Acute effects of air pollution on lupus nephritis in patients with systemic lupus erythematosus: A multicenter panel study in China.

Air pollution may trigger systemic lupus erythematosus (SLE). However, few studies have investigated the associations between air pollution and complications of SLE, such as lupus nephritis (LN). In this study, multicenter longitudinal data from 13 hospitals in China, including 8552 SLE patients with 24,762 visits, were used. Based on the generalized estimating equation (GEE) model, we assessed the associations of LN occurrence with short-term exposures to different air pollutants including particulate matter with an aerodynamic diameter < 2.5 µm (PM2.5), sulfur dioxide (SO2), nitrogen dioxide (NO2), carbon monoxide (CO), and ozone (O3). We identified 2672 LN patients, and about half of them were from east China. Our results based on the entire data set showed that PM2.5 and NO2 were risk factors for LN within one month after exposure, with odds ratio of 1.16 (95% confidence interval (CI), 1.08-1.19) at lag 18 day and 1.19 (95% CI, 1.12-1.26) at lag 16 day relative to an interquartile range (IQR) increase in PM2.5 and NO2, respectively. This positive association between LN and NO2 was also observed for south, west, and east China. In addition, we found that the short term exposure to CO and O3 was not generally associated with LN. Finally, the negative associations of LN with SO2 were found for the entire region and east China. Our results implied that SLE patients may gain the health benefits of air quality improvement in China. Our work also provided evidence that short-term variations in air pollution may trigger LN, and further studies are needed to confirm these findings and the potential pathogenic mechanisms should be explored.

Association of variants in MMEL1 and CTLA4 with rheumatoid arthritis in the Han Chinese population.

BACKGROUND: The genome-wide association study era has made great progress in identifying susceptibility genes and genetic loci for rheumatoid arthritis (RA) in populations of White European ancestry. However, few studies have tried to dissect disease aetiopathogenesis in other ethnic populations. OBJECTIVE: To investigate these associations in the Han Chinese population. METHODS: Haplotypes from the HapMap database Chinese population were used to select tag-single-nucleotide polymorphisms (SNPs) (r(2)=0.8) across 19 distinct RA genomic regions. A two phase case-control association study was performed, with 169 SNPs genotyped in phase I (n=571 cases, n=880 controls), and 64 SNPs achieving p<0.2 in the first phase being genotyped in phase II (n=464 cases, n=822 controls). Association statistics were calculated using permutation tests both unadjusted and adjusted for the number of markers studied. RESULTS: Robust association was detected for MMEL1 and CTLA4, and modest association was identified for another six loci: PADI4, STAT4, PRDM1, CDK6, TRAF1-C5 and KIF5A-PIP4K2C. All three markers genotyped in MMEL1 demonstrated association, with peak signal for rs3890745 (p=2.6 × 10(-5) unadjusted, p=0.003 adjusted, OR=0.79). For CTLA4, significance was detected for three of five variants showing association, with peak association for marker rs12992492 (p=4.3 × 10(-5) unadjusted, p=0.0021 adjusted, OR=0.77). Lack of association of common variants in PTPN22 with RA in Han Chinese was confirmed. CONCLUSION: This study identifies MMEL1 and CTLA4 as RA susceptibility genes, provides suggestive evidence of association for a further six loci in the Han Chinese population and confirms lack of PTPN22 association in Asian populations. It also confirms the value of multiethnic population studies to help dissect disease aetiopathogenesis.

Association of STAT3 and TNFRSF1A with ankylosing spondylitis in Han Chinese.

OBJECTIVES: Recent association studies by the Australo-Anglo-American Spondyloarthritis Consortium (TASC) in Caucasian European populations from Australia, North America and the UK have identified a number of genes as being associated with ankylosing spondylitis (AS). A candidate gene study in a Han Chinese population was performed based on these findings to identify associated genes in this population. METHODS: A case-control study was performed in a Han Chinese population of patients with AS (n = 775) and controls (n = 1587) from Shanghai and Nanjing. All patients met the modified New York criteria for AS. The cases and controls were genotyped for 115 single nucleotide polymorphisms (SNPs) tagging IL23R, ERAP1, STAT3, JAK2, TNFRSF1A and TRADD, as well as other confirmation SNPs from the TASC study, using the Sequenom iPlex and the ABI OpenArray platforms. Statistical analysis of genotyped SNPs was performed using the Cochran-Armitage test for trend and meta-analysis was performed using METAL. SNPs in AS-associated genes in this study were then imputed using MaCH, and association with AS tested by logistic regression. RESULTS: SNPs in TNFRSF1A (rs4149577, p = 8.2 × 10⁻4), STAT3 (rs2293152, p = 0.0015; rs1053005, p = 0.017) and ERAP1 (rs27038, p = 0.0091; rs27037, p = 0.0092) were significantly associated with AS in Han Chinese. Association was also observed between AS and the intergenic region 2p15 (rs10865331, p = 0.023). The lack of association between AS and IL23R in Han Chinese was confirmed (all SNPs p > 0.1). CONCLUSIONS: The study results demonstrate for the first time that genetic polymorphisms in STAT3, TNFRSF1A and 2p15 are associated with AS in Han Chinese, suggesting common pathogenic mechanisms for the disease in Chinese and Caucasian European populations. Furthermore, previous findings demonstrating that ERAP1, but not IL23R, is associated with AS in Chinese patients were confirmed.

Kaempferol alleviates LD-mitochondrial damage by promoting autophagy: Implications in Parkinson's disease.

Emerging evidence indicates that unexpected lipid droplet (LD) deposition and peroxidation can accelerate organelle stress and plays a crucial role in the pathogenesis of neurodegenerative diseases (NDDs). In our previous study, we confirmed that kaempferol (Ka), a natural flavonoid small molecule, exhibited neuroprotective effects on mice with LPS-induced Parkinson's disease (PD). In addition, previous studies have shown that autophagy plays an important role in the regulation of cellular LD deposition. In the current study, we showed that Ka protected against TH+ neuronal loss and behavioral deficits in MPTP/p-induced PD mice, accompanied by reduced lipid oxidative stress in the substantia nigra pars compacta (SNpc). In cultured neuronal cells, Ka exhibited a relatively safe concentration range and significantly suppressed LD accumulation and cellular apoptosis induced by MPP+. Further study indicated that the protective effect of Ka was dependent on autophagy, specifically lipophagy. Critically, Ka promoted autophagy to mediate LD degradation in lysosomes, which then alleviated lipid deposition and peroxidation and the resulting mitochondrial damage, consequently reducing neuronal death. Furthermore, AAV-shAtg5-mediated Atg5 knockdown abolished the neuroprotective effects of Ka against lipid oxidation in PD mice. This work demonstrates that Ka prevents dopaminergic neuronal degeneration in PD via the inhibition of lipid peroxidation-mediated mitochondrial damage by promoting lipophagy and provides a potential novel therapeutic strategy for PD and related NDDs.

2018 Chinese Guidelines for the Diagnosis and Treatment of Rheumatoid Arthritis.

A multidisciplinary guideline development group was established to formulate this evidence-based diagnosis and treatment guidelines for rheumatoid arthritis (RA) in China. The grading of recommendations, assessment, development, and evaluation (GRADE) system was used to rate the quality of the evidence and the strength of recommendations, which were derived from research articles and guided by the analysis of the benefits and harms as well as patients' values and preferences. A total of 10 recommendations for the diagnosis and treatment of RA were developed. This new guideline covered the classification criteria, disease activity assessment and monitoring, and the role of disease modifying antirheumatic drugs (DMARDs), biologics, small molecule synthetic targeting drugs, and glucocorticoids in the treat-to-target approach of RA. This guideline is intended to serve as a tool for clinicians and patients to implement decision-making strategies and improve the practices of RA management in China.

Association of ERAP1, but not IL23R, with ankylosing spondylitis in a Han Chinese population.

OBJECTIVE: The results of a recent genome-wide association study have shown that ERAP1 and IL23R are associated with ankylosing spondylitis (AS) in Caucasian populations from North America and the UK. Based on these findings, we undertook the current study to investigate whether single-nucleotide polymorphisms (SNPs) covering the genes ERAP1 and IL23R are associated with AS in a Han Chinese population. METHODS: A case-control study was performed in Han Chinese patients with AS (n = 527) and controls (n = 945) from Shanghai and Nanjing. All patients met the modified New York criteria for AS. The Sequenom iPlex platform was used to genotype cases and controls for 21 tag SNPs covering IL23R and 38 tag SNPs covering ERAP1. Statistical analysis was performed using the Cochran-Armitage test for trend. RESULTS: Multiple SNPs in ERAP1 were significantly associated with AS (for rs27980, P = 0.0048; for rs7711564, P = 0.0081). However, no association was observed between IL23R and AS (for all SNPs, P > 0.1). The nonsynonymous SNP in IL23R, rs11209026, widely thought to be the primary AS-associated SNP in IL23R in Europeans, was found not to be polymorphic in Chinese. CONCLUSION: Our results demonstrate that genetic polymorphisms in ERAP1 are associated with AS in Han Chinese, suggesting a common pathogenic mechanism for the disease in Chinese and Caucasian populations, and that IL23R is not associated with AS in Chinese, indicating a difference in the mechanism of disease pathogenesis between Chinese and Caucasian populations. This may result from the fact that rs11209026, the nonsynonymous SNP in IL23R, is not polymorphic in Chinese patients, providing further evidence that rs11209026 is the key polymorphism associated with AS (and likely inflammatory bowel disease and psoriasis) in this gene.