Systemic lupus erythematosus (SLE) is a complex autoimmune disease. Genetic factors playing an important role in disease susceptibility have long been suggested. Transforming growth factor-beta (TGF-beta) regulates differentiation and proliferation of T cells. Therefore, it could be a candidate gene for the development of systemic lupus erythematosus. Allelic polymorphisms in TGF-beta promoter region (-988, -800, -509) and in exon 1 (codon 10 and codon 25) have been suggested to associate with SLE susceptibility. Allelic polymorphisms at positions -988, -800, -509, codon 10 and codon 25 on TGF-beta gene in 138 SLE patients and 182 healthy controls were analyzed in this study. TGF-beta polymorphisms were determined by PCR amplification and sequencing. With the previous polymorphic data of interleukin-4 (IL-4) -590 and interleukin-10 (IL-10) -819, associations of cytokine genotyoe and allele frequencies were analyzed. Results showed that there were differences in the genotype distribution of TGF-beta promoter region at position -509 and in the signal sequence at codon 10 (Leu¡÷Pro) between case and control groups in this study. However, no significant differences were found for all the TGF-beta polymorphisms. Allele frequency of IL-10 -819 was significantly associated with the susceptibility of SLE (p = 0.011). No significant associations were found between lupus nephritis with all the cytokine polymorphisms, but CNS involvement and lung involvement were associated with the polymorphisms studied in this research.

名古屋大学博士学位論文 学位の種類 : 博士(医学)(論文) 学位授与年月日:平成5年9月14日 水谷大裕氏の博士論文として提出された

published_or_final_version / Paediatrics and Adolescent Medicine / Master / Master of Research in Medicine

published_or_final_version / abstract / Paediatrics and Adolescent Medicine / Master / Master of Philosophy

published_or_final_version / abstract / toc / Paediatrics and Adolescent Medicine / Master / Master of Philosophy

No description available.

Introduction: Systemic lupus erythematosus (SLE) is a disabling, chronic, multisystem autoimmune disease that occurs in women of childbearing years (15-40) and spans a lifetime. Little is known about the relevance that social support has in the context of mental health wellbeing for patients with SLE. Physicians may be an adequate source of support when it comes to SLE. Since there are arrays of triggers for depression, there is a need to understand the SLE experience to help with disease management. Objective: To examine the association of social support from a physician and the mental health wellbeing of SLE patients. Methods: We examined 652 SLE patients from the Georgians Organized Against Lupus (GOAL) cohort. Descriptive analysis was performed. Univariate analysis was performed to examine the associations of the main dependent variables (Short Form Health Survey (SF-12) and Patient Health Questionnaire (PHQ-9)) and each independent variable. Both, univariate and multivariate logistic regression analyses were conducted to determine associations between selected characteristics and main independent variables (emotional or social support and social support from a physician) with the categorized mental component score and PHQ9 depression score, individually and together. Ninety-five percent confidence intervals were used to determine statistical significance. Results: SLE patients who perceived having enough emotional/social support were found to have an overall better mental health status than the average American, and 64% less likely to be depressed compared to patients who did not have enough emotional/social support. Patients who were categorized as having social support from a physician were found to be in poorer mental health statuses, as measured by the MCS SF-12 and PHQ9 depression score. Conclusion: The findings of this study show that emotional or social support is associated with a better mental health well-being for SLE patients. SLE patients who have enough emotional or social support were found to have above normal general mental health and less depression. This study did not show any direct associations between physician social support and mental health wellbeing.

Systemic Lupus Erythematosus (SLE), a prototypic multi-organ autoimmune disease, is associated with a dramatically increased risk of coronary artery disease (CAD) manifesting as angina, myocardial infarction and sudden cardiac death. Traditional cardiac risk factors such as hypertension and hypercholesterolemia, measured at baseline in accordance with the Framingham model, only partially account for the increased risk of CAD in SLE. In this thesis, I have shown that blood pressure (BP), lipids and novel risk factors such as the inflammatory marker high-sensitivity C-reactive protein (hsCRP), take a dynamic course in SLE, with more than half of the variance in serial measurements over time occurring within rather than between individuals. This variability is due to changes in disease activity, treatment, accrual of other cardiac risk factors, and complications such as infection. I have demonstrated that by capturing cumulative exposure over time, ‘summary measures’ such as arithmetic mean and time-adjusted mean (AM) are better able to quantify CAD risk in patients with SLE than single-point-in-time measurements of risk factors. By incorporating ‘summary measures’ such as mean and AM into time-dependent covariate survival analysis models, I was able to quantify the magnitude of increase in CAD risk associated with increments in systolic and diastolic BP, and to demonstrate and quantify the association between several lipids / lipoproteins and CAD risk in SLE. Using this methodology, I was also able to demonstrate that despite marked variability over time, ‘summary measures’ of hsCRP are independently predictive of CAD risk among patients with SLE, highlighting the pivotal role of inflammation in atherosclerosis. Furthermore, I was able to determine lipid and hsCRP ‘cut-points’ that will aid clinicians in identifying a subgroup of patients with SLE who are at significantly increased cardiac risk.

Systemic Lupus Erythematosus (SLE), a prototypic multi-organ autoimmune disease, is associated with a dramatically increased risk of coronary artery disease (CAD) manifesting as angina, myocardial infarction and sudden cardiac death. Traditional cardiac risk factors such as hypertension and hypercholesterolemia, measured at baseline in accordance with the Framingham model, only partially account for the increased risk of CAD in SLE. In this thesis, I have shown that blood pressure (BP), lipids and novel risk factors such as the inflammatory marker high-sensitivity C-reactive protein (hsCRP), take a dynamic course in SLE, with more than half of the variance in serial measurements over time occurring within rather than between individuals. This variability is due to changes in disease activity, treatment, accrual of other cardiac risk factors, and complications such as infection. I have demonstrated that by capturing cumulative exposure over time, ‘summary measures’ such as arithmetic mean and time-adjusted mean (AM) are better able to quantify CAD risk in patients with SLE than single-point-in-time measurements of risk factors. By incorporating ‘summary measures’ such as mean and AM into time-dependent covariate survival analysis models, I was able to quantify the magnitude of increase in CAD risk associated with increments in systolic and diastolic BP, and to demonstrate and quantify the association between several lipids / lipoproteins and CAD risk in SLE. Using this methodology, I was also able to demonstrate that despite marked variability over time, ‘summary measures’ of hsCRP are independently predictive of CAD risk among patients with SLE, highlighting the pivotal role of inflammation in atherosclerosis. Furthermore, I was able to determine lipid and hsCRP ‘cut-points’ that will aid clinicians in identifying a subgroup of patients with SLE who are at significantly increased cardiac risk.

Systemic lupus erythematosus (SLE) is a relatively rare autoimmune disease with no known aetiology or cure. In addition to numerous physical symptoms, those living with SLE have also been shown to experience significant emotional and psychosocial difficulties. There has been little psychological research into SLE despite the rapidly increasing interest in health psychology and quality of life issues over the last two decades. One such issue that has commanded particular attention is that of cognitive bias in individuals with chronic pain and/or chronic illness. Cognitive bias toward illness-related information is theorised to indicate the presence of an illness self-schema, and is a valuable tool of investigation as it permits access to a level of cognitive structure that is inaccessible via self-report instruments. The primary focus of the present study is to investigate recall bias for pain- and illness-related words in SLE patients. This bias is explored relative to the recall of neutral words and depression-related words, and also relative to the responses of rheumatoid arthritis (RA) patients and healthy controls. Two hypotheses are proposed: firstly, that bias is related to disease activity; and secondly, that bias is related to the combination of illness and depression. The findings provide support for the second hypothesis, with the additional caveat that the nature of the pain/illness stimuli used is important in determining the presence of cognitive bias. No recall bias for illness-related words as a whole was found in any of the groups, nor was there evidence of a recall bias in the SLE and RA patients when they were divided according to depression status. However, when the illness words were examined separately according to �sensory pain� and �disability-related� words, a clear bias for disability words was found in the depressed patient group. It is concluded that there is a relationship between depression in chronically ill individuals, and the way in which such individuals process disability-related words. In accordance with the schema-enmeshment model (Pincus & Morley, 2001), it is suggested that both a pain-schema and an illness-schema exist, and it is when these two schemas become enmeshed with the self-schema that depression occurs in chronic pain/chronically ill patients. The cognitive bias assessment paradigm adopted in this study-one that is typically used in similar investigations-is lengthy, requires sophisticated equipment and can be difficult to interpret on an individual level. The present study investigates the relationship between cognitive biases in SLE patients and a recently-developed task, PRISM, which appears to symbolise the enmeshment of illness-, pain- and self-schemas. Analyses confirmed that recall of negative illness words was the only independent predictor of PRISM scores. This suggests that PRISM, a quick and easy task to administer, may have considerable usefulness as a clinical tool to assess information relevant to the enmeshment of illness- and self-schema. A greater understanding of schema and the processing styles of chronically ill patients will allow for more effective psychological treatment such that quality of life can be improved.