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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.

To explore the association between the creatinine clearance rate (Ccr) and the prognosis of patients, and compared with estimated glomerular filtration rate (eGFR). 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). 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). 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.

To investigate the effect of cyclophosphamide (CYC) on organ involvement and SLE patients' overall and cause-specific mortality.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.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.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.

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.

IntroductionA considerable proportion of patients with systemic lupus ery­thematosus (SLE) have liver enzyme abnormalities. We evaluated whether fibrosis-4 (FIB-4) was associated with increased mortality of SLE patients.Material and methodsA multicenter retrospective cohort study was conducted based on medical records of first-admission SLE patients who were hospitalized during 1999–2009 in Jiangsu province. FIB-4 was estimated by age, platelet (PLT) count, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and FIB-4. A Cox model and a restricted cubic spline (RCS) model were used to estimate hazard ratio (HR) and 95% confidence interval (95% CI).ResultsDuring up to 15 years of follow-up, 226 deaths were observed among 2331 SLE patients. Increased overall mortality was associated with abnormal groups of PLT, ALT, AST, and high FIB-4 (≥ 1.92), with adjusted HRs (95% CI) of 1.58 (1.19–2.11), 1.54 (1.14–2.07), 1.58 (1.17–2.12), and 1.88 (1.42–2.50), respectively. Moreover, significant dose-response relationships were found between mortality of SLE and those indexes, and it was nonlinear for PLT (p < 0.001), ALT (p = 0.046) and FIB-4 (p < 0.001), but not AST (p = 0.109). In cause-specific analyses, high FIB-4 index was directly associated with death from liver failure and indirectly associated with other death from infection and neuropsychiatric impairment. We found no significant differences of areas under curves (AUCs) between FIB-4 index and the disease activity index score of SLE.ConclusionsThis is the first report to describe the nonlinear association between FIB-4 index and increased mortality of SLE patients. The FIB-4 index may be used as an independent prognostic indicator for SLE patients.

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.

The objective of the study was to investigate the long-term treatment effects and predictive factors for treatment response and disease relapse for Takayasu's arteritis (TA). Eighty-one patients were recruited from the Department of Rheumatology, Zhongshan Hospital, Fudan University, between January 2009 and January 2015. The follow-up duration ranged from 6 to 36 months. Patients were divided into three groups: clinical remission (CR; n = 59); treatment-resistant (TR; n = 11); and disease relapse (DR; n = 11). Signs/symptoms, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and imaging items were recorded at baseline and at each visit. Kerr's criteria, physician's global assessment, and Indian Takayasu Clinical Activity Score (ITAS2010) were used to evaluate disease activity. Incipient disease was more common in CR patients compared with DR cases (69.49 vs. 36.36%, p = 0.05). Fewer patients aged 40 years were in the CR group in comparison with the DR group (57.63 vs. 90.91%, p = 0.04). In TR patients, high CRP levels (63.74 vs. 23.73%, p = 0.01) and aortic arch involvement (70.00 vs. 24.14%, p 0.01) were more common in comparison with CR cases. Patients with high CRP levels ( 25 mg/L) (OR = 1.61, p = 0.03) carried a higher risk for treatment resistance. Age 40 years (OR = - 2.82, p = 0.03), incipient disease (OR = - 2.47, p = 0.01), and treatment with cyclophosphamide (OR = - 2.07, p = 0.03) and hydroxychloroquine (OR = - 1.91, p = 0.05) could prevent disease relapse. Patients with high CRP levels carry a high risk of treatment resistance. In patients with incipient disease, aged 40 years, treatment with cyclophosphamide and hydroxychloroquine protects against disease relapse.

Iguratimod (IGU) is a novel disease-modifying anti-rheumatic drug (DMARD) in rheumatoid arthritis (RA). Like other DMARDs, IGU exhibited significant differences in effectiveness and safety. Aim: The aim of this study was to identify genetic predictorsof efficacyand toxicity of IGU in patients with RA. Materials & methods: Seven SNPs from IGU-metabolizing genes were genotyped in 272 IGU-treated patients with RA. Results: ABCG2 rs2231142 A allele conferred a higher response to IGU, while NAT2 rs1495742 G carriersconferred a lower response to IGU. CYP2C19*2 rs4244285 A carriers had higher risk for IGU-induced toxicity compared to the GG carriers. Conclusion: Our study suggests that the polymorphisms of ABCG2 (rs2231142), NAT2 (rs1495741)and CYP2C19*2 (rs4244285) may help to predict thetherapeutic effectiveness and toxicity of IGU in patients with RA.

The objective of this study was to systemically and comprehensively evaluate the associations between smoking and disease outcomes in patients with ankylosing spondylitis (AS). Information on smoking, clinical features, and sociodemographic characteristics was collected by a questionnaire administered directly to the patient. Group differences were analyzed by t test or chi-square test. Logistic regression analysis was conducted with the Bath AS Disease Activity Index (BASDAI), Bath AS Functional Index (BASFI), C-reactive protein, and erythrocyte sedimentation rate as the dependent variables and different stratification of smoking duration, smoking intensity, and cumulative smoking as independent variables. In order to compare our results with previous studies, meta-analysis was performed to calculate standardized mean difference (SMD) for relationship between outcomes and smoking status. A total of 1178 AS patients were analyzed. Compared with non-smokers, the risk of having active disease (BASDAI ≥ 4) was higher in patients who smoked at least 15 years, or 15 cigarettes per day, or 15 pack-years (OR = 1.70 [1.06, 2.73], 1.75 [1.08, 2.82], and 1.97 [1.06, 3.67], respectively); and smokers had increasing risk of BASDAI ≥ 4 with increasing years of smoking, or cigarettes per day, or pack-years (p-trend = 0.010, 0.008 and 0.006, respectively). The risk of having active disease was higher in patients who smoked at least 15 cigarettes per day or 15 pack-years (OR = 1.74 [1.06, 2.84] and 2.89 [1.56, 5.35], respectively), with increasing number of cigarettes per day and pack-years. Smokers had an increased risk of BASFI ≥ 4 (p-trend = 0.040 and 0.007, respectively). By meta-analysis, current, former and ever smokers had significantly higher BASDAI (SMD = 0.34 [0.18, 0.48], 0.10 [0.01, 0.19], and 0.27 [0.20, 0.34], respectively) and BASFI (SMD = 0.35 [0.16, 0.55], 0.30 [0.22, 0.39], and 0.35 [0.21, 0.50], respectively) compared to non-smokers. Smoking is a risk factor for greater disease activity and worse functioning in AS patients.

To assess the effectiveness of cyclophosphamide (CYC) versus methotrexate (MTX) for active Takayasu's arteritis (TA). The current study was based on a cohort of TA at Zhongshan Hospital, Fudan University. TA was diagnosed using the 1990 American College of Rheumatology criteria. Fifty-eight subjects receiving induction treatment with CYC (n = 46) or MTX (N = 12) were included in the analysis. Effectiveness and toxicity were assessed in all 58 cases. Clinical remission was defined as: Kerr score reduction to ≤ 1 and glucocorticoids (GC) treatment at a dose of ≤ 0.2 mg/kg/day (≤ 15 mg/day) at the end of the 6th month. At the baseline, the CYC group had higher Kerr scores (60.9% vs. 16.7% at ≥3, p = 0.044), higher ESR (55 ± 52 vs. 25 ± 22 mm/H, p = 0.048), ITAS_ESR (12.4 ± 1.7 vs. 9.1 ± 1.1 mg/L, p = 0.043). The 6-month clinical remission rate was 71.7% vs. 75% in the CYC and MTX group, respectively. In the CYC group, a significant decrease was observed in ESR (55 ± 52 vs. 25 ± 48 mm/H, p = 0.008), hs-CRP (27 ± 23 vs. 6.9 ± 6.6 mg/L, p = 0.007), ITAS (11.7 ± 2.2 vs. 7.0 ± 1.5, p = 0.048), and ITAS_ESR (7.1 ± 2.0 vs. 12.4 ± 1.7, p = 0.033). However, no significant reductions in these measures were demonstrated in the MTX group. Whole-body contrast enhanced magnetic resonance angiography (MRA) revealed significant radiologic improvement (wall enhancement scores: 4.2 ± 2.3 vs. 10.3 ± 3.8, p = 0.032) in the CYC group, but not in the MTX group. No severe adverse events occurred in any subject. Cyclophosphamide could be a better choice than methotrexate as induction treatment for patients with more severe Takayasu's arteritis.

The study aimed to determine whether unique clinical patterns of AS may exist in China, specifically to explore the different clinical manifestations caused by gender, HLA-B27 status, and age at disease onset. The multicenter cross-sectional survey was conducted and 1251 patients were enrolled across China, representing a broad spectrum of Chinese AS patients. The mean age at onset and diagnosis were 29.2 (11.4) and 33.5 (12.6) years, respectively. The male/female ratio was 2.7:1. Acute anterior uveitis (AAU) was experienced in 10.3% of AS patients and 9.1% patients had juvenile-onset AS (JoAS). Men were significantly younger at onset and diagnosis and showed a higher frequency of HLA-B27 positivity, JoAS, and AAU than women. HLA-B27-positive patients had a younger age of onset than HLA-B27-negative patients. HLA-B27-positive patients were nearly three times as likely to develop AAU than negative patients (P = 0.04). JoAS patients had a family history of AS more often than adult-onset AS (AoAS) patients, and 4.9% of JoAS patients underwent surgical treatments, a rate more than six times that of AoAS patients (P = 0.01). Men had higher levels of C-reactive protein than women, as did HLA-B27 positives compared to negative patients, and JoAS compared to AoAS (all P

Background B lymphocytes derived from patients with systemic lupus erythematosus (SLE) displayed abnormal activation and overexpression of auto-antibodies. It was reported that leptin was elevated in the sera of SLE patients and lupus mice, and blockade of leptin also remarkably improved the disease activity and renal pathology of lupus mice. Therefore, our study is to explore whether leptin in SLE regulates the activation and function of B cells. Objectives Our study is to explore whether leptin in SLE regulates the activation and function of B cells. Methods The sera and peripheral blood monocyte cells (PBMC) were isolated from healthy controls and SLE patients with Ficoll, then B cells were acquired through magnetic activated cell sorting (MACS). The sera were incubated in 56° for 30 min (complement inactivation). B cells were cultured in normal or SLE serum, with or without recombinant leptin. Anti-leptin antibody or inhibitions of the signalling pathways were added in SLE sera in order to observe the effects of B cells induced by leptin. Cell proliferation was detected by flow cytometry and carboxyfluorescein diacetate succinimdyl ester (CFSE), and the levels of auto-antibodies and inflammatory cytokines were examined by ELISA. The total and phosphorylated protein was tested with Western Blot analysis. Results Leptin R on B cells showed increased levels in SLE patients [(3.33±1.28)% v.s. (2.76±1.06)%, p Conclusions Leptin promote the activation and proliferation of B cells in SLE. Recombinant leptin or serum leptin from SLE patients both enhanced the expression of autoantibodies and inflammatory cytokines (IL-6, IL-10, TNF-a) of B lymphocytes. Additionaly, ERK1/2, and Jak/stat3,5 signalling pathways might play a vital role in this process. Disclosure of Interest None declared

We read with great interest the article by Muller-Calleja et al 1 in which a novel mechanism of hydroxychloroquine (HCQ) was discovered, which might explain well-established anti-inflammatory effects of antimalarials.2–4 HCQ and chloroquine (CQ), both known as antimalarial drugs, have become fundamental therapeutic elements in systemic lupus erythematosus (SLE) in these decades. However, their specific benefits on organ involvement and long-term outcome remain to be elucidated. To examine the role of antimalarials in different clinical aspects of Chinese patients with SLE, we retrieved the medical records of 1372 patients with SLE who experienced their first hospitalisation at 26 centres across Jiangsu, an eastern province of China, between January 1999 and December 2009 from a longitudinal SLE database collected by the Jiangsu Lupus Collaborative Group.5 Demographics of the enrolled patients are summarised in table 1. All the patients were followed up in 2015 to check for their survival status. Based on Kaplan-Meier survival analysis, the survival …

Background Nowadays the importance of antimalarials, especially hydroxychloroquine (HCQ) and chloroquine (CQ), in treatment of systemic lupus erythematosus (SLE) has been demonstrated. However, few have examined the efficacy of HCQ and CQ on eastern Chinese SLE patients. Methods The analysis is based on 1372 patients who were enrolled in a retrospective study of 26 centers from January 1st, 1999 through December 31st, 2009, during which time is their first hospitalization. Baseline and follow-up clinical, laboratory and therapeutic data and survival status before April 30th, 2015 were recorded. Statistical analysis consist of Chi-square test, t -test, Kaplan-Meier curves and logrank test. Results Compared with 562 patients without HCQ or CQ treatment, the hazard ratio (HR) of deaths in 810 patients taking those was reduced (HR 0.52, 95% CI 0.38–0.70, p 0.05). Other metabolic data, such as systolic and diastolic blood pressure, fasting blood sugar, Triglyceride and uric acid were similar between the two groups in two times of hospitalization. On second inpatient visit, disease activity (SLEDAI, blood sedimentation rate, complement) and organ involvements (SLICC) of those who took antimalarials and no users have no significant differences. Conclusions Use of HCQ or CQ lower the risk of mortality and TG levels of eastern Chinese SLE patients. Disclosure of Interest None declared

Background A rapid and sensitive time-resolved fluoroimmunoassay (TRFIA) based on the biotin–streptavidin amplification system was developed for the determination of anticyclic citrullinated peptide (anti-CCP). Methods Europium-labeled streptavidin derivatives combined with europium and anhydride of diethylene triamine pentaacetic acid were used to label streptavidin, biotin was coupled with rabbit anti-human IgG to form a biotin–anti-human IgG bridge between streptavidin–europium and the anti-CCP antibody in the immunoassay. The anti-CCP assay was carried out by measuring the fluorescence of Eu3+–streptavidin at 615 nm. Results The presented method produced a wide linear range from 0.58 to 9,463 U/ml, while it was only 591.4–18.48 U/ml when using an ELISA kit, and featured a detection limit up to 0.5 U/ml for anti-CCP. The values determined by the biotin–streptavidin–TRFIA and ELISA correlated well (R2 = 0.8927). The method was applied to determine anti-CCP in serum samples with satisfied recoveries of 96.45–104.63%. Conclusion The assay results obtained by the present method showed that biotin–streptavidin-amplified TRFIA improve the traditional ELISA kit for anti-CCP detection. Therefore, it offers a better alternative immunoassay in rheumatoid arthritis management.

Thalidomide is effective for treating severe cutaneous lupus patients. The aim of this study was to observe the optimum effective and maintenance doses of thalidomide to maximize clinical benefit and minimize side effects for patients with cutaneous lupus in China. Sixty-nine patients with lupus rash from eight hospitals in China were enrolled and treated with different doses of thalidomide. We started the dose of thalidomide at 25 mg daily and gradually increased administration dose once a week until erythema was markedly improved. The effective and maintenance doses were documented. The size of skin lesions was noted once a week. Systemic lupus erythematosus disease activity index (SLEDAI) score, levels of erythrocyte sedimentation rate (ESR), and serum TNF-α were measured before and after treatment. The remission rates were evaluated weekly until 8 weeks. Sixty-eight percent of patients showed an effective dose of 50 mg daily; another 13, 10, and 9 % of patients had an effective dose of 100, 75, and 25 mg daily, respectively. The maintenance dose was 50 mg daily for 71 % of the patients, and 100, 75, and 25 mg daily for 9, 14, and 6 % of the patients. SLEDAI score and serum ESR levels significantly decreased 4 weeks after thalidomide treatment. At the end of the fourth week, the rates of complete remission, partial remission, and no response were 56 % (n = 39), 41 % (n = 28), and 3 % (n = 2). At the eighth week, the rate of total remission rose up to 100 %. The most common side effects were drowsiness and constipation. No peripheral neuropathy was observed in these patients. Thalidomide at a dose of 50 mg daily may offer a better benefit to risk ratio in the treatment of Chinese cutaneous lupus patients.

Objective.Left atrial function plays a key role in maintaining an optimal cardiac output. Left ventricular diastolic dysfunction has been reported in systemic lupus erythematosus (SLE), but its effect on left atrial function has been largely overlooked. Our aim was to assess left atrial performance using real-time 3-D echocardiography (RT3DE) technology in patients with SLE.Methods.Our study included 102 patients with SLE without any cardiac symptoms, and 32 healthy controls. According to the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI), all subjects were classified into 3 groups: healthy controls, patients with an SDI = 0, and patients with an SDI ≥ 1.Results.Left atrial volume indexed to body surface area was dilated in subjects with SLE, whereas the left atrial passive emptying fraction (EF) was lower. Left atrial active EF was significantly higher in the SDI = 0 group than in controls (46.4 ± 9.1% vs 30.0 ± 10.3%, p < 0.05); however, it was significantly lower in the SDI ≥ 1 group than in the SDI = 0 group (41.2 ± 9.8% vs 46.4 ± 9.1%, p < 0.05). By multivariate linear analysis, the SDI was independently and positively associated with left atrial volume index and inversely associated with left atrial total function.Conclusion.Our study demonstrated that left atrial mechanical function and volume are impaired in SLE, particularly in patients with an SDI ≥ 1 and disease activity. RT3DE may have better diagnostic value than traditional echo indexes in detecting subclinical cardiac dysfunction in patients with SLE.

To explore the clinical features and prognosis of patients with lupus nephritis (LN) in a large multicenter lupus cohort of Jiangsu Province.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.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, P0.01]. Cardiopulmonary involvement, neuropsychiatric disorder, gastrointestinal dysfunction, hematologic disease, ophthalmopathy, SLEDAI score9 at admission and SLE disease activity index (SLEDAI) score9 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 P0.01). 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%, P0.01). Independent predictors for mortality in patients with LN were neuropsychiatric involvement[hazard ratio (HR) 2.46], SLEDAI score9 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.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.

In an effort to enhance the linear range of anti-CCP we developed a new immunoassay based on time-resolved fluoroimmunoassay. The precision, sensitivity, specificity, and stability of the assay were evaluated ELISA set as control. The anti-CCP IgG TRFIA kit we established had a wider detectable range than commercial ELISA ones. With regard to intra- and inter-assay precision, the TRFIA kit was better than threee commercial ELISA ones. The mean recovery rate was 101.0%. The TRFIA we developed for anti-CCP IgG detection yielded a more sensitive and reliable method for RA diagnosis and large-scale screening programs as well.

BACKGROUND: A rapid and sensitive time‐resolved fluoroimmunoassay (TRFIA) based on the biotin–streptavidin amplification system was developed for the determination of anticyclic citrullinated peptide (anti‐CCP). METHODS: Europium‐labeled streptavidin derivatives combined with europium and anhydride of diethylene triamine pentaacetic acid were used to label streptavidin, biotin was coupled with rabbit anti‐human IgG to form a biotin–anti‐human IgG bridge between streptavidin–europium and the anti‐CCP antibody in the immunoassay. The anti‐CCP assay was carried out by measuring the fluorescence of Eu(3+)–streptavidin at 615 nm. RESULTS: The presented method produced a wide linear range from 0.58 to 9,463 U/ml, while it was only 591.4–18.48 U/ml when using an ELISA kit, and featured a detection limit up to 0.5 U/ml for anti‐CCP. The values determined by the biotin–streptavidin–TRFIA and ELISA correlated well (R (2) = 0.8927). The method was applied to determine anti‐CCP in serum samples with satisfied recoveries of 96.45–104.63%. CONCLUSION: The assay results obtained by the present method showed that biotin–streptavidin‐amplified TRFIA improve the traditional ELISA kit for anti‐CCP detection. Therefore, it offers a better alternative immunoassay in rheumatoid arthritis management.

We demonstrate herein a novel time-resolved fluoroimmunoassay (TRFIA) with high sensitivity and wide range for quantitative detection of ANA-Ig(GAM) antibodies using a biotin-avidin amplification system. The immunoassay was conducted by following procedures for a typical sandwich immunoreactions with cell nucleus form Hela and the Eu(3+)-labeled biotin combined with biotinylated mouse anti-human Ig(GAM) served as the solid nuclear antigen for ANA and the tracer, respectively. The sensitivity, specificity, and stability of the kit were evaluated and comparison with the classical enzyme-linked immunosorbent assay (ELISA) kit was also made. The average intra-assay and interassay CVs detected by the established ANA-Ig(GAM) biotin-avidin-TRFIA were 4.21% and 6.34%, respectively. The lower detection limit was 2.24 U/mL, and the mean recovery rate was 100.74%. The good measurable range of the established biotin-avidin-TRFIA was within 1.95-64,000 U/mL, while it was only within 32.5-4000 U/mL using an ELISA kit. The values determined by the biotin-avidin-TRFIA and ELISA correlated well (R2 = 0.989). The positive rate of healthy volunteers and patients with systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), primary biliary cirrhosis (PBC), Sjogren's syndrome (SS), scleroderma, and mixed connective tissue disease (MCTD) was 0, 100%, 18.5%, 100%, 37.9%, 90.9%, and 92%, respectively. We conclude that the biotin-avidin-TRFIA we developed gives promise for greater sensitivity and accurate detection for ANA-Ig(GAM) in diagnosing and monitoring autoimmune disorders.

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.