Browsing by Subject "Arthritis, Rheumatoid"
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Item Open Access A novel inflammatory biomarker, GlycA, associates with disease activity in rheumatoid arthritis and cardio-metabolic risk in BMI-matched controls.(Arthritis Res Ther, 2016-04-12) Bartlett, David B; Connelly, Margery A; AbouAssi, Hiba; Bateman, Lori A; Tune, K Noelle; Huebner, Janet L; Kraus, Virginia B; Winegar, Deborah A; Otvos, James D; Kraus, William E; Huffman, Kim MBACKGROUND: RA and CVD both have inflammation as part of the underlying biology. Our objective was to explore the relationships of GlycA, a measure of glycosylated acute phase proteins, with inflammation and cardiometabolic risk in RA, and explore whether these relationships were similar to those for persons without RA. METHODS: Plasma GlycA was determined for 50 individuals with mild-moderate RA disease activity and 39 controls matched for age, gender, and body mass index (BMI). Regression analyses were performed to assess relationships between GlycA and important markers of traditional inflammation and cardio-metabolic health: inflammatory cytokines, disease activity, measures of adiposity and insulin resistance. RESULTS: On average, RA activity was low (DAS-28 = 3.0 ± 1.4). Traditional inflammatory markers, ESR, hsCRP, IL-1β, IL-6, IL-18 and TNF-α were greater in RA versus controls (P < 0.05 for all). GlycA concentrations were significantly elevated in RA versus controls (P = 0.036). In RA, greater GlycA associated with disease activity (DAS-28; RDAS-28 = 0.5) and inflammation (RESR = 0.7, RhsCRP = 0.7, RIL-6 = 0.3: P < 0.05 for all); in BMI-matched controls, these inflammatory associations were absent or weaker (hsCRP), but GlycA was related to IL-18 (RhsCRP = 0.3, RIL-18 = 0.4: P < 0.05). In RA, greater GlycA associated with more total abdominal adiposity and less muscle density (Rabdominal-adiposity = 0.3, Rmuscle-density = -0.3, P < 0.05 for both). In BMI-matched controls, GlycA associated with more cardio-metabolic markers: BMI, waist circumference, adiposity measures and insulin resistance (R = 0.3-0.6, P < 0.05 for all). CONCLUSIONS: GlycA provides an integrated measure of inflammation with contributions from traditional inflammatory markers and cardio-metabolic sources, dominated by inflammatory markers in persons with RA and cardio-metabolic factors in those without.Item Open Access B cells in rheumatoid synovitis.(Arthritis Res Ther, 2005) Weyand, Cornelia M; Seyler, Thorsten M; Goronzy, Jörg JIn rheumatoid arthritis, T cells, B cells, macrophages, and dendritic cells invade the synovial membranes, establishing complex microstructures that promote inflammatory/tissue destructive lesions. B cell involvement has been considered to be limited to autoantibody production. However, recent studies suggest that B cells support rheumatoid disease through other mechanisms. A critical element of rheumatoid synovitis is the process of ectopic lymphoid neogenesis, with highly efficient lymphoid architectures established in a nonlymphoid tissue site. Rheumatoid synovitis recapitulates the pathways of lymph node formation, and B cells play a key role in this process. Furthermore, studies of rheumatoid lesions implanted in immunodeficient mice suggest that T cell activation in synovitis is B cell dependent, indicating the role played by B cells in presenting antigens and providing survival signals.Item Open Access Chronic Lyme disease: the controversies and the science.(Expert Rev Anti Infect Ther, 2011-07) Lantos, Paul MThe diagnosis of chronic Lyme disease has been embroiled in controversy for many years. This is exacerbated by the lack of a clinical or microbiologic definition, and the commonality of chronic symptoms in the general population. An accumulating body of evidence suggests that Lyme disease is the appropriate diagnosis for only a minority of patients in whom it is suspected. In prospective studies of Lyme disease, very few patients go on to have a chronic syndrome dominated by subjective complaints. There is no systematic evidence that Borrelia burgdorferi, the etiology of Lyme disease, can be identified in patients with chronic symptoms following treated Lyme disease. Multiple prospective trials have revealed that prolonged courses of antibiotics neither prevent nor alleviate such post-Lyme syndromes. Extended courses of intravenous antibiotics have resulted in severe adverse events, which in light of their lack of efficacy, make them contraindicated.Item Open Access Rheumatoid arthritis T cell and muscle oxidative metabolism associate with exercise-induced changes in cardiorespiratory fitness.(Scientific reports, 2022-05) Andonian, Brian J; Koss, Alec; Koves, Timothy R; Hauser, Elizabeth R; Hubal, Monica J; Pober, David M; Lord, Janet M; MacIver, Nancie J; St Clair, E William; Muoio, Deborah M; Kraus, William E; Bartlett, David B; Huffman, Kim MRheumatoid arthritis (RA) T cells drive autoimmune features via metabolic reprogramming that reduces oxidative metabolism. Exercise training improves cardiorespiratory fitness (i.e., systemic oxidative metabolism) and thus may impact RA T cell oxidative metabolic function. In this pilot study of RA participants, we took advantage of heterogeneous responses to a high-intensity interval training (HIIT) exercise program to identify relationships between improvements in cardiorespiratory fitness with changes in peripheral T cell and skeletal muscle oxidative metabolism. In 12 previously sedentary persons with seropositive RA, maximal cardiopulmonary exercise tests, fasting blood, and vastus lateralis biopsies were obtained before and after 10 weeks of HIIT. Following HIIT, improvements in RA cardiorespiratory fitness were associated with changes in RA CD4 + T cell basal and maximal respiration and skeletal muscle carnitine acetyltransferase (CrAT) enzyme activity. Further, changes in CD4 + T cell respiration were associated with changes in naïve CD4 + CCR7 + CD45RA + T cells, muscle CrAT, and muscle medium-chain acylcarnitines and fat oxidation gene expression profiles. In summary, modulation of cardiorespiratory fitness and molecular markers of skeletal muscle oxidative metabolism during exercise training paralleled changes in T cell metabolism. Exercise training that improves RA cardiorespiratory fitness may therefore be valuable in managing pathologically related immune and muscle dysfunction.Trial registration: ClinicalTrials.gov, NCT02528344. Registered on 19 August 2015.Item Open Access Robust test method for time-course microarray experiments.(BMC Bioinformatics, 2010-07-22) Sohn, Insuk; Owzar, Kouros; George, Stephen L; Kim, Sujong; Jung, Sin-HoBACKGROUND: In a time-course microarray experiment, the expression level for each gene is observed across a number of time-points in order to characterize the temporal trajectories of the gene-expression profiles. For many of these experiments, the scientific aim is the identification of genes for which the trajectories depend on an experimental or phenotypic factor. There is an extensive recent body of literature on statistical methodology for addressing this analytical problem. Most of the existing methods are based on estimating the time-course trajectories using parametric or non-parametric mean regression methods. The sensitivity of these regression methods to outliers, an issue that is well documented in the statistical literature, should be of concern when analyzing microarray data. RESULTS: In this paper, we propose a robust testing method for identifying genes whose expression time profiles depend on a factor. Furthermore, we propose a multiple testing procedure to adjust for multiplicity. CONCLUSIONS: Through an extensive simulation study, we will illustrate the performance of our method. Finally, we will report the results from applying our method to a case study and discussing potential extensions.Item Open Access Self-Efficacy and Adherence Behaviors in Rheumatoid Arthritis Patients.(Preventing chronic disease, 2018-10) Oshotse, Christiana; Zullig, Leah L; Bosworth, Hayden B; Tu, Pikuei; Lin, CherylIntroduction
Rheumatoid arthritis (RA) is a common disease that requires patient self-management with chronic medications. Adherence rates for RA medications are suboptimal. This study explores medication adherence and self-efficacy behaviors among RA patients.Methods
We conducted a qualitative study comprising focus groups and individual interviews. Nineteen participants were recruited and screened to participate in three 90-minute focus groups (n = 13) and six 60-minute individual interviews. We created and maintained a codebook to analyze data. Interviews were analyzed by using NViVo qualitative analysis software.Results
Key points in participant interviews were 1) self-efficacy as influenced by the ability to establish routines, and having an understanding relationship with their healthcare provider; 2) self-efficacy to adjust medications depended on having permission from providers to adjust medications, perceptions of the effectiveness of medications, and confidence in self-knowledge to make appropriate adjustments; and 3) changes in self-efficacy over time were influenced by initial denial and later acceptance of the diagnosis. Participant interviews revealed that medication adherence is a spectrum that ranges from adherent to nonadherent.Conclusion
Participants' experience with RA medications revealed varied underlying reasons for adherence behaviors. Recognizing adherence as a dynamic behavior has important implications for how adherence interventions are designed. For example, participants reported adjusting medications in response to the unpredictable nature of RA. Interventions could collect information about RA symptoms and be tailored to provide adherence support at times when patients need it most. The importance of self-efficacy in influencing participants' adherence behaviors is an area for continuing research among patients and providers.