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A cohort of 306 patients was recruited. Questionnaire interview, review of medical records and clinical assessments were performed to obtain information regarding disease status, healthcare resources utilization and HRQoL. / Cost-of-illness studies measure the monetary burden that a disease imposes on society or individuals. The substantial financial burden of SLE has been demonstrated in a modest number of studies and a restricted number of countries. However, there is no study investigating the relationship between disease costs and NPSLE/flare. / In summary, this study has provided support for our hypotheses. The socioeconomic impact of SLE in Hong Kong is considerable. The presence of NPSLE and flare are significantly associated increase disease costs but not impaired HRQoL. These suggest that management, which can lead to early diagnosis and effectively control disease activity and prevent lupus flares, may reduce disease costs due to both healthcare consumption and loss of productivity. / Systemic lupus erythematosus (SLE) is a multi-factorial autoimmune disease that primarily affects young women, characterized by a chronic remitting-relapsing (flare) disease course. Central nervous system is one of the most common affect systems in SLE. Neuropsychiatrie SLE (NPSLE) is associated with impairment of quality of life, accumulated disease damage, disability and employment. Flare, an increase in disease activity over a defined period, is an important outcome in the assessment of SLE. Uncontrolled disease activity results in cumulative organ damage which is associated with increased mortality. / The main findings were as follows. 1. The average annual total costs were USD 13,307 (2006 US dollars) per patient. The direct costs dominated the total costs (62%), and the costs of inpatient care contributed 52% of the direct costs. Costs of SLE per subject are higher than those of other chronic diseases in Hong Kong. 2. Patients with NPSLE incurred significantly higher direct and indirect costs compared to those without NPSLE. The number of NPSLE event was an independent explanatory variable associated with both increased direct and indirect costs. 3. Annual direct costs and indirect costs were significantly higher in those with flares. The number of flare was an independent explanatory variable associated with increased direct costs. Patients with multi-organ flares or renal/neuropsychiatric flares incurred higher direct costs than those with single organ flare or those with minor organ flares. 4. Patients with SLE had significantly lower level of HRQoL compared with Hong Kong general population. The presence of NPSLE and flare only weakly associated with impairment of HRQoL. / The present thesis was a retrospective cost-of-illness study on Chinese patients in Hong Kong with SLE within working age, aiming to 1. estimate the direct and indirect costs of SLE from a societal perspective; 2. ascertain the relationship between NPSLE and direct and indirect costs; 3. ascertain the relationship between flare and direct and indirect costs; 4. investigate the relationship between HRQoL and NPSLE/flares. / We hypothesized that: I. SLE is associated with substantial socioeconomic burden as a result of NPSLE and flare; 2. patients with NPSLE or flares may experience more compromised health-related quality of life (HRQoL). / Zhu, Yaner. / Adviser: Edmund K. Li. / Source: Dissertation Abstracts International, Volume: 72-04, Section: B, page: . / Thesis (Ph.D.)--Chinese University of Hong Kong, 2010. / Includes bibliographical references (leaves 190-214). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. Ann Arbor, MI : ProQuest Information and Learning Company, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese.

Thesis (Ph. D.)--University of Virginia, 2001. / Includes bibliographical references (leaves 129-144). Also available online through Digital Dissertations.

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

SLE is a complicated autoimmune disease with a strong genetic basis. Owing to the successful application of genome-wide association study (GWAS) on complex traits, significant progresses have been made in identifying susceptible loci for SLE. So far, more than 30 loci have been shown to have robust association with the disease, significantly improving our understanding of this disease. On the other hand, these loci only confer relatively small increments in disease risk, leaving a large amount of disease heritability unexplained. Several limitations may lead to the issue of “missing heritability”, such as the insufficient statistical power of standard GWAS, the failure to explore independent signals with marginal effects, and other forms of genetic variations or interactions that can hardly be detected by the current GWAS approach. In the current study, efforts have been made on solving the issue of missing heritability. Firstly, in order to increase the statistical power of GWAS, we performed meta-analysis of two existing SLE GWASs on Chinese populations, and replicated the findings in additional samples from Hong Kong, Anhui, and Thailand. We identified ARID5B and CDKN1B as novel SLE susceptibility genes through this approach. Secondly, considering the limitation of previous GWASs that only focus on the most significant signal in an individual region, we revisited the established loci by in-depth analysis on the basis of meta-analysis and followed up the findings with large-scale replication efforts. We found three additional independent signals in 11q23.3 as being associated with SLE. Thirdly, given the importance of independent effects in predisposing disease susceptibility, we performed gene-based analysis to combine the marginal independent signals within a gene to identify novel susceptibility genes. Our results demonstrated the widespread existence of independent effects within known SLE susceptibility genes, and we also identified ANXA6 as a novel SLE susceptibility gene. Lastly, we also made some efforts in the characterization of the related genes, and we identified several regulatory SNPs (rSNPs) predisposing individuals to SLE via affecting expression of the corresponding genes. In addition, we also found that epistatic interaction of variants in a previously established susceptibility gene, ETS1,correlates with cytokine (e.g.IL-17) abnormality in SLE cases. The current work represents several practical approaches to improve the power of GWAS. The findings might enrich the list of SLE susceptibility genes as well as advance our knowledge on the etiology of this complicated disease. Importantly, the current study highlights the importance of independent effects and rSNPs in conferring disease susceptibility, which may shed light on further exploration on the genetic architecture of SLE. / published_or_final_version / Paediatrics and Adolescent Medicine / Doctoral / Doctor of Philosophy

Systemic Lupus Erythematosus (SLE) is an autoimmune disease which is characterized by high level of autoantibody detected in the body. This disease is female predominant with a male to female ratio 1: 9. SLE could cause damage to different organ systems and central nervous system is one of them. Patients diagnosed with SLE could suffer from psychiatric problems like cognitive dysfunction, depression and anxiety. Neurogenesis refers to the process by which new neurons are generated. Although it has been widely reported that neurogenesis could be enhanced under pathological conditions such as stroke, Huntington’s disease and epilepsy, study focusing on the relationship between neurogenesis and SLE remains limited. In the present study, by using NZB/W F1 mice as the animal model of SLE, we could demonstrate that there was dramatic increase of neuronal precursor cells at the corpus callosum after the onset of SLE symptoms. Meanwhile, as IBA-1 positive cells and GFAP positive cells also increased significantly there, this suggested inflammation has taken place. I hypothesized there were upregulation of immunological factors after the onset of SLE symptoms and those factors were responsible for the neurogenesis. In my in vitro study, cytokine- interferon gamma (IFN gamma) has been shown to promote neuronal progenitor cells (NPCs) to differentiate into neuronal linage but it did not obviously affect the cell proliferation and migration. For the other cytokine and chemokines, including interleukin-10 (IL-10), interleukin-8 (IL-8), macrophage-derived chemokine (MDC), stromal cell-derived factor 1 alpha (SDF-1alpha) and thymus and activation regulated chemokine (TARC), all of them had no effect on NPC proliferation and differentiation. As far as we know, this is the first study to report SLE could enhance neurogenesis. Concerning the role of inflammation and IFN gamma on the neurogenesis in our case, it should be worth for further investigation, which will benefit future development of novel treatment targeting psychiatric symptoms in SLE. / published_or_final_version / Anatomy / Master / Master of Philosophy

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the production of autoantibodies against self-antigens. SLE has a complex multifactorial genetic basis. Genome wide association studies (GWAS) have implicated polymorphisms causing decreased expression in many genes in SLE etiology and will likely continue to implicate new genes. Therefore, the aim of my project was to create a modular system where the effect of knocking down a gene of interest can be studied in cell culture in a timely manner. This was accomplished by inserting shRNAmirs targeting our validation gene, A20, into a retroviral vector, creating viral particles using a packaging cell line, and infecting cultured cells. Two shRNAmirs were determined to be effective by qRT-PCR and Western blots on infected cells. Vectors carrying these shRNAmirs were used to infect ex vivo B cells and BMDCs, and results suggested that A20 knockdown may mediate functional changes in both cell types.

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the production of autoantibodies against self-antigens. SLE has a complex multifactorial genetic basis. Genome wide association studies (GWAS) have implicated polymorphisms causing decreased expression in many genes in SLE etiology and will likely continue to implicate new genes. Therefore, the aim of my project was to create a modular system where the effect of knocking down a gene of interest can be studied in cell culture in a timely manner. This was accomplished by inserting shRNAmirs targeting our validation gene, A20, into a retroviral vector, creating viral particles using a packaging cell line, and infecting cultured cells. Two shRNAmirs were determined to be effective by qRT-PCR and Western blots on infected cells. Vectors carrying these shRNAmirs were used to infect ex vivo B cells and BMDCs, and results suggested that A20 knockdown may mediate functional changes in both cell types.

Thesis (Ph. D.)--University of Hong Kong, 2008. / Also available in print.

Thesis (Ph. D.)--University of Hong Kong, 2008. / Also available online.