Genome-wide DNA methylation patterns in monocytes derived from patients with primary Sjogren syndrome / 中华医学杂志(英文版)

BACKGROUND@#Epigenetics, especially DNA methylation, plays an important role in the pathogenesis of primary Sjogren syndrome (pSS). Our study aimed to reveal the role of DNA methylation in peripheral monocytes of pSS patients.@*METHODS@#A total of 11 pSS patients and five age-matched healthy controls (HCs) were included in this study. Monocytes were isolated from peripheral blood mononuclear cells using magnetic microbeads. DNA methylation profiles were generated using Human Methylation 850K BeadChips.@*RESULTS@#In monocytes from pSS patients, we identified 2819 differentially methylated positions (DMPs), comprising 1977 hypomethylated- and 842 hypermethylated-DMPs, corresponding to 1313 unique genes when compared with HCs. IFI44L, MX1, PAARP9, and IFITM1, which influence the interferon (IFN) signaling pathway, were among the genes hypomethylated in pSS. Functional analysis of genes with a minimum of two DMPs showed involvement in antigen binding, transcriptional regulation, cell adhesion, IFN-γ pathway, type I IFN pathway, antigen presentation, Epstein-Barr virus infection, human T-lymphotropic virus type 1 virus infection, and metabolic disease-related pathways. In addition, patients with higher serum IgG levels exhibited enrichment in Notch signaling and metabolic-related pathways. Upon comparing monocytes with salivary gland epithelial cells, an important overlap was observed in the cell cycle, cell senescence, and interleukin-17 signaling pathways. The differentially methylated genes were more enriched in the ribosome- and AMP-activated protein kinase signaling pathway in anti-Ro/SSA and anti-La/SSB autoantibodies double-positive patients.@*CONCLUSION@#Genome-wide DNA methylation profiling revealed significant differences in DNA methylation in monocytes isolated from patients with pSS.

Chinese Systemic Lupus Erythematosus Treatment and Research Group Registry IX: Clinical Features and Survival of Childhood-Onset Systemic Lupus Erythematosus in China / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Approximately 15-20% cases of systemic lupus erythematosus (SLE) are diagnosed in children. There have been a few studies reporting the epidemiological data of pediatric-onset SLE (cSLE) in China, neither comparing the differences between cSLE and adult-onset SLE (aSLE). The aim of this study was to describe the impact of age of onset on clinical features and survival in cSLE patients in China based on the Chinese SLE Treatment and Research group (CSTAR) database.</p><p><b>METHODS</b>We made a prospective study of 225 cSLE patients (aged Results: The mean age of cSLE patients was 12.16 ± 2.92 years, with 187 (83.1%) females. Fever (P < 0.001) as well as mucocutaneous (P < 0.001) and renal (P = 0.006) disorders were found to be significantly more frequent in cSLE patients as initial symptoms, while muscle and joint lesions were significantly less common compared to aSLE subjects (P < 0.001). The cSLE patients were found to present more frequently with malar rash (P = 0.001; odds ratio [OR], 0.624; 95% confidence interval [CI], 0.470-0.829) but less frequently with arthritis (P < 0.001; OR, 2.013; 95% CI, 1.512-2.679) and serositis (P = 0.030; OR, 1.629; 95% CI, 1.053-2.520). There was no significant difference in SLE disease activity index scores between cSLE and aSLE groups (P = 0.478). Cox regression indicated that childhood onset was the risk factor for organ damage in lupus patients (hazard ratio 0.335 [0.170-0.658], P = 0.001). The survival curves between the cSLE and aSLE groups had no significant difference as determined by the log-rank test (0.557, P = 0.455).</p><p><b>CONCLUSIONS</b>cSLE in China has different clinical features and more inflammation than aSLE patients. Damage may be less in children and there is no difference in 5- year survival between cSLE and aSLE groups.</p>

Lupus Myocarditis: A Case-Control Study from China / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Myocarditis is an uncommon but serious manifestation of systemic lupus erythematosus (SLE). This study aimed to investigate clinical characteristics and outcomes of lupus myocarditis (LM) and to determine risk factors of LM in hospitalized Chinese patients with SLE.</p><p><b>METHODS</b>We conducted a retrospective case-control study. A total of 25 patients with LM from 2001 to 2012 were enrolled as the study group, and 100 patients with SLE but without LM were randomly pooled as the control group. Univariable analysis was performed using Chi-square tests for categorical variables, and the Student's t-test or Mann-Whitney U-test was performed for continuous variables according to the normality.</p><p><b>RESULTS</b>LM presented as the initial manifestation of SLE in 7 patients (28%) and occurred mostly at earlier stages compared to the controls (20.88 ± 35.73 vs. 44.08 ± 61.56 months, P = 0.008). Twenty-one patients (84%) experienced episodes of symptomatic heart failure. Echocardiography showed that 23 patients (92%) had decreased left ventricular ejection fraction (<50%) and all patients had wall motion abnormalities. A high SLE Disease Activity Index was the independent risk factor in the development of LM (odds ratio = 1.322, P < 0.001). With aggressive immunosuppressive therapies, most patients achieved satisfactory outcome. The in-hospital mortality was not significantly higher in the LM group than in the controls (4% vs. 2%,P = 0.491).</p><p><b>CONCLUSIONS</b>LM could result in cardiac dysfunction and even sudden death. High SLE disease activity might potentially predict the occurrence of LM at the early stage of SLE. Characteristic echocardiographic findings could confirm the diagnosis of LM. Early aggressive immunosuppressive therapy could improve the cardiac outcome of LM.</p>

Tacrolimus therapy in refractory lupus nephritis: a prospective study in a single center / 中华风湿病学杂志

ObjectiveThe purpose of this study was to assess the efficacy,safety and optimal dose of tacrolimus monotherapy in patients with refractory lupus nephritis(LN) who were resistant to cyclophosphamide(CYC).MethodsA total of 14 LN patients (2 men and 12 women) with persistent proteinuria who were resistant to CYC treatment more than 8 g for half a year were enrolled.Tacrolimus was initiated at 2 mg/d (patient weight＜60 kg) or 3 mg/d(patient weight≥60 kg) which was administered in two divided doses.Prospective data on daily proteinuria,serum album level and serologic lupus activity were collected and followed for 6 months.ANOVA and Pearson correlation analysis were used for statistical analysis.Results Mean age at baseline was(30±9) years.Mean urinary protein decreased significantly from(6.2±5.1) g at baseline to (1.1±0.9) g at 6 months (F=16.21,P＜0.01).Mean serum album level increased significantly from (27.9±9.7) g/L at baseline to(37.8±2.2) g/L at 6 months(F=16.71,P＜0.01 ).Complete or partial response was observed in 86％ of patients receiving tacrolimus therapy.The effective dosage in this study was 0.03-0.06mg·kg-1·d-1 of the patients who had complete response or partial response to tacrolimus.The tacrolimus level in partially and completely responding patients was less than 3 ng/ml.There was no significant difference among blood tacrolimus levels of complete,partial,and no response patients [(1.6-±0.4),(2.0±0.6) and (22±1.1) ng/nl],respectively).No definite correlation was found between efficacy and tacrolimus level.Tacrolimus was well tolerated at current dose,besides one with new onset hypertension and one with alopecia.ConclusionOur results suggest that tacrolimus at low dosage and serum level is potentially effective and safe for the treatment　of patients with LN and persistent proteinuria resistant to CYC.The optimal dosage of tacrolimus for LN may　be 0.03-0.06 mg·kg-1·d-1.

Antiphospholipid syndrome: clinical and immunologic manifestation and patterns of disease expression in a cohort of 100 patients / 中华风湿病学杂志

Objective To analyze the clinical and immunological manifestations of antiphospholipid syndrome(APS)in a cohort of 100 patients.Methods The clinical and serologic features of APS(Sapporo preliminary criteria)in 100 patients were analyzed retrospectively.Results The cohort consisted of 79 female patients and 21 male patients witb a mean age of 36?13 years at diagnosis.Primary APS was presented in 37% of patients;APS was secondary to systemic lupus erythematosus(SLE)in 46%,lupus-like syndrome in 14%. Eighty percent of the patients had thrombosis,43(54%)patients had venous thrombosis,18(22%)had arterial thrombosis,15(19%)had both arterial and venous thrombosis.4(5%)had thrombosis of microcirculation. Forty-two(52%)patients presented thrombosis at a single site,26(32%)at two sites,12(15%)at three or more sites.Forty-five(56%)patients experienced one thrombotic episode,20(25%)patients had only one re- currence,and 15(19%)had more thrombosis.The most common manifestations of thrombosis were deep vein thrombosis(36%),pulmonary embolism(30%)and stroke(26%),with heart,kidney,gastrointestinal tract and other organs involvements.Thirty-four(51%)female patients had spontaneous fetal losses including intrauter- ine fetus death and recurrent spontaneous abortion.Seventy-one(71%)patients developed thromboeytopenia. The presence of antieardiolipin antibody(ACL)was detected in 84 patients(84%).Among 90 patients with APS,alone ACL was detected in 38 patients(42%),both ACL and lupus anticoagulant(LA)were detected in 36(40%),LA alone in 16(18%).Patients with APS associated with SLE or lupus-like syndrome had higher frequency of arthritis,leukopenia,antinuclear antibodies(ANA)and low complement levels.Female patients had a higher frequency of leukopenia,ANA and ACL.Male patients had a higher prevalence of deep venous thrombosis in the lower limbs and LA.Conclusion APS is an autoimmune disorder characterized by recurrent arterial and venous thrombosis,fetal loss,or thrombocytopenia with the presence of ACL and/or LA.In APS secondary to with SLE,the patient's sex can modify the disease expression and define specific subsets of APS.