Includes bibliographical references / Background: Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease commonly affecting females of child-bearing age, hence hormonal changes in pregnancy are thought to play a role in disease activity - often necessitating changes in immunosuppression therapy. SLE is common in Cape Town, however, the effect of pregnancy on SLE and vice versa has not been well characterised. The aim of this study is to report on the pregnancy outcomes of patients with SLE presenting to the maternity department of Groote Schuur Hospital, Cape Town. Methods: This study was designed as a retrospective review of records of pregnant women known with SLE and followed up at the maternity section of Groote Schuur Hospital. The duration of the survey was from 1 January 2003 to 31 December 2013. Records were identified using the attendance registers in the relevant departments. Results: There were 61 pregnancies reviewed in 49 patients; 80.3% of the pregnancies were in patients of mixed ancestry and the rest (19.7%) in black African patients. The mean age at presentation of the current pregnancy was 27215.0 years. Mean gestational age at presentation and delivery was 13.0 ± 6.0 weeks and 28.9 ± 9.8 weeks respectively and 47.5% of the pregnancies were in patients with lupus nephritis (LN). Thirty-nine (63.9%) pregnancies reached the third trimester and 11.5% of all pregnancies ended in the first trimester. There was a lower number of live births to mothers of African ancestry than to those of mixed ancestry (p=0.001). In 55.7% of the pregnancies, no flare was reported while a renal flare was reported in 23%. Pregnancies in patients with LN had higher frequencies of flares (58.6% vs 31.3%; p=D.O32), pre-eclampsia (34.5% vs 12.5%; p=D.O41), longer stay in hospital (12.0 ± 9.1 days vs 6.1 ± 5.1 days; p=0.DO-4) and low birth weight babies (1.94 ± 1.02 kg vs 2.55 ± 0.95 kg; p=D.O46) than in patients without LN. Only 36 (59%) of the neonates were discharged home alive and of these 2 (5.6%) were to mothers of black African ancestry (p=0.001). Conclusion: Increased lupus activity in pregnant SLE patients may account for the increased deaths of neonates born to SLE mothers. Patients of black African descent and those with LN tend to have a poorer outcome. A multi-disciplinary approach to the management of SLE patients (of child-bearing age or pregnant) needs to be further evaluated.

published_or_final_version / Medicine / Master / Doctor of Medicine

Thesis (Ph. D.)--Ohio State University, 2004. / Title from first page of PDF file. Document formatted into pages; contains xviii, 212 p.; also includes graphics (some col.) Includes bibliographical references (p. 185-212). Available online via OhioLINK's ETD Center

Thesis (Ph. D.)--University of Hong Kong, 1998. / Includes bibliographical references (leaves 137-161).

No description available.

published_or_final_version / Pathology / Doctoral / Doctor of Philosophy

published_or_final_version / abstract / Medicine / Doctoral / Doctor of Philosophy

Systemic lupus erythematosus (SLE) is characterized as an autoimmune disorder with unclear etiology. To identify the genetic effect of SLE, a genome wide association study (GWAS) and its further replication were conducted on SLE patients in Asian populations and ethnically matched controls. Before this study, most of the confirmed association loci were identified by GWAS studies in European populations. Apart from the established associations, we identified a SLE susceptible single nucleotide polymorphisms (SNP) located in ETS1 (rs1128334, P=2.3E-11, OR=1.29) in four different cohorts. This locus is probably an Asian-specific susceptibility locus since no Caucasian study has reported further validation in the last years. A new susceptibility variant in UHRF1BP1 (rs13205210, P=4.4E-09, OR=1.49) independent from the previously confirmed SNPs in Caucasian study was also confirmed to be associated with SLE in the Hong Kong Chinese population. Meta-analysis was performed by introducing another Chinese Han GWAS data set from Anhui province, China. Three loci, TET3-DGUOK, CD80, DRAM1, were confirmed to be associated with SLE. Two loci with suggestive signals in Hong Kong GWAS and further replication were also confirmed by the meta-analysis: PTTG1-MiRNA146a, YDJC. In order to identify the genetic effect for females who have predominant chance to suffer from SLE, X chromosome specific meta-analysis based on the Hong Kong and Anhui GWAS data and further replication study were performed by considering the difference between females and males. A signal in PRPS2, and three independent signals in the Xq28 were confirmed with the replication in three different cohorts by considering both females and males. Gene-gene interactions were also investigated genome-widely in a hypothesis free manner based on the meta-analysis results. The further validation processes were preceeded based on each independent GWAS data set. Four pairswise interacting loci were found and cross validated by three methods including logistic regression and Multifactor Dimensionality Reduction (MDR) and information gain theory based on the Anhui GWAS data set. Further studies are still needed to better explain the real features of genetic epistasis and the potential biological roles. By incorporating two GWAS from the same population, the population difference is efficiently avoided. Together with the putative gene-gene interactions, this study presents a comprehensive analysis based on the GWAS data conducted on SLE. It may shed new light on the disease mechanisms of SLE. / published_or_final_version / Paediatrics and Adolescent Medicine / Doctoral / Doctor of Philosophy

abstract / Medicine / Doctoral / Doctor of Philosophy

No description available.