Relationship between autoantibody clustering and clinical subsets in SLE: cluster and association analyses in Hong Kong Chinese

OBJECTIVE: This study aims to identify the existence of, and relationship between autoantibody clusters and clinical subsets in Chinese SLE patients. METHODS: Data from 1928 SLE patients from Hong Kong were analysed. Using cluster analysis, patients were grouped by autoantibodies into clusters. The frequencies of various clinical manifestations were then compared between each cluster. Separate association analyses between individual autoantibodies and clinical manifestations as well as between clinical manifestations were also performed without any prior clustering. RESULTS: Three separate autoantibody clusters were identified, each with significantly different clinical manifestations. Cluster 1 was characterized by anti-dsDNA and the greatest prevalence of renal disorder but the lowest frequencies of other clinical manifestations. Cluster 2 was represented by the predominance of anti-Smith, anti-RNP and aPL, with greater prevalence of malar rash, oral ulcers, arthritis and serositis. Cluster 3 was characterized by anti-Ro and anti-La with greater prevalence of discoid rash, photosensitivity and haematological involvement. Individual association analysis also revealed similar findings. Patients of clusters 2 and 3 were more closely related, while cluster 1 was more distinct, associated with renal disorder only and negatively associated or not associated with other manifestations. CONCLUSION: We conclude that autoantibody clustering and clinical subsets exist in SLE patients of our locality. These clusters may be viewed as a bipolar spectrum of related autoantibody and clinical manifestations. At one end are patients with over-representation of anti-dsDNA and renal disorder, while at the other end are two distinct autoantibody clusters (anti-Sm/anti-RNP/aPL and anti-Ro/anti-La) with overlapping of other clinical manifestations.postprin

Meta-analysis of two Chinese populations identifies an autoimmune disease risk allele in 22q11.21 as associated with systemic lupus erythematosus

INTRODUCTION: Systemic lupus erythematosus (SLE) is a heterogeneous disease with a diverse spectrum of clinical symptoms from skin rash to end-organ damage. 22q11.21 has been identified as a susceptibility region for several autoimmune diseases, including SLE. However, the detailed information for SLE association and the underlying functional mechanism(s) are still lacking. METHODS: Through meta-analysis of two genome-wide association studies (GWAS) on Chinese Han populations with a total of 1659 cases and 3398 controls matched geographically, we closely examined this region, especially on the reported single nucleotide polymorphisms (SNPs) associated with different autoimmune diseases and their relationships. We further replicated the most significant association SNP with SLE using 2612 cases and 2323 controls of Asian ancestry. RESULTS: All reported SNPs in this region with different autoimmune diseases were examined in the two GWAS data and meta- analysis result, and supportive evidence of association with SLE was found (meta-analysis P_meta ≤ 7.27E-05), which might require further investigation. SNP rs2298428 was identified as the most significant SNP associated with SLE in this region (P_meta = 2.70E-09). It showed independent effect through both stepwise and conditional logistic regression, and there is no evidence of other independent association signals for SLE in this region. The association of rs2298428 was further replicated in three cohorts from Hong Kong, Anhui and Thailand with a total of 2612 cases and 2323 controls (joint analysis of GWAS and replication result P_all = 1.31E-11, OR = 1.23). SNP rs2298428 was shown to be an eQTL for UBE2L3 gene in different cell types, with the risk allele (T) being correlated with higher expression of UBE2L3. This is consistent with earlier reports on higher expression of UBE2L3 in SLE cases. CONCLUSIONS: Association to distinct autoimmune diseases highlights the significance of this region in autoreactive responses and potentially shared functional mechanisms by these diseases.published_or_final_versio

Gene-Based Meta-Analysis of Genome-Wide Association Study Data Identifies Independent Single-Nucleotide Polymorphisms in ANXA6 as Being Associated With Systemic Lupus Erythematosus in Asian Populations

Objective Previous genome-wide association studies (GWAS), which were mainly based on single-variant analysis, have identified many systemic lupus erythematosus (SLE) susceptibility loci. However, the genetic architecture of this complex disease is far from being understood. The aim of this study was to investigate whether using a gene-based analysis may help to identify novel loci, by considering global evidence of association from a gene or a genomic region rather than focusing on evidence for individual variants. Methods Based on the results of a meta-analysis of 2 GWAS of SLE conducted in 2 Asian cohorts, we performed an in-depth gene-based analysis followed by replication in a total of 4,626 patients and 7,466 control subjects of Asian ancestry. Differential allelic expression was measured by pyrosequencing. Results More than one-half of the reported SLE susceptibility loci showed evidence of independent effects, and this finding is important for understanding the mechanisms of association and explaining disease heritability. ANXA6 was detected as a novel SLE susceptibility gene, with several single-nucleotide polymorphisms (SNPs) contributing independently to the association with disease. The risk allele of rs11960458 correlated significantly with increased expression of ANXA6 in peripheral blood mononuclear cells from heterozygous healthy control subjects. Several other associated SNPs may also regulate ANXA6 expression, according to data obtained from public databases. Higher expression of ANXA6 in patients with SLE was also reported previously. Conclusion Our study demonstrated the merit of using gene-based analysis to identify novel susceptibility loci, especially those with independent effects, and also demonstrated the widespread presence of loci with independent effects in SLE susceptibility genes. © 2015, American College of Rheumatology.postprin

A Green Route to Conjugated Polyelectrolyte Interlayers for High-Performance Solar Cells

Synthesis of fluorene‐based conjugated polyelectrolytes was achieved via Suzuki polycondensation in water and completely open to air. The polyelectrolytes were conveniently purified by dialysis and analysis of the materials showed properties expected for fluorene‐based conjugated polyelectrolytes. The materials were then employed in solar cell devices as an interlayer in conjunction with ZnO. The double interlayer led to enhanced power conversion efficiency of 10.75 % and 15.1 % for polymer and perovskite solar cells, respectively

Membranous lupus nephritis in Chinese children - a case series and review of the literature

We retrospectively reviewed the cases of 13 lupus nephritis children with pure membranous glomerulonephritis (MGN; Group A) and ten children with mixed proliferative and membranous nephritis (Group B). The children were identified through a territory-wide survey of patients between 1990 and 2003. All were ethnic Chinese. Age at diagnosis ranged from 3.7 to 18.6 years (Group A) and from 9.6 to 22.1 years (Group B). Female-to-male ratios were 12:1 (Group A) and 9:1 (Group B). Group A patients were more often nephrotic than Group B patients (11/13 vs. 5/10, p = 0.17). The glomerular filtration rate (GFR) at presentation was normal in all but two patients (one from each group). For induction, Group B patients consistently received prednisolone and cyclophosphamide; in contrast, the cytotoxic regimens in Group A patients varied from cyclophosphamide (five patients), mycophenolate mofetil (two patients), azathiorpine plus cyclosporine (one patient), and azathioprine alone (one patient). After a median follow-up of 7.6-7.8 years, one Group A patient had died of fulminant lupus. One survivor in Group B had a GFR < 90 ml/min per 1.73 m(2). Proteinuria persisted in five Group A patients and two Group B patients. In conclusion, Group B patients had good prognosis in terms of survival and proteinuria control. The only death occurred in Group A, and five of the 12 survivors in this group had persistent proteinuria. Further studies are needed to define the best treatment for pure lupus MGN

Evaluating different imaging strategies in children after first febrile urinary tract infection

We conducted a retrospective multicenter review to estimate the prevalence of urological abnormalities in Chinese children with first febrile urinary tract infection (UTI) and to evaluate the selective imaging strategy recommended by the NICE guideline for detecting underlying abnormalities. Atypical UTI was defined as in the NICE UTI guideline. Overall, 576 boys and 244 girls aged below 24 months were reviewed. All underwent ultrasound (US) and micturating cystourethrogram (MCUG) and 612 underwent DMSA scans. US was abnormal in 73 (8.9%) and vesicoureteral reflux was shown in 195 patients (23.8%). A total of 126 patients were considered to have remediable urological abnormalities requiring additional surgical or medical interventions. The NICE guideline yielded excellent negative predictive values (NPV) of 100-94.4% in girls but 91% in boys. If all boys underwent US and DMSA and only those with atypical UTI or abnormal US or DMSA proceeded to MCUG, then the NPV increased to 95.2% and 97.4% for boys aged below and above 6 months, respectively. These revised strategies would substantially save invasive studies-DMSA and MCUG in 27 and 74% of girls aged below and above 6 months, respectively, or MCUG in 23 and 59% of boys aged below and above 6 months, respectively.link_to_subscribed_fulltex