The presence of autoantibodies in systemic lupus erythematosus (SLE) suggests a breach of tolerance. Recently, the IgM-IgD+ naïve B cell population has been shown to be enriched for self-reactive cells that are anergic in healthy subjects. Therefore, to determine whether there is altered selection of self-reactive cells in SLE, this population was examined using multiparameter flow cytometry. SLE patients had increased proportions of IgM-IgD+ cells in mature and transitional B cell compartments that were activated as compared to controls. Comparison of mature and transitional IgM-IgD+ B cell proportions suggested altered selection between the transitional to mature stages in SLE. There was no correlation between altered B cell function or genetic polymorphisms in B cell signalling molecules and the expansion or activation of IgM-IgD+ cells. Thus, selection of self-reactive B cells appears to be abnormal in SLE, but this does not appear to result from altered responses to Ig crosslinking.

The presence of autoantibodies in systemic lupus erythematosus (SLE) suggests a breach of tolerance. Recently, the IgM-IgD+ naïve B cell population has been shown to be enriched for self-reactive cells that are anergic in healthy subjects. Therefore, to determine whether there is altered selection of self-reactive cells in SLE, this population was examined using multiparameter flow cytometry. SLE patients had increased proportions of IgM-IgD+ cells in mature and transitional B cell compartments that were activated as compared to controls. Comparison of mature and transitional IgM-IgD+ B cell proportions suggested altered selection between the transitional to mature stages in SLE. There was no correlation between altered B cell function or genetic polymorphisms in B cell signalling molecules and the expansion or activation of IgM-IgD+ cells. Thus, selection of self-reactive B cells appears to be abnormal in SLE, but this does not appear to result from altered responses to Ig crosslinking.

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.