Comparison of Contributors to Mortality Differences in SLE Patients with Different Initial Disease Activity: A Larger Multicenter Cohort Study.

To explore the etiology of risk factors and quantify the mortality differences in systemic lupus erythematosus (SLE) patients with different initial disease activity. The Jiangsu Lupus database was established by collecting medical records from first-hospitalized SLE patients during 1999-2009 from 26 centers in Jiangsu province, China, and their survival status every five years. The initial SLEDAI scores [high (>12) vs. low-moderate (≤12)] differences in mortality attributable to risk factors were quantified using population attributable fraction (PAF), relative attributable risk (RAR) and adjusted relative risk (ARR). Among 2446 SLE patients, 83 and 176 deaths were observed in the low-moderate and high activity groups, with mortality rates of 7.7 and 14.0 per 1000 person years, respectively. Anemia was the leading contributor to mortality, with PAFs of 40.4 and 37.5 in the low-moderate and high activity groups, respectively, and explained 23.2% of the mortality differences with an ARR of 1.66 between the two groups. Cardiopulmonary involvement caused the highest PAFs in the low-moderate (20.5%) and high activity (13.6%) groups, explaining 18.3% of the mortality differences. The combination of anemia and cardiopulmonary involvement had the highest RAR, causing 39.8% of the mortality differences (ARR = 1.52) between the two groups. In addition, hypoalbuminemia and a decrease in the creatinine clearance rate accounted for 20-30% of deaths and explained 10-20% of the mortality differences between the two groups, while antimalarial drug nonuse accounted for about 35% of deaths and explained 3.6% of the mortality differences. Anemia, cardiopulmonary involvement and hypoalbuminemia may cause substantial mortality differences across disease activity states, suggesting additional strategies beyond disease activity assessment to monitor SLE outcomes.

Development and Verify of Survival Analysis Models for Chinese Patients With Systemic Lupus Erythematosus.

Background: The aim of this study is to develop survival analysis models of hospitalized systemic lupus erythematosus (h-SLE) patients in Jiangsu province using data mining techniques to predict patient survival outcomes and survival status. Methods: In this study, based on 1999-2009 survival data of 2453 hospitalized SLE (h-SLE) patients in Jiangsu Province, we not only used the Cox proportional hazards model to analyze patients' survival factors, but also used neural network models to predict survival outcomes. We used semi-supervised learning to label the censored data and introduced cost-sensitivity to achieve data augmentation, addressing category imbalance and pseudo label credibility. In addition, the risk score model was developed by logistic regression. Results: The overall accuracy of the survival outcome prediction model exceeded 0.7, and the sensitivity was close to 0.8, and through the comparative analysis of multiple indicators, our model outperformed traditional classifiers. The developed survival risk assessment model based on logistic regression found that there was a clear threshold, i.e., a survival threshold indicating the survival risk of patients, and cardiopulmonary and neuropsychiatric involvement, abnormal blood urea nitrogen levels and alanine aminotransferase level had the greatest impact on patient survival time. In addition, the study developed a graphical user interface (GUI) integrating survival analysis models to assist physicians in diagnosis and treatment. Conclusions: The proposed survival analysis scheme identifies disease-related pathogenic and prognosis factors, and has the potential to improve the effectiveness of clinical interventions.

Correlation of CRP genotypes with serum CRP levels and the risk of rheumatoid arthritis in Chinese Han population.

OBJECTIVE: C-reactive protein (CRP) is an important index for evaluating the disease activity of rheumatoid arthritis (RA). CRP may play a direct role in bone destruction in RA. Studies have demonstrated that serum CRP levels had a close correlation with tissue inflammation scores in patients with RA. In addition, genetic factors play a crucial role in the development of RA. In this study, we aimed to investigate the relationship between the CRP gene variants (rs1205 polymorphism) and the risk of RA in Chinese Han population. METHODS: 502 RA patients and 581 controls were included in this study. The associations between CRP gene variants and CRP levels and RA risk were investigated. RESULTS: We found that TT/ TT + CT genotype was significantly related with an increased risk of RA (TT vs CC: OR, 1.56, 95%CI, 1.01-2.40, P = 0.045; TT + CT vs CC: OR, 1.30, 95%CI, 1.02-1.65, P = 0.032). In addition, T allele was shown to associate with an elevated risk of RA. After subgroup analysis, we found that rs1205 polymorphism was significantly related with an enhanced risk of RA among females, individuals lower than 60 years, and subjects with a BMI > 25 kg/m2. Furthermore, data showed that the CRP gene rs1205 polymorphism correlated with CRP and ESR levels. Furthermore, the TT genotype was significantly associated with a reduction of CRP levels compared with CT or CC genotype. CONCLUSIONS: To sum up, this study reveals that rs1205 polymorphism of the CRP gene is related with an increased risk of RA and CRP levels in Chinese Han population. Key Points • The CRP gene rs1205 polymorphism is related with a higher risk of RA. • The CRP gene rs1205 polymorphism correlates with CRP and ESR levels. • The TT genotype of rs1205 polymorphism is linked with a reduction of CRP levels.

Predictors of improvement in disease activity in first hospitalized patients with systemic lupus erythematosus: a multicenter retrospective study of a Chinese cohort.

OBJECTIVES: To analyze the relative factors of improvement in disease activity (IDA) after first hospitalized treatment based on the systemic lupus erythematosus disease activity index (SLEDAI). METHODS: A total of 1069 adult systemic lupus erythematosus (SLE) patients who were hospitalized for the first time in 26 hospitals in Jiangsu Province from 1999 to 2009 were retrospectively analyzed. SLEDAI decrease ≥ 4 during hospitalization was identified as IDA. Relative factors of IDA were assessed by univariate and multivariate logistic regression. RESULTS: A total of 783 (73.2%) adult SLE patients showed IDA after the first hospitalization, while the remaining patients (n = 286) were in the non-IDA group. The IDA group had higher SLEDAI at admission; fewer patients had SLICC/ACR damage index (SDI) ≥ 1, comorbidities at admission, especially Sjögren's syndrome, abnormal serum creatinine, and glomerular filtration rate. More patients had mucocutaneous and musculoskeletal involvements, leukopenia, increased C-reactive protein, anti-dsDNA antibody positive, and hypocomplementemia at admission and were treated with methotrexate and leflunomide during hospitalization. After multivariate logistic regression analysis, SDI ≥ 1 (P = 0.005) and combined with Sjögren's syndrome (P < 0.001) at admission had negative association with IDA. Musculoskeletal involvement (P < 0.001), anti-dsDNA antibody positive (P = 0.012), hypocomplementemia (P = 0.001), and use of leflunomide (P = 0.030) were significantly related with IDA. CONCLUSION: Organ damage or comorbidities at admission were adverse to SLE improvement. Anti-dsDNA antibody positive, hypocomplementemia, musculoskeletal involvements, and leflunomide treatment had positive association with IDA of SLE. Key Points • Organ damage or comorbidities at admission were negatively correlated with SLE improvement. • Anti-dsDNA antibody positivity, hypocomplementemia, musculoskeletal involvements, and leflunomide treatment were positively associated with SLE improvement.

Clinical and laboratorial outcome of different age-onset systemic lupus erythematosus patients in Jiangsu, China: a multicentre retrospective study.

Studies on clinical features of systemic lupus erythematosus among different age-onset patients are lacking in China. This multicentre study aimed to systemically compare clinical manifestations, comorbidities, organ involvement, and laboratory findings among 797 Chinese juvenile-onset, adult-onset, and late-onset SLE (JSLE, ASLE, and LSLE) patients. They were classified into JSLE, ASLE, and LSLE groups if first diagnosed at < 18, 18-50, and > 50 years old, respectively. Chi-square test and analysis of variance were employed for categorical and continuous variables respectively. In younger-onset patients, the SLE Disease Activity Index 2000 score was significantly higher (JSLE vs. ASLE vs. LSLE = 17.43 ± 9.139 vs. 16.34 ± 8.163 vs. 14.08 ± 6.474, p = 0.031). Mucocutaneous symptoms (79.5% vs. 73.4% vs. 62.0%, p = 0.042), especially malar rash (76.1% vs. 66.1% vs. 53.5%, p = 0.011) occurred more frequently, and proteinuria rate was higher (54.5% vs. 56.3% vs. 36.6%, p = 0.007). In later-onset patients, cardiopulmonary involvement increased (11.4% vs. 24.3% vs. 29.6%, p = 0.012). In ASLE, hypoalbuminemia rate elevated (46.6% vs. 59.9% vs. 47.9%, p = 0.015). Our study demonstrated in a Chinese population that JSLE may be more active and suffer mucocutaneous disorders, while LSLE tended to suffer cardiopulmonary involvement at-onset. These findings may help identify treatment priorities when facing different age-onset SLE patients.

Low dosage use of cyclophosphamide improves the survival of patients with systemic lupus erythematosus.

OBJECTIVE: To investigate the effect of cyclophosphamide (CYC) on organ involvement and SLE patients' overall and cause-specific mortality. METHODS: Information about CYC prescription was taken from the Jiangsu Lupus database, which was set up to collect medical records from SLE patients since their first admission during 1999-2009 in Jiangsu province, China. Follow-up studies were carried out in 2010 and 2015 to check the survival status of the patients. Cox regression models were used to estimate the hazard ratio (HR) and 95% CI. Kaplan-Meier model was used to assess the effect of CYC on mortality between organ involvement and non-involvement. RESULTS: There were 221 deaths observed out of 2446 SLE patients. CYC users decreased overall mortality of SLE (8.4%) with adjusted HR (95% CI) of 0.74 (0.56-0.97), as compared to non-users. A decrease in overall mortality of SLE was found in the low dosage (< 600 mg) of CYC users, with adjusted HR (95% CI) of 0.54 (0.36-0.81). The protection of CYC on mortality of SLE was further observed in subgroups, such as female; SLEDAI score ≥ 15 group; and those with neuropsychiatric, renal, and hematological involvements, and low serum C3. In addition, CYC could eliminate the differences in mortality between organ involvement and non-involvement, including renal, neuropsychiatric, cardiopulmonary, gastrointestinal, and hematological involvement, but not for mucocutaneous and musculoskeletal involvement. CONCLUSION: Low dosage use of CYC decreased the risk of overall mortality of SLE. CYC might improve the survival of SLE patients with renal, neuropsychiatric, cardiopulmonary, gastrointestinal, and hematological involvements. Key Points • Cyclophosphamide decreases overall mortality of SLE patients. • Decreased mortality is mainly observed from low dosage use of cyclophosphamide. • Cyclophosphamide improves the survival of SLE patients when major systems such as renal, neuropsychiatric, cardiopulmonary, gastrointestinal, and hematological are involved.

Association Between the Interferon-γ +874 T/A Polymorphism and the Risk and Clinical Manifestations of Systemic Lupus Erythematosus: A Preliminary Study.

BACKGROUND: Interferon-gamma (IFN-γ) is a pivotal cytokine involved in the development of systemic lupus erythematosus (SLE). The IFN-γ +874 T/A polymorphism has been shown to be related to the susceptibility to SLE in other races, but this has not been investigated in the Chinese Han population. METHODS: We designed this study to interpret the potential correlation between this polymorphism and SLE risk in a Chinese Han population. We included 374 SLE patients and 405 controls in this study. Odds ratios and relevant 95% confidence intervals were figured out to evaluate the potential strength of the association. RESULTS: Data revealed that the IFN-γ +874 T/A polymorphism showed an association with an enhanced risk of SLE in this Chinese Han population. TA or TA +AA genotype carriers showed an increased risk of developing SLE. Subgroup analyses found that this polymorphism elevated the risk of SLE among females. Additionally, this polymorphism was associated with clinical manifestations of SLE including lupus nephritis, proteinuria, anti-dsDNA antibodies, anti-Sm antibodies, and SLICC/ACR damage index. Furthermore, we conducted a meta-analysis and found that this polymorphism was associated with the risk of SLE, especially among Asians. CONCLUSION: Totally, this study detects that the IFN-γ +874 T/A polymorphism is related to the risk and clinical manifestations of SLE in a Chinese Han population.

The relationship of polluted air and drinking water sources with the prevalence of systemic lupus erythematosus: a provincial population-based study.

Environmental exposures interact with genetic factors has been thought to influence susceptibility of systemic lupus erythematosus (SLE) development. To evaluate the effects of environmental exposures on SLE, we conducted a population-based cohort study across Jiangsu Province, China, to examine the associations between the living environment including air and water pollution, population density, economic income level, etc. and the prevalence and mortality of hospitalized SLE (h-SLE) patients. A total of 2231 h-SLE patients were retrieved from a longitudinal SLE database collected by the Jiangsu Lupus Collaborative Group from 1999 to 2009. The results showed that: It existed regional differences on the prevalence of h-SLE patients in 96 administrative districts; The distribution of NO2 air concentration monitored by atmospheric remote sensors showed that three of the ultra-high-prevalence districts were located in the concentrated chemical industry emission area; h-SLE patient prevalence was positively correlated with the excessive levels of nitrogen in drinking water; The positive ratio of pericarditis and proteinuria was positively correlated with the prevalence of h-SLE patients and pollution not only induced a high h-SLE patient prevalence but also a higher mortality rate, which might be attributed to NOx pollution in the air and drinking water. In summary, our data suggested that NOx in air and drinking water may be one of the important predispositions of SLE, especially for patients with renal involvement.

Wogonoside attenuates the articular cartilage injury and the infiltration of Th1/Th2-type cytokines in papain-induced osteoarthritis in rat model via inhibiting the NF-κB and ERK1/2 activation.

OBJECTS: Osteoarthritis is the most common joint disease and a major cause of functional limitation and pain in adults. This study aims to investigate the effect of wogonoside (WOG) on the progression of knee osteoarthritis (KOA) in model rats. MATERIALS AND METHODS: Rats KOA models were established and treated with different doses of WOG (10 mg/kg, 20 mg/kg and 30 mg/kg). The degree of cartilage injury was detected by Mankin scores via HE/Alcian blue staining. The levels of IFN-γ and IL-4 in peripheral blood and synovial fluid and the Th1/Th2 ratio were detected by flow cytometry. The model mice were injected with NF-κB p65 or ERK1/2 inhibitors or activators to further investigate the effect of WOG on KOA. RESULTS: WOG significantly improved cartilage tissue damage and reduced the Mankins score. WOG down-regulated the level of IFN-γ while up-regulated the expression of IL-4, which maintained the balance of Th1/Th2 cells. Further studies showed that the expression of NF-κB p65, phosphorylated p65, cytoplasmic ERK1/2 and nuclear ERK1/2 were all inhibited by WOG. The results of reverse verification experiments showed that the activator of NF-κB p65 and ERK1/2 weakened the protective effect of WOG on KOA, and the inhibitor of NF-κB p65ERK1/2 enhanced the protective effect of WOG on KOA. CONCLUSIONS: WOG inhibited the activation of NF-κB and ERK1/2 to alleviate the articular cartilage injury and Th1/th2 cytokine infiltration in KOA rats.

Angiotensin-(1-7) attenuates collagen-induced arthritis via inhibiting oxidative stress in rats.

The present study was designed to investigate the anti-rheumatic effects and the mechanism of angiotensin (Ang)-(1-7) in rat models with collagen-induced arthritis (CIA). The CIA model was established using male Wistar rats by intradermal injection of bovine collagen-II in complete Freund's adjuvant at the base of the tail. The levels of angiotensin converting enzyme 2 (ACE2)/Ang-(1-7)/Mas receptor (MasR) were reduced in CIA rats. The attenuation of paw swelling and arthritis scores and improvement of indexes of spleen and thymus were done by Ang-(1-7) injection in CIA rats. The increased levels of inflammatory cytokines, such as interleukin (IL)-1ß, IL-6, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ in the serum and hind paw were blocked by Ang-(1-7) administration. In addition, enhanced NADPH oxidase (Nox) activity, increased levels of superoxide anions and malondialdehyde (MDA), and weakened superoxide dismutase (SOD) activity, were all reversed by treatment with Ang-(1-7). Nox1 overexpression reversed the suppressing effects of Ang-(1-7) on paw swelling and arthritis scores in CIA rats. The Ang-(1-7)-induced improvement in spleen and thymus indexes in CIA rats was abolished by Nox1 overexpression. Nox1 overexpression reversed the inhibitory effects of Ang-(1-7) by increasing IL-1ß, IL-6, TNF-α, and IFN-γ levels in the serum and hind paw of CIA rats. These results demonstrated that Nox1 increased the oxidative stress in arthritis, and Ang-(1-7) improved rheumatism in arthritis via inhibiting oxidative stress.

Creatinine clearance rate predicts prognosis of patients with systemic lupus erythematosus: a large retrospective cohort study.

OBJECTIVE: To explore the association between the creatinine clearance rate (Ccr) and the prognosis of patients, and compared with estimated glomerular filtration rate (eGFR). METHODS: We retrospectively collected information of patients with SLE who were first hospitalized between 1999 and 2009 in Jiangsu Province, China, and followed up in 2010 and 2015. Ccr was calculated and dichotomized into normal group (Ccr ≥ 70) and decreasing group (Ccr < 70). The clinical characteristics of the two groups were compared and Cox proportional-hazards regression models were used to calculate hazard ratio (HR) and 95% confidence interval (CI). RESULTS: Among 1990 SLE patients, we observed 437 (22.0%) with decreased Ccr, including 237 cases (11.9%) with mild renal dysfunction, 136 cases (6.8%) with moderate renal dysfunction, and 64 cases (3.2%) with severe renal dysfunction. Compared to normal Ccr, decreasing Ccr had a higher risk for mortality with adjusted HR (95% CI) of 2.21 (1.59-3.06). Dose-response relationships were significantly found between increased mortality of SLE and decreased Ccr (p for trend < 0. 001), as well as eGFR. Positive associations were consistently observed in subgroups, such as systemic lupus disease activity index (SLEDAI) ≥ 15, without comorbidities and abnormal laboratory indexes. Decreasing Ccr was positively associated with mortality from infection and renal failure with HR (95% CI) of 1.80 (1.02-3.19) and 6.84 (3.05-15.36). CONCLUSIONS: A significant association has been observed between decreased Ccr and increased risk for mortality of SLE patients. Early clinical interventions to modulate the Ccr of SLE patients may be beneficial to their survival. Key points • Decreasing creatinine clearance rate (Ccr) was positively associated with an overall mortality of SLE patients, with a dose-response relationship. • Moreover, decreasing Ccr was associated with elevated mortality primarily due to infection and renal failure.

Association of antimalarial drugs with decreased overall and cause specific mortality in systemic lupus erythematosus.

OBJECTIVE: To evaluate the association and dose-response pattern between antimalarial drugs and overall and cause specific mortality in SLE patients. METHODS: Medical records including information on HCQ/chloroquine (CQ) prescription were extracted from Jiangsu Lupus database. The database was designed to collect data from SLE patients that first-hospitalized during 1999-2009 in Jiangsu province, China, and a follow-up for survival status was performed in 2010 and 2015. Cox and restricted cubic spline models were used to estimate the hazard ratio and 95% CI. RESULTS: We identified 221 deaths among 2446 SLE patients in total. Compared with non-users, decreased overall mortality was associated with either HCQ or CQ users, with adjusted hazard ratio (95% CI) of 0.49 (0.35, 0.67) and 0.49 (0.27, 0.87), respectively. The association between HCQ/CQ and overall mortality was similar across subgroups, such as patients with comorbidities and organ involvements. Interestingly, both the time and the daily dosage of HCQ/CQ use were related to decreased mortality of SLE in a linear dose-response relationship. In cause specific analyses, HCQ/CQ was inversely associated with death from renal insufficiency and other organ (cardiopulmonary, gastrointestinal and haematological) involvements, with adjusted hazard ratio (95% CI) of 0.23 (0.09, 0.55) and 0.25 (0.10, 0.62), respectively, yet it was not significantly associated with mortality from infection and neuropsychiatric involvements. CONCLUSION: Antimalarial drugs were associated with lower risk of SLE mortality, especially renal insufficiency- and other organ involvement-related death. The protective effects for survival might be augmented by adherence and full dosage of these drugs.

An Autoimmunogenic and Proinflammatory Profile Defined by the Gut Microbiota of Patients With Untreated Systemic Lupus Erythematosus.

OBJECTIVE: Changes in gut microbiota have been linked to systemic lupus erythematosus (SLE), but knowledge is limited. Our study aimed to provide an in-depth understanding of the contribution of gut microbiota to the immunopathogenesis of SLE. METHODS: Fecal metagenomes from 117 patients with untreated SLE and 52 SLE patients posttreatment were aligned with 115 matched healthy controls and analyzed by whole-genome profiling. For comparison, we assessed the fecal metagenome of MRL/lpr mice. The oral microbiota origin of the gut species that existed in SLE patients was documented by single-nucleotide polymorphism-based strain-level analyses. Functional validation assays were performed to demonstrate the molecular mimicry of newly found microbial peptides. RESULTS: Gut microbiota from individuals with SLE displayed significant differences in microbial composition and function compared to healthy controls. Certain species, including the Clostridium species ATCC BAA-442 as well as Atopobium rimae, Shuttleworthia satelles, Actinomyces massiliensis, Bacteroides fragilis, and Clostridium leptum, were enriched in SLE gut microbiota and reduced after treatment. Enhanced lipopolysaccharide biosynthesis aligned with reduced branched chain amino acid biosynthesis was observed in the gut of SLE patients. The findings in mice were consistent with our findings in human subjects. Interestingly, some species with an oral microbiota origin were enriched in the gut of SLE patients. Functional validation assays demonstrated the proinflammatory capacities of some microbial peptides derived from SLE-enriched species. CONCLUSION: This study provides detailed information on the microbiota of untreated patients with SLE, including their functional signatures, similarities with murine counterparts, oral origin, and the definition of autoantigen-mimicking peptides. Our data demonstrate that microbiome-altering approaches may offer valuable adjuvant therapies in SLE.

Interleukin-25 is upregulated in patients with systemic lupus erythematosus and ameliorates murine lupus by inhibiting inflammatory cytokine production.

Interleukin-25 (IL-25), an anti-inflammatory member of the IL-17 family of cytokines, has been extensively investigated in multiple autoimmune and inflammatory diseases. However, its pathogenic role in systemic lupus erythematosus (SLE) remains largely unknown. This study aimed to explore the expression and clinical significance of IL-25 in patients with SLE as well as its pathogenic role in lupus-prone MRL/lpr mice. The results showed that IL-25 mRNA and serum levels were increased in patients with SLE compared with those in healthy controls. Higher IL-25 mRNA and serum levels were found in patients with an active disease. IL-25 levels were positively associated with SLEDAI, anti-dsDNA, and IgG but negatively associated with C3 and C4. Ex vivo assay showed that IL-25 could inhibit the production of the inflammatory cytokines IL-1ß, IL-17, IL-6, and IFN-γ as well as TNF-α in the peripheral blood mononuclear cells in patients with SLE. In vivo studies revealed that treatment with IL-25 significantly ameliorated lupus symptoms in lupus-prone MRL/lpr mice by suppressing the production of inflammatory cytokines, including IL-1α, IL-1ß, IL-6, IL-12p70, IL-17A, and IFN-ß. Cumulatively, our results suggest that IL-25 levels are increased in patients with SLE and associated with disease activity; IL-25 plays a potent immunosuppressive role in the pathogenesis of SLE by suppressing the production of inflammatory cytokines. IL-25 could potentially be used as a diagnostic and therapeutic target for SLE treatment.

Associations between anti-melanoma differentiation-associated gene 5 antibody and demographics, clinical characteristics and laboratory results of patients with dermatomyositis: A systematic meta-analysis.

Anti-melanoma differentiation-associated gene 5 (MDA5) antibody is a specific biomarker in patients with dermatomyositis (DM). Results from several studies that examined the relationship between anti-MDA5 antibody and the demographics, clinical characteristics and laboratory results of DM patients have been conflicting. The purpose of this study was to identify the relationship, if any, of anti-MDA5 antibody with demographics, clinical characteristics and laboratory results of DM patients. PubMed, Web of Science, Embase and the Cochrane Library databases were searched for studies without language restrictions conducted before 16 March 2017. Stata version 12.0 software was used to calculate pooled odds ratios or weighted mean differences and corresponding 95% confidence intervals to determine the relationship between anti-MDA5 antibody and patient characteristics. Twenty studies comprising 1500 cases were included in this meta-analysis. Anti-MDA5 antibody was strongly associated with clinically amyopathic DM (CADM) and rapidly progressive interstitial lung disease (RPILD). Anti-MDA5 antibody also increased the risk of developing eight characteristics comprising Gottron's sign or papules, mechanic's hand, V rash, skin ulcers, panniculitis, alopecia, arthritis/arthralgia and pneumomediastinum, but reduced the risk of muscle weakness, classic DM (CDM) and elevated creatine kinase (CK). Our meta-analysis indicated that anti-MDA5 antibody is related to muscle weakness, Gottron's sign or papules, mechanic's hand, V rash, skin ulcers, panniculitis, alopecia, arthritis/arthralgia, pneumomediastinum, RPILD, CDM, CADM and elevated CK in patients with DM.

Prognosis for Hospitalized Patients with Systemic Lupus Erythematosus in China: 5-Year Update of the Jiangsu Cohort.

OBJECTIVE: To identify early signs associated with poor prognosis in Chinese patients with systemic lupus erythematosus (SLE) through a large population-based follow-up study. METHODS: Medical records of > 2,500 SLE patients that first hospitalized between 1999-2009 were collected from 26 centers across Jiangsu province, China, and entered into a database. These patients were followed-up for 5 to 15 years, and those remained contact and had known survival status in 2015 were assessed for the association of factors presented at the initial hospitalization with mortality at two time points (≤1year and > 1year). The independency of mortality factors was evaluated using multivariate Cox regression analysis. RESULTS: Among 1,372 patients we assessed, 92.3% were women and 17.2% were deceased in 2015. The main causes of death were infection (30.1%), neuropsychiatric impairment (14.8%), renal failure (14.4%) and cardiopulmonary involvement (8.5%). Hazard ratios (HR) of independent predictors for mortality (≤1year and > 1year, respectively) included hospital presentation of neuropsychiatric involvement (2.03 and 1.91), cardiopulmonary involvement (1.94 and 1.61) and increased serum creatinine (2.52 and 2.58). Patients older than 45 years and with disease durations more than 2 years at admission had unfavorable short-term outcome (HR 1.76 and 1.79), while the presence of anti-dsDNA and anti-Sm antibodies indicated diverse prognosis after 1 year (HR 1.60 and 0.45). Treatment with cyclophosphamide was beneficial for patient's first-year outcome (HR 0.50), and anti-malarial drugs significantly reduced the risk of mortality over different time points (HR 0.48 and 0.54). SLEDAI score, proteinuria or hypocomplementemia was not independently associated with the outcome in this cohort. CONCLUSION: SLE patients presented with vital organ damages rather than active disease at initial hospitalization are likely to have a poor outcome, especially for those with neuropsychiatric, cardiopulmonary involvements and renal insufficiency. Early and effective intervention with the use of anti-malarial drugs may decrease mortality.

Investigation on association between five common polymorphisms in vascular endothelial growth factor and prototypes of autoimmune diseases.

BACKGROUND: Vascular endothelial growth factor (VEGF) is a crucial regulator in angiogenesis. Previous research has indicated that modified VEGF-VEGFR signaling pathway has an impact on the development of inflammatory diseases. It has been proved that single nucleotide polymorphisms (SNPs) for critical genes might be associated with the susceptibility of autoimmune diseases. In this study, we targeted five common VEGF SNPs, i.e. -1154G>A, +405G>C, -2578C>A, +936C>T and -460T>C. Their associations with eleven prototypes autoimmune disease were assessed by our meta-analysis. METHODS: PubMed/Medline and CNKI were searched for related articles. Studies fulfilled the inclusion criteria were enrolled in this analysis. Meta-analysis was performed using odds ratio and 95% confidence intervals as effect measures. RESULTS: 73 studies from 30 relevant articles were retrieved in accordance with the data selection methods. A total of 11,354 cases and 8694 controls from the 30 included studies were enrolled in this meta-analysis. In the overall analysis, no statistically significant association was confirmed concerning five common VEGF polymorphisms and the susceptibility of autoimmune diseases. Interestingly, in the stratified analysis by ethnicity, the C allele of +405G>C polymorphism in Caucasian people was found to be correlated to increase autoimmune diseases risk, while an inverse trend of association was observed in Asian people. Also, decreased susceptibility to Graves' disease was detected in Caucasian people with G allele in +405G>C polymorphism. Besides, a trend of decreased risk of psoriatic arthritis was confirmed among population with T allele of +936C>T polymorphism. CONCLUSION: In summary, as suggested by our analysis, +405G>C polymorphism in VEGF might exert an influence on autoimmune diseases, with opposite effect observed in Asians and Caucasians. No association between the other four common SNPs (-2578C>A, -1154G>A and -460T>C) and autoimmune diseases susceptibility was confirmed.

[Clinical features and prognosis of patients with lupus nephritis].

OBJECTIVE: To explore the clinical features and prognosis of patients with lupus nephritis (LN) in a large multicenter lupus cohort of Jiangsu Province. METHODS: Medical records of 2 078 systemic lupus erythematosus (SLE) inpatients from 15 hospitals at the first admission from 1999 to 2012 were reviewed and classified into two groups with LN or without. The clinical features between two groups were compared with Mann-Whitney U or Chi-square test and potentially associated factors tested by Cox regression. RESULTS: A total of 883 (42.5%) hospitalized lupus patients were diagnosed as LN. And the median age at disease onset of LN patients was lower than that of those without LN [(30 ± 11) vs (32 ± 12) years, P < 0.01]. Cardiopulmonary involvement, neuropsychiatric disorder, gastrointestinal dysfunction, hematologic disease, ophthalmopathy, SLEDAI score > 9 at admission and SLE disease activity index (SLEDAI) score > 9 at discharge were more often seen in patients with LN compared to those without LN (31.5%, 7.9%, 13.9%, 69.0%, 1.5%, 77.4%, 29.8% vs 18.8%, 5.1%, 6.8%, 63.1%, 0.3%, 43.1%, 8.1%, all P < 0.01). The mortality rates at 1 or 5 years after first admission were both significantly higher in LN patients than those without LN (7.2%, 15.0% vs 3.1%, 6.3%, P < 0.01). Independent predictors for mortality in patients with LN were neuropsychiatric involvement[hazard ratio (HR) 2.46], SLEDAI score > 9 at discharge (HR 2.34), increased serum creatinine (HR 2.21) and elevated alanine aminotransferase and (or) aspartate transaminase (HR 2.09) whereas glucocorticosteroid therapy (HR 0.18) was a protective factor. CONCLUSION: LN is one common complication of SLE patients during an early stage. And LN patients are more prone to present other vital organ involvement, higher disease activity and worse treatment outcomes. When accompanied with neuropsychiatric involvement, increased serum creatinine or elevated transaminase, worse prognosis is expected. Glucocorticosteroid treatment may offer some benefits.

Prognostic indicators of hospitalized patients with systemic lupus erythematosus: a large retrospective multicenter study in China.

OBJECTIVE: To investigate the mortality of hospitalized patients with systemic lupus erythematosus (SLE) and determine the influential factors associated with poor prognosis. METHODS: Medical records of 1956 SLE inpatients from 15 hospitals during the period January 1, 1999, to December 31, 2009, were reviewed. All patients were followed up in January 2010. Potential factors associated with mortality were analyzed, comparing patients who were living with those who were deceased. The independency of those factors significantly related to death was determined by Cox regression analysis. RESULTS: Male to female ratio was 1:15 in this cohort; median age at disease onset was 30 years. Hematologic (70.0%), mucocutaneous (68.2%), musculoskeletal (57.9%), and renal (48.7%) involvements were most often seen in these patients at time of admission. The overall mortality was 8.5% (n = 166), with infection (25.9%), renal failure (19.3%), and neuropsychiatric lupus (18.7%) the leading 3 causes of death. Independent predictors for mortality in this cohort of SLE patients were neuropsychiatric involvement [hazard ratio (HR) 2.19], anemia (HR 1.69), SLEDAI score > 8 at discharge (HR 1.64), increased serum creatinine (HR 1.57), low serum albumin (HR 1.56), cardiopulmonary involvement (HR 1.55), and patient untreated before admission (HR 1.48), whereas the use of antimalarial drugs (HR 0.62) and positive anti-Sm antibody (HR 0.60) were shown to be protective factors. CONCLUSION: SLE patients with delayed treatment and refractory disease have poorer prognosis. A high incidence of death would be expected if they have neuropsychiatric involvement, anemia, azotemia, or cardiopulmonary involvement. Combination therapy with antimalarial drugs may provide some benefit to patients with SLE.