A comparison of the performance of the Assessment of SpondyloArhritis international Society (ASAS) classification criteria, European Spondyloarthropathy Study Group (ESSG) classification criteria, and Modified New York (MNY) criteria in a cohort of Chinese spondyloarthritis patients

BACKGROUND: The existing Modified New York (MNY) criteria and European Spondyloarthropathy Study Group (ESSG) criteria are defective in early diagnosis of patients with spondyloarthritis. The objective of this study was to reclassify a Chinese cohort of patients with previous expert-diagnosed spondyloarthritis according to the recently issued Assessment of SpondyloArthritis international Society (ASAS) classification criteria for axial spondyloarthritis and the two existing criteria, the ESSG criteria and MNY criteria and to compare the clinical characteristics including disease duration, disease activity, and spinal mobility between patients fulfilling these criteria. METHODS: Consecutive patients diagnosed by expert opinion from a tertiary centre were classified into three groups: the Ankylosing Spondyloarthritis (AS) by MNY criteria; undifferentiated spondyloarthritis (USpA) by ESSG criteria (USpA/ESSG), and those by ASAS classification criteria only (USpA/ASAS). Functional status was studied by Bath Ankylosing Spondylitis Functional Index (BASFI). Disease activity was evaluated by Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and C-reactive protein. Spinal mobility including modified Schober test and chest expansion was determined. RESULTS: A total of 128 spondyloarthritis patients (92 male and 36 female) were recruited. USpA/ASAS group identified patients with shortest disease duration (9.2±2.3 years, 11.6±3.8, 18.7±2.2 years in USpA/ASAS group, USpA group, and AS group respectively; P<0.01). USpA/ASAS and USpA/ESSG groups were better than AS group in terms of BASFI, modified Schober test and chest expansion. C-reactive protein and BASDAI were similar in the three groups. CONCLUSION: The ASAS classification criteria are shown to identify spondyloarthritis patients at an earlier stage when spinal mobility and functional status are preserved. This group of USpA patients demonstrated comparable disease activity to other groups, suggesting a need and predictably better outcome for early treatment.published_or_final_versionThe 15th Medical Research Conference (15th MRC), Department of Medicine, University of Hong Kong, Hong Kong, 16 January 2010. In Hong Kong Medical Journal, 2010, v. 16 n. 1, suppl. 1, p. 18, abstract no. 2

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

Usefulness of Certain Protein Biomarkers for Prediction of Coronary Heart Disease

Identification of biomarkers can help monitor and prevent cardiovascular disease (CVD) risk. We performed an exploratory analysis to identify potential biomarkers for coronary heart disease (CHD) in participants from the Life Conditions, Stress, and Health study. A total of 1,007 participants (50% women), randomly selected from the general population, were followed for incident CHD at 8 and 13 years of follow-up. Plasma levels of 184 CVD-related biomarkers were measured in samples collected at baseline in 86 cases with CHD and 184 age- and sex-matched controls by proximity extension assay. Biomarker levels were presented as normalized protein expression values (log 2 scale). After adjusting for confounding factors, 6 biomarkers showed significant association with incident CHD at 13 years. In a sensitivity analysis, this association remained significant at 8 years for 3 biomarkers; collagen α-1(I) chain (COL1A1), bone morphogenetic protein-6 (BMP-6), and interleukin-6 receptor α chain (IL-6Rα). When entering these biomarkers in the full adjustment model simultaneously, their association with incident CHD at 13 years remained significant, hazards ratio being 0.671, 0.335, and 2.854, respectively per unit increase in normalized protein expression values. Subjects with low COL1A1, low BMP-6, and high IL-6Rα levels had a hazards ratio of 5.097 for incident CHD risk (p = 0.019), compared with those without. In conclusion, we identified COL1A1, BMP-6 and IL-6Rα as biomarkers for incident CHD over a long-term follow-up in this exploratory analysis. For COL1A1 and BMP-6 this has not been previously reported. Further studies are needed to confirm our findings and establish their clinical relevance

Acupuncture and related interventions for carpal tunnel syndrome: systematic review

© The Author(s) 2019. Objective: To synthesize evidence on the effectiveness of acupuncture and related therapies for primary carpal tunnel syndrome (CTS) by conducting a systematic review of randomized controlled trials (RCTs). Data Sources: Nine databases were searched for potential RCTs from their inception till July 2019. Review Methods: RCTs which reported at least one of the three outcomes were included: symptom severity, functional status and pain. Included RCTs were appraised using the Cochrane Risk of Bias Tool. Results: A total of 10 RCTs (728 participants) were included. Majority were at high risk of bias for blinding of participants, personnel and outcome assessors. When compared to conventional medications, manual acupuncture showed significant superior effect in reducing symptom than ibuprofen (mean difference (MD) on Symptom Severity Scale (SSS)) = –5.80, 95% confidence interval (CI): −7.95 to −3.65) and prednisolone (MD = −6.50, 95% CI: −10.1, −2.86). Electroacupuncture plus splinting was more effective in reducing symptom severity than splinting alone (SSS score: MD = −0.20, 95% CI: −0.36 to −0.03). Manual acupuncture showed significantly superior effect than ibuprofen in improving functional status (Functional Status Scale (FSS): MD = −1.84, 95% CI: −2.66 to −1.02). The combination of electroacupuncture and splinting showed more improvement in functional status compared to splinting alone (FSS: MD = −6.22, 95%CI: −10.7 to −1.71). Triple treatment of acupuncture, magnetic spectrum heat lamp and splinting showed stronger pain relief than splinting alone. Conclusion: For both symptom relief and function improvement, manual acupuncture is superior to ibuprofen while electroacupuncture plus splinting outperforms splinting alone. Limited evidence showed electroacupuncture’s potential role in pain reduction

Validation of a novel definition of low disease activity state in systemic lupus erythematosus

Plenary Session 5: Outcome measures and treatment targets in SLEBackground and aims While a 'Treat-to-target' principle is widely advocated in management of systemic lupus erythematosus (SLE), there is currently no internationally agreed definition of low disease activity in lupus. In 2015, the Asia-Pacific Lupus Collaboration presented a novel consensus definition of a safe state in lupus, the 'Lupus Low Disease Activity State' (LLDAS). (http://dx.doi.org/10.1136/annrheumdis-2015-207726) Methods This was a prospective study to determine whether LLDAS predicted lower flare-ups, damage and mortality. 339 SLE patients were recruited and followed for 30 months. Multivariable binomial regression was used to determine factors associated with LLDAS and Cox proportional hazard model to determine whether prior higher% of days in LLDAS would be associated with lower future flare-ups. Results Mean patient age was 48.1 years and mean disease duration 19.6 years. Female to male ratio=16 to 1. 79 flareups were documented. 92.6% of patients had ever achieved LLDAS during the study period and 62.1% of patient-days were in LLDAS. No major demographic or prior disease presentations were found to be associated with the attainment of LLDAS. Patients with prior higher percentage of days in LLDAS had lower hazard of lupus flare-ups (HR=0.420, p=0.015) after adjustment for gender and age. The numbers of patient damage and death were insufficient for analysis. Conclusions LLDAS is an independent construct achievable by most patients of different history or background. Our preliminary study shows LLDAS can predict the risk of future flareups though further studies are needed to determine whether it is associated less lupus-related damage and lower mortality

Epistatic Interaction between Genetic Variants in Susceptibility Gene ETS1 Correlates with IL-17 Levels in SLE Patients

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