Search

Objectives: This study aimed to investigate disparities in clinical profiles and autoantibody patterns between patients with and without neuropsychiatric systemic lupus erythematosus (NPSLE) in a cohort and to identify risk factors associated with NPSLE in the Chinese population. Methods: SLE patients were retrospectively reviewed from two tertiary hospitals. The relationships between NPSLE and immunological biomarkers were explored. Results: Among the 945 SLE patients, 75 (7.94%) were diagnosed with NPSLE. The most prevalent NP manifestations involved cognitive disorder (30.67%), headache (26.67%), seizure disorder (26.67%), and psychosis (26.67%).We observed significant associations between psychosis and anti-β2GPI antibodies (F = 6.092, p = 0.015), polyneuropathy and anti-Scl70 antibodies (F = 20.161, p < 0.001), demyelinating syndrome and anti-cardiolipin antibodies (F = 6.637, p = 0.011), myasthenia gravis and anti-RNP (F = 5.864, p = 0.017), and anti-Smith antibodies (F = 5.096, p = 0.026). Multivariate logistics analysis showed that anti-prothrombin (aPT) IgM antibodies (OR = 10.985, CI 1.279–94.343, p = 0.029), age (OR = 1.169, CI 1.032–1.325, p = 0.014), and serum creatinine (SCr) (OR = 1.014, CI 1.003–1.025, p = 0.009) were independent risk factors of NPSLE, while anti-Sjogren syndrome antigen B (SSB) antibodies (OR 0.023, CI 0.002–0.622, p = 0.023) and high complement C3 (OR = 0.001, CI 0–0.045, p < 0.001) indicated reduced risk of NPSLE. Conclusion: Various neuropsychiatric manifestations in SLE were found to be correlated with specific autoantibodies. Independent risk factors for NPSLE included aPT IgM antibodies, age, and elevated serum creatinine, while the absence of anti-SSB antibodies and low complement C3 levels were associated with increased risk. Key points: •Significant associations were found between specific autoantibodies and neuropsychiatric symptoms, shedding light on potential biomarkers for predicting and understanding NPSLE. •The study identifies independent risk factors for NPSLE in the Chinese population, including the presence of anti-prothrombin IgM antibodies, older age, elevated serum creatinine, and lower complement C3 levels. [ABSTRACT FROM AUTHOR]

Objective: To identify disease‐specific serum chemokine profiles and potential anti‐inflammatory chemokines in three rheumatic diseases. Methods: The discovery cohort included 18 patients with rheumatoid arthritis (RA), 20 patients with primary Sjögren's syndrome (pSS), 24 patients with systemic lupus erythematosus (SLE) and 28 healthy subjects. Findings from the discovery cohort were validated in two replication cohorts, consisting of 23 patients with SLE matched with 23 healthy subjects and 62 patients with SLE, 16 patients with ANCA‐associated vasculitis (AAV), and 32 healthy controls, respectively. Serum levels of chemokines were determined using multiplex assay or ELISA. Results: In the discovery cohort, serum levels of multiple chemokines were increased in one or more diseases in comparison to healthy subjects, including CCL2, CCL20, CXCL9, CXCL10, and CXCL11 in SLE, CCL2, CCL4, and CXCL11 in pSS, and CCL2, CCL4, and CXCL9 in RA. Notably, serum levels of CCL3 (p =.0003) and CXCL5 (p =.0003) were decreased in SLE. The SLE‐specific decrease in CXCL5 serum levels was confirmed in the two replication cohorts, with p =.0034 and p =.0006, respectively. Moreover, a positive correlation between serum levels of CXCL5 and circulating platelet counts (R =.71, p =.00018) in SLE observed in the discovery cohort was confirmed in both replication cohorts (R =.52, p =.011 and R =.49, p =.00005, respectively). Conclusion: In the present study, we demonstrate that serum levels of CXCL5 are decreased in patients with SLE and positively correlated with circulating platelet count. These findings suggest that platelet‐associated CXCL5 is presumably involved in the development of SLE. [ABSTRACT FROM AUTHOR]

Objective: Systemic lupus erythematosus (SLE) is a prototypical autoimmune disease with differences in prevalence and severity among ancestral groups. This study was undertaken to identify novel genetic components, either shared by or distinct between Asian and European populations. Methods: Both trans‐ancestral and ancestry‐specific meta‐analyses of genome‐wide association studies (GWAS) for SLE were performed, involving 30,604 participants of European, Chinese, or Thai origin. Using public epigenomic data and expression quantitative trait loci, fine‐mapping analyses were conducted to identify putative causal variants and genes for the newly identified loci. Performance of polygenic risk scores for the Thai cohort was evaluated by comparing different training data. Results: A 1‐bp deletion upstream of IFNLR1 was found to be associated with SLE, with the risk allele correlated with increased expression of IFNLR1. This gene encodes interferon‐λ (IFNλ) receptor 1, providing evidence of a role of type III IFN signaling in SLE. An intronic variant in SLC29A3 was found to be associated with SLE in Asians only. The putative risk variant may modulate SLC29A3 expression in a monocyte‐specific manner. SLC29A3 encodes a lysosomal nucleoside transporter, and subsequent analyses suggested that reduced lysosomal function and phagocytosis might be the mechanism underlying this association. Ancestry‐shared loci in or near TAOK3, CHD9, CAMK1D, ATXN1, and TARBP1 and Asian‐specific loci close to PEX2, FCHSD2, and TMEM116 also reached the genome‐wide significant association with SLE. In addition, trans‐ancestral meta‐analysis was shown to be valuable in risk prediction for individuals without ancestry‐matched data. Conclusion: In this study both shared and Asian‐specific loci for SLE were identified, and functional annotation provided evidence of the involvement of increased type III IFN signaling and reduced lysosomal function in SLE. [ABSTRACT FROM AUTHOR]

Objectives To identify novel genetic loci associated with systemic lupus erythematosus (SLE) and to evaluate potential genetic differences between ethnic Chinese and European populations in SLE susceptibility. Methods A new genome-wide association study (GWAS) was conducted from Jining, North China, on 1506 individuals (512 SLE cases and 994 matched healthy controls). The association results were meta-analysed with existing data on Chinese populations from Hong Kong, Guangzhou and Central China, as well as GWAS results from four cohorts of European ancestry. A total of 26 774 individuals (9310 SLE cases and 17 464 controls) were included in this study. Results Meta-analysis on four Chinese cohorts identifies KLF2 as a novel locus associated with SLE [rs2362475; odds ratio (OR) = 0.85, P =2.00E-09]. KLF2 is likely an Asian-specific locus as no evidence of association was detected in the four European cohorts (OR = 0.98, P  =0.58), with evidence of heterogeneity (P =0.0019) between the two ancestral groups. Meta-analyses of results from both Chinese and Europeans identify STAB2 (rs10082873; OR= 0.89, P =4.08E-08) and DOT1L (rs4807205; OR= 1.12, P =8.17E-09) as trans-ancestral association loci, surpassing the genome-wide significance. Conclusions We identified three loci associated with SLE, with KLF2 a likely Chinese-specific locus, highlighting the importance of studying diverse populations in SLE genetics. We hypothesize that DOT1L and KLF2 are plausible SLE treatment targets, with inhibitors of DOT1L and inducers of KLF2 already available clinically. [ABSTRACT FROM AUTHOR]

Systemic lupus erythematosus (SLE), a worldwide autoimmune disease with high heritability, shows differences in prevalence, severity and age of onset among different ancestral groups. Previous genetic studies have focused more on European populations, which appear to be the least affected. Consequently, the genetic variations that underlie the commonalities, differences and treatment options in SLE among ancestral groups have not been well elucidated. To address this, we undertake a genome-wide association study, increasing the sample size of Chinese populations to the level of existing European studies. Thirty-eight novel SLE-associated loci and incomplete sharing of genetic architecture are identified. In addition to the human leukocyte antigen (HLA) region, nine disease loci show clear ancestral differences and implicate antibody production as a potential mechanism for differences in disease manifestation. Polygenic risk scores perform significantly better when trained on ancestry-matched data sets. These analyses help to reveal the genetic basis for disparities in SLE among ancestral groups. The presentation of systemic lupus erythematosus has been known to differ by ancestry, but the underlying genetic factors remain unclear. Here, the authors report ancestry-specific susceptibility loci and better risk prediction when using data from matched ancestral groups. [ABSTRACT FROM AUTHOR]

Systemic lupus erythematosus (SLE) is a genetically complex autoimmune disease. Despite the significant progress made in identifying susceptibility genes for SLE, the genetic architecture of the disease is far from being understood. In this study, we set to replicate a number of suggestive association signals found in genome-wide association studies (GWASs) in additional independent cohorts. Replication studies were performed on Han Chinese cohorts from Hong Kong and Anhui, involving a total of 2,269 cases and 5,073 controls. We identified a missense variant in IRF3 (rs7251) reaching genome-wide significance through a joint analysis of GWAS and replication data (OR = 0.876, P = 4.40E-08). A significant correlation was observed between rs7251 and lupus nephritis (LN) by subphenotype stratification (OR = 0.785, P = 0.0128). IRF3 is a key molecule in type I interferon production upon nucleic acid antigen stimulations and may inhibit regulatory T cell differentiation. Further elucidation of the mechanism of this association could help us better understand the pathogenesis of SLE. [ABSTRACT FROM AUTHOR]

Backgroud: This study is to explore the prevalence of different stages of bone loss and the potential risk factors in rheumatic patients.Method: A cross-sectional study recruits 1398 rheumatic patients and 302 healthy subjects. Demographic data, blood, and bone mineral density (BMD) tests are collected. Risk factors for bone loss in rheumatic patients are analyzed by logistic regression.Results: (1) Rheumatic patients are consisted of 40.0% rheumatoid arthritis (RA), 14.7% systemic lupus erythematosus (SLE), 14.2% osteoarthritis (OA), 9.2% ankylosing spondylosis (AS), 7.9% gout, 7.0% primary Sjogren syndrome (pSS), 3.8% systemic sclerosis (SSc), and 3.2% mixed connective tissue disease (MCTD). (2) In male patients aged under 50 and premenopausal female patients, the bone mineral density score of AS (53.9%, P < 0.001) and SLE (39.6%, P = 0.034) patients is lower than the healthy controls (18.2%). (3) Osteopenia and osteoporosis are more prevailing in male patients aged or older than 50 and postmenopausal female patients with RA (P < 0.001), OA (P = 0.02) and SLE (P = 0.011) than healthy counterparts. (4) Those with SLE, RA and AS gain the highest odd ratio of 'score below the expected range for age', osteopenia and osteoporosis, respectively. (5) Age, female, low BMI and hypovitaminosis D are found negatively associated with bone loss. Dyslipidemia and hyperuricemia could be protective factors.Conclusion: Young patients with AS and SLE have a significant higher occurrence of bone loss, and older patients with RA, OA and SLE had higher prevalence than healthy counterparts. SLE, RA, SSc and AS were founded significant higher risks to develop into bone loss after adjustment. Age, BMI and gender were commonly-associated with bone loss in all age-stratified rheumatic patients. These findings were not markedly different from those of previous studies. [ABSTRACT FROM AUTHOR]

Objective To investigate the potential risk factors of the incidence of osteoporosis in patients with systemic lupus erythematosus （SLE）. Methods In this study, 125 sex- and age-matched SLE patients （SLE group） and 125 healthy controls （HC group） were screened from the Third Affiliated Hospital of Sun Yat-sen University,Fujian Provincial General Hospital, Ganzhou Municipal Hospital and the Second Affiliated Hospital of Shantou University Medical College using the PSM matching method. Clinical data were collected. Bone mineral density （BMD） of the lumbar spine, femoral neck and total hip was measured. T values in male and postmenopausal female aged≥50 years were calculated and Z values in male and premenopausal female aged < 50 years were calculated. The risk factors of the incidence of osteoporosis in SLE patients between two groups were identified by logistic regression analysis. Results The lumbar spine BMD （T value） in patients with SLE was lower than that in the HC group （P < 0.05）. The lumbar spine, femoral neck and total hip BMD （Z value） in the SLE group were lower than those in the HC group （all P < 0.05）. Besides, the probability of abnormal BMD regarding the T and Z values in the SLE group was higher compared with that in the HC group （both P < 0.05）. In the SLE group, the proportion of normal BMD according to the T value was lower than that in the HC group, especially the lumbar spine. In the SLE group, the proportion of lumbar spine, femoral neck and total hip BMD （Z value） lower than normal level was higher than that in the HC group. In the SLE group, long disease duration, history of glucocorticoid use, age > 50 years and coronary artery disease were the risk factors of osteoporosis in SLE patients. Conclusions SLE patients with long disease duration, history of glucocorticoid use, age > 50 years and coronary artery disease are high-risk population for osteoporosis.

This study not only provides a simple method for synthesis of a specific DNA-SeNPs, which is a simple and cost-saving nanosystem, for recognition and removal of anti-dsDNA autoantibodies both in serum from 128 clinically identified systemic lupus erythematosus (SLE) patients and kidney from 36 clinically identified lupus nephritis (LN) patients, but also sheds light on the possible action mechanisms of anti-dsDNA antibodies in the pathogenesis and progression of SLE. [Display omitted] • SLE-specific targeting DNA-SeNPs with perfect biocompatibility. • DNA-SeNPs highly efficient remove anti-dsDNA autoantibodies in serum of SLE patients. • DNA-SeNPs could visualize the distribution of anti-dsDNA antibodies in the LN. Systemic lupus erythematosus (SLE) with increasing morbidity and mortality rate is characterized by multisystem damage and diverse autoantibodies production, such as anti-double stranded (ds) DNA antibodies. It is noted that anti-dsDNA antibodies are essential in the pathogenesis and progression of SLE and lupus nephritis (LN), however; anti-dsDNA antibodies could not be specifically recognized and quickly removed in clinic. Therefore, it is urgently needed to develop SLE-specific targeting agents to improve the diagnose and treatment of SLE. Herein, a selenium nanosystem (DNA-SeNPs) with surface decoration of calf thymus DNA (ctDNA) was constructed to specifically recognize and remove anti-dsDNA autoantibodies in the serums of 128 SLE patients and in the kidneys of 36 LN patients. The nanotherapeutics exhibited perfect biocompatibility and safety in patients to directly eliminate anti-dsDNA antibodies. In addition, the clearance ratio of anti-dsDNA antibodies by DNA-SeNPs was notably higher than other products widely used in clinical practice, implying that the excellent removal efficiency of this nanotherapeutics. Importantly, DNA-SeNPs not only help to visualize the distribution of anti-dsDNA antibodies in the lesions of kidney, but also semi-quantify the deposition of these antibodies, which are the key cause of the local damage. To sum up, this study provides a simple approach for rational design of nanoscale SLE-targeting nanomedicine to improve the diagnose and treatment of SLE, also sheds light on the possible mechanisms of anti-dsDNA antibodies in the pathogenesis and progression of SLE. [ABSTRACT FROM AUTHOR]