, with proven efficacy in a wide range of inflammation-associated disorders (1). Due to the efficacy of Serp-1 in reducing arterial inflammation and lung consolidation in mouse herpes virus infections, Serp-1 treatment in a mouse model of pristane-induced DAH was investigated. Multiple groups were tested including mouse models that were not given pristane as well as mice with pristane-induced DAH treated with saline control, wild-type unmodified Serp-1, and a polyethylene glycol-modified variant of Serp-1 termed PEGSerp-1.
ContributorsAliskevich, Emily (Author) / Lucas, Alexandra (Thesis director) / McFadden, Grant (Committee member) / Barrett, The Honors College (Contributor) / School of Human Evolution & Social Change (Contributor) / School of Life Sciences (Contributor)
Created2023-05