METHODS: A retrospective study involving pregnant women with SLE who had antenatal follow-up and delivery in between 1 January 2007 and 1 January 2017. All participants were retrospectively enrolled and categorized into two groups based on hydroxychloroquine treatment during pregnancy.
RESULTS: There were 82 pregnancies included with 47 (57.3%) in the hydroxychloroquine group and 35 (42.7%) in the non-hydroxychloroquine group. Amongst hydroxychloroquine users, there were significantly more pregnancies with musculoskeletal involvement (p = 0.03), heavier mean neonatal birthweight (p = 0.02), and prolonged duration of pregnancy (p = 0.001). In non-hydroxychloroquine patients, there were significantly more recurrent miscarriages (p = 0.003), incidence of hypertension (p = 0.01) and gestational diabetes mellitus (p = 0.01) and concurrent medical illness (p = 0.005). Hydroxychloroquine use during pregnancy was protective against hypertension (p = 0.001), and the gestational age at delivery had significant effect on the neonatal birthweight (p = 0.001). However, duration of the disease had a significant negative effect on the neonatal birthweight (p = 0.016).
CONCLUSION: Hydroxychloroquine enhanced better neonatal outcomes and reduced adverse pregnancy outcomes and antenatal complications such as hypertension and diabetes.
METHODS: We performed an allelic association analysis in patients with SLE, followed by a meta-analysis assessing genome-wide association data across 11 independent cohorts (n = 28,872). In silico bioinformatics analysis and experimental validation in SLE-relevant cell lines were applied to determine the functional consequences of rs34330.
RESULTS: We replicated a genetic association between SLE and rs34330 (meta-analysis P = 5.29 × 10-22 , odds ratio 0.84 [95% confidence interval 0.81-0.87]). Follow-up bioinformatics and expression quantitative trait locus analysis suggested that rs34330 is located in active chromatin and potentially regulates several target genes. Using luciferase and chromatin immunoprecipitation-real-time quantitative polymerase chain reaction, we demonstrated substantial allele-specific promoter and enhancer activity, and allele-specific binding of 3 histone marks (H3K27ac, H3K4me3, and H3K4me1), RNA polymerase II (Pol II), CCCTC-binding factor, and a critical immune transcription factor (interferon regulatory factor 1 [IRF-1]). Chromosome conformation capture revealed long-range chromatin interactions between rs34330 and the promoters of neighboring genes APOLD1 and DDX47, and effects on CDKN1B and the other target genes were directly validated by clustered regularly interspaced short palindromic repeat (CRISPR)-based genome editing. Finally, CRISPR/dead CRISPR-associated protein 9-based epigenetic activation/silencing confirmed these results. Gene-edited cell lines also showed higher levels of proliferation and apoptosis.
CONCLUSION: Collectively, these findings suggest a mechanism whereby the rs34330 risk allele (C) influences the presence of histone marks, RNA Pol II, and IRF-1 transcription factor to regulate expression of several target genes linked to proliferation and apoptosis. This process could potentially underlie the association of rs34330 with SLE.
METHODS: This study enrolled 147 SLE patients from the Asia Pacific Lupus Collaboration (APLC) cohort, who had BMD and TBS assessed from January 2018 until December 2018. Twenty-eight patients sustaining VF and risk factors associated with increased fracture occurrence were evaluated. Independent risk factors and diagnostic accuracy of VF were analyzed by logistic regression and ROC curve, respectively.
RESULT: The prevalence of vertebral fracture among SLE patients was 19%. BMD, T-score, TBS, and TBS T-score were significantly lower in the vertebral fracture group. TBS exhibited higher positive predictive value and negative predictive value than L spine and left femur BMD for vertebral fractures. Moreover, TBS had a higher diagnostic accuracy than densitometric measurements (area under curve, 0.811 vs. 0.737 and 0.605).
CONCLUSION: Degraded microarchitecture by TBS was associated with prevalent vertebral fractures in SLE patients. Our result suggests that TBS can be a complementary tool for assessing vertebral fracture prevalence in this population.