Application of the 2016 European League Against Rheumatism/American College of Rheumatology/Pediatric Rheumatology International Trials Organization classification criteria for macrophage activation syndrome complicating systemic juvenile idiopathic arthritis in adult-onset Still disease / 中华风湿病学杂志

Objective In 2016,European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR)/Pediatric rheumatology international trials organization (PRINTO) released the classification criteria for macrophage activation syndrome (MAS) in patients with systemic juvenile idiopathic arthritis (sJIA).Due to the similarities of both clinical manifestations and pathogenesis between adult-onset Still dsease (AOSD) and sJIA,we hope to evaluate the 2016 sJIA-AMS classification in AOSD patients.Methods A total of 169 AOSD patients who were hospitalized in Renji Hospital were enrolled in this study.AOSD patients were divided into AOSD with MAS and AOSD without MAS,using the 2016 sJIA-MAS criteria.The data of the two groups were analyzed by Chi-square test,Mann-Whitney U test and binary Logistic analysis,and factors influencing the prognosis of patients were analyzed by Kaplan-Meier and COX regression analysis.Results According to sJIA-MAS criteria,56 AOSD patients with MAS were identified in all the 169 AOSD cases.In AOSD patients,the incidence of splenomegaly and pericarditis/myocarditis was significantly higher in patients with MAS than in AOSD without MAS [42.9％ vs 14.2％,OR(95％CI)=4.50(2.13,9.51),P＜0.01;10.7％ vs 0.9％,OR(95％CI)=13.21 (1.56,113.57),P＜0.01],also the incidence of liver dysfunction was higher in AOSD with MAS [67.8％ vs 11.5％,OR(95％CI)=0.18(7.26,36.33),P＜0.01].Among the AOSD with MAS,62.5％(35/56) of these patients received large-dose glucocorticoid therapy,5.4％ (3/56) received the glucocorticoid pulse therapy,48.2％(27/56) were treated with IVIG,and 26.8％(15/56) were treated with calcium phosphatase inhibitors.The mortality rates of AOSD with MAS was 8.9％(5/56),which was significantly higher than 1.8％(2/113) (OR =5.44,P＜0.05),the mortality rate of the AOSD without MAS.Patients who fulfilled the sJIA-MAS criteria suggested poor prognosis (OR=0.041,P=5.44),and the platelet count ≤ 181× 109/L (OR=12.17,P=0.002),alanine aminotransferase ＞48 U/L (OR=9.43,P=9.040) were also highly suggestive of poor prognosis.Conclusion The 2016 sJIA-MAS classification criteria are particularly valuable for early recognization of MAS in AOSD patients,and convenient to use.AOSD patients fulfilled sJIA-MAS criteria are more severe,and require larger doses of glucocorticoid and more immunosuppression therapy compared to patients without MAS,and the prognosis of these patients is also poor.

Systemic lupus erythematosus associated pulmonary arterial hypertension: results from 10-year inpatient cases analysis in a single center / 中华风湿病学杂志

Objective To investigate the clinical characteristics and current condition of treatment for systemic lupus erythematosus (SLE) associated pulmonary arterial hypertension (PAH).Methods 10-year inpatients cases were reviewed and followed up.Cases were divided into 2 groups:group A:patients with baseline pulmonary arterial systolic pressure (PASP) lower than 70 mmHg； group B:patients with baseline PASP higher than 70 mm Hg.Pearson's correlation analysis,Chi-square test,Logistic regression,Cox-Mantel and Wilcoxon test were used for statistical analysis.Results There were totally 155 cases with 184 records of admission which accounted for 4.16％ among total lupus cases.The main clinical characteristics included Raynaud's phenomenon (47.3％),pericardial effusion (41.9％) and high titer of anti-RNP antibody (55.4％).There were 132 cases enrolled for prognostic statistical analysis.There were 47 cases of death (35.6％) in total,among which 9 cases (19.1％) were in group A and 38 cases (80.9％) were in group B.In group A,there was a positive correlation between PASP and lupus disease activity index score.Single therapy analysis by Chi-square test showed that cyclophosphamide (CTX) (P＜0.05) and PAH targeted drugs (P＜0.01) were significantly associated with favorable outcome but logistic regressive analysis only confirmed the efficacy of target drugs (P＜0.01).PAH target drugs significantly improved the one year survival rate of the severe cases.Conclusion The main clinical characteristics of SLE associated PAH include Raynand's phenomenon,pericardial effusion and positive anti-RNP antibody.The severity of PAH may not be related to lupus disease activity.PAH targeted drugs are effective in SLE-PAH.CTX may be effective in some cases.For severe cases,the combination therapy of CTX and PAH targeted drugs could significantly improve the prognosis.

Evaluation of the clinical and radiological.efficacy of recombinant human TNFR Ⅱ -Fc combined with methotrexate in the treatment of moderate and severe rheumatoid arthritis / 中华风湿病学杂志

ObjectiveTo evaluate the clinical and radiological efficacy of TNFR Ⅱ -Fc combined with methotrexate( MTX ) in treatment of patients with moderate and severe rheumatoid arthritis.MethodsThree hundred and ninty-six RA patients were randomized into the combined treatment group,the TNFR Ⅱ -Fc only group and MTX only group.All patients were treated for 24 weeks.ACR-N,ACR20,ACR50,ACR70,DAS28-ESR and Sharp score of both hands were measured for efficacy,and the side-effects were analyzed by one-way ANOVA.Results After 24-week therapy,the ACR-N of the combined treatment group [( 12.79±9.24)％-year] was significantly improved than that of the TNFR Ⅱ-Fc only group [(9.56±11.16)％-year,P＜0.05] and that of the MTX only group[(5.08±11.10)％-year,P＜0.05],and the TNFR Ⅱ-Fc group was significantly improved than that of the MTX group(P＜0.05).The ACR20 response rate of the combined group(80.4％) was significantly higher than that of the TNFR Ⅱ -Fc group(71.1％,P＜0.05) and the MTX group(56.7％,P＜0.01 ).The ACRS0 response rate of the combined group(53.6％) was significantly higher than that of the MTX group(30.8％,P＜0.01 ).The ACR70 response rate of the combined group was 27.7％,which was significantly different from that of the TNFR Ⅱ -Fc group (15.8％) and MTX group (7.7％,P＜0.05or P＜0.01 ).DAS28-ESR in the combination group was significantly reduced than those of the TNFR Ⅱ -Fc group and MTX group,and the DAS28-ESR of the TNFR Ⅱ -Fc group was significantly reduced than MTX group.The average total Sharp score of both hands,which demonstrated the radiographic changes,was significantly reduced in the combination group than the MTX group(P=0.03).The total adverse events in the combined group(40.9％) was significantly high than that of the MTX group(28.8％,P＜0.05).Conclusion TNFR Ⅱ -Fc combined with MTX can effectively control the activity of RA and radiological progress.

The expression of IKB kinase in the peripheral blood and its correlation with the production of interferon-α in systemic lupus erythematosus patients / 中华风湿病学杂志

Objective To investigate the mRNA expression of IKB kinase (IKK-α) and interferon-α (IFN-α) in the peripheral blood leukocytes of patients with systemic lupus erythematosus (SLE), and to explore the role of IKK-α in the production of IFN-α in SLE patients. Methods SYBR green dye I based real-time quantitative PCR was used to detect the mRNA expression levels of IKK-α and IFN-α in the peripheral blood leucocytes of SLE patients and healthy controls. Serum levels of IFN-α were measured with ELISA method. Results IKK-α mRNA expression levels in SLE patients were significantly higher than those of normal controls (P<0.05). IKK-α mRNA expression levels in SLE patients with active disease were significantly higher than patients with stable disease (P<0.01). IFN-α mRNA expression level in SLE patients was significantly lower than that of the normal controls (P<0.01). IFN-α mRNA expression levels in SLE patients with active disease were significantly higher than patients with stable disease (P<0.01). Serum levels of IFN-α in SLE patients with active disease was significantly higher than that of the normal controls and patients with stable disease (P<0.05). The anti-dsDNA antibody correlated positively, and complement C3 correlated negatively with serum concentration of IFN-α. IKK-α mRNA expression levels in SLE patients correlated positively with serum concentration of IFN-α. Conclusion IKK-α correlates positively with serum concentration of IFN-α. The IFN-α level is significantly correlated with disease activity, This suggests that IKK-α may play an important role in the pathogenesis of SLE.

The relationship of vitamin D endocrine system and estrogen receptor expression with bone mineral density in initial systemic lupus erythematosus / 中华内科杂志

Objective To study the incidence of osteopenia in patients with initial systemic lupus erythematosus(SLE). Investigate the levels of the vitamin D (VitD) endocrine system in peripheral blood of SLE patients and its relation to bone mineral density (BMD). Analyse the relationship between the estrogen receptor (ER) and BMD and evaluate the role of ER in the pathogenesis osteopenia. Methods Serum levels of 25-OH VitD_3 and 1,25-(OH)_2 VitD_3 were detected by enzyme linked immunosorbent assay. The gene expression levels of VitD receptor (VDR) and ER were determined by real-time PCR. BMD measurements in the lumbar spine (L1-L4) and left proximal femur (femoral neck) were performed using dual X-ray absorptiometry before treatment. Results The initial SLE patients had significantly lower BMD values, and higher frequency of bone loss at both sites of measurement compared with normal controls (P < 0. 05). The levels of 25-OH VitD_3 and 1,25-(OH)_2 VitD3 were lower in the initial SLE patients than normal controls(P<0.01 both). There is no difference in the levels of 25-OH VitD_3 and 1,25-(OH)_2 VitD_3 between the osteopenia SLE group and the normal BMD SLE group (P > 0. 05, P > 0. 05). There are no correlations between the Vitd and BMD in initial SLE patients (P>0.05 both). The expressions of VDR gene were significantly increased in the initial SLE patients compared with the normal controls(P<0.01). There was no difference in VDR gene expression between osteopenia SLE group and normal BMD SLE group (P>0.05). The VDR gene expression does not correlate with the bone mass (P>0.05). The levels of ER-β gene expression are higher in the initial SLE group than the normal controls (P<0.01).Conclusions The incipient SLE patients may have lower BMD than expected. SLE patients present abnormal VitD endocrine system and higher ER-β mRNA expression than those in normal controls, but these weren't concerned with osteopenia.

The relationship between disease-related risk factors and premature atherosclerosis in systemic lupus erythematosus / 中华风湿病学杂志

Objective To evaluate the prevalence of atherosclerosis in Chinese premenopausal women with systemic lupus erythematosus (SLE) and study possible associations between non-traditional risk factors with premature atherosclerosis. Methods One hundred and eleven premenopausal women with SLE and 40 healthy controls without clinical cardiovascular disease were evaluated. B-mode ultrasonography was used to measure carotid plaque and intima-media wall thickness( IMT). The relationship between the patients' clinical characteristics and carotid plaque was examined. At the same time, B-mode ultrasound was used to measure flow-mediated dilation (FMD) and nitroglycerin-mediated dilation (NMD) in the brachial artery. Using this method, the difference in endothelial function between SLE patients and controls was assessed. T-test,χ2 test and logistic regression were used for statistical analysis. Results Carotid plaque was more frequently observed in patients with SLE (16 of 111 patients) than in control subjects (0 of 40 subjects) (P=0.007). The mean IMT (m-IMT) (0.62 mm vs 0.45 mm, P<0.01) and maximum IMT(M-IMT) (0.7 mm vs 0.6 mm, P<0.01) was significantly higher in patients than in controls. As compared with patients without plaque, patients with plaque were significantly older, had longer disease duration, higher body mass index (BMI), higher blood pressure, shorter prothrombin time, elevated C-reactive protein level, higher SLICC score, higher cumulative prednisone dose, less hydroxychloroquine accumulated dosage, higher m-IMT and M-IMT, lower FMD and NMD. In logistic regression analysis, older age (P=0.012, OR=1.137), higher BMI (P=0.051, OR=1.205) and higher SLICC score (P=0.000, OR=2.888) were independently related to the presence of plaque. Conclusion SLE patients have higher prevalence of carotid atherosclerosis plaque than healthy controls and the age at onset is younger than controls. In addition to traditional risk factors for cardiovascular disease, SLE itself and disease related factors play important roles in premature atherosclerosis in SLE. SLE patients have significant endothelial dysfunction. Thus, endothelial dysfunction can be regarded as one manifestation of premature atherosclerosis in SLE.

Infective endocarditis with positive anti-neutrophil cytoplasmic antibodies: three cases report with literature review / 中华风湿病学杂志

Objective To analyze the clinical features of infective endocarditis with positive antineutrophil cytoplasmic antibodies ,and compare with ANCA associated small vessel vasculitis(AASV). Methods Three IE patients with positive ANCA were analyzed, and 13 cases from literatures were reviewed. Results Sixteen patients had positive anti-PR3 ANCA, in which 2 cases had both positive (anti-PR3 and anti-MPO ANCA) ANCA. All patients had some clinical manifestations mimic AASV, including fever ( 13/16, 81% ), rash (8/16, 50% ), rapidly progressive glomerulonephritis (7/16, 44% ), splenomegaly (6/16, 38% ). Streptococcal species were identified in 12 patients, and cardiac valvular abnormalities were demonstrated in all patients. All patients except 2, who died of cerebral hemorrhage followed by cerebral infarction, recovered with antibiotic therapy. Conclusion Infective endocarditis sometimes can have the same clinical features as AASV, so physicians should carefully differentiate between them when dealing with patients with positive ANCA antibodies.

The significance of the vitamin D anti vitamin D receptor In the initial systemic lupus erythematosus patients / 中华风湿病学杂志

Objective ① To investigate the level of the vitamin D endocrine system in peripheral relationships with bone mineral density (BMD) and the disease activity respectively. Methods The level of the 25-hydroxylate vitamin D3 (25OHD3) and 1,25-dihydroxyvitamin D3 [1,25(OH)D3] in plasma from 43 SLE patients and 44 normal controls were detected by enzyme linked immunosorbent assay. Vitamin D receptor (VDR) gene expression was determinied by real-time PCR in peripheral blood. BMD measurements in the lumbar spine (L1-4) and left proximal femur (femoral neck) were performed using dual X-ray absorptiometry before treatment. The relationship between the vitamin D endocrine system and the bone mass were studied. We also discussed the relationship between the vitamin D endocrine system and the disease activity. Results The levels of 25OHD3 and 1,25 (OH)2D3 were lower in the initial SLE patients than normal controls (P<0.01, P<0.01). The expressions of VDR gene were significantly increased in initial SLE compared with normal controls (P<0.01). The initial SLE patients had significantly lower BMD values, and higher frequency of osteopenia (35%) at both sites of measurement compared with matched healthy controls (P<0.01). The initial SLE patients were divided into two groups by BMD, abnormal group and normal group. There were no differences in 25OHD3, 1,25 (OH)D3 and VDR gene expression (P0.05). There was no correlation between the vitamin D endocrine system and BMD in initial SLE patients. There was no correlation between the vitamin D endocrine system and the disease activity either. Conclusion Vitamin D endocrine system may play an important role in SLE, but the level of VDR gene is not correlated with BMD and disease activity.

Building-up and verification of the differential gene expression profile of peripheral blood leukocytes in Beh(c)et's disease / 中华风湿病学杂志

Objective To explore the pathogenic genes relevant to Behcet's disease (BD) by building the differentail gene expression profiles of peripheral blood leukocytes in BD. Methods Oligonucleotide gene array from Affymetrix Company was applied to study the differed expression levels of whole genome between three age and sex matched BD patients and normal controls. Four genes, BCL6, LRAP, ICOSLG and MME, were selected to be tested for gene expression levels by real-time PCR in the groups of BD, normol controls (NC), Lupus and rheumatoid arthritis (RA) peticnts. Results ① Differential gene expression profile of BD compared to that of normal controls was built up. It contained 89 up-regulated and 57 down-regulated genes. ② Four genes mentioned above had significantly higher expression levels in active BD patients than those in NC but had lower exoression levels in stable BD patients. The expression levels of BCL6 and MME were also proved to be increased significantly in BD than in RA and SLE patients. Conclusion ① Our work shed some light on further research of the etiopathogenesis of BD. ② The expression levels of the four genes are proved to be relevant to BD the first time by us. Further analysis showes that TNF-α and IFN-γ can up-regulate the expression levels of BCL6, LRAP and ICOSLG which may be novel to BD. The MME gene is expressed on the surface of cells, which is convenient for test and may potentially be a marker for the diagnosis of BD.

Treatment of ankylosing spondylitis with a recombinant human tumor necrosis factor receptor-Fc fusion protein: a multicenter, randomized, double blind, controlled trial / 中华风湿病学杂志

Objective To evaluate the efficacy and safety profile of a recombinant human tumor necrosis factor receptor: Fc fusion protein in ankylosing spondylitis (AS). Methods This was a multicenter,randomized, double-blind, placebo-controlled trial in the first 6 weeks and then followed by an open-labeled trial in the next 6 weeks. One hundred and forty-three patients of active AS were randomly assigned to receive 25 mg twice-weekly subcutaneous injections of rhTNFR:Fc or placebo for 6 weeks. The primary endpoint was proportion of ASAS20 responders at week 6. The secondary endpoints were the proportion of subjects achieving a BASDAI 20%, BASDAI 50% and BASDAI 70% improvement at week 6. Other secondary endpoints, related to reducing signs and symptoms of AS and improving range of motion and physical function, were evaluated.Results Treatment with rhTNFR:Fc resulted in significant improvement. At 6 weeks, 68% of the 71 patients in the rhTNFR: Fc group had a treatment response, as compared with 28% of those in the placebo group(P＜0.01). Improvements over base-line values for other measures of disease activity were significantly greater in the rhTNFR:Fc group, rhTNFR:Fc was well tolerated, The most frequently treatment related adverse event was injection site reaction. Conclusion rhTNFR:Fc has demonstrated consistent evidence of efficacy and is well tolerated in the treatment of active AS.

Chemokine score is a novel biomarker for lupus patients with active diseases and organ damages / 中华风湿病学杂志

Objective To correlate the chemokine score with disease activity,organ damages and clinical features in systemic lupus erythematosus (SLE) patients.Methods Peripheral blood cells obtained from 60 SLE patients,20 rheumatoid arthritis (RA) patients and 23 healthy donors (HDs) were subjected to real-time PCR to measure the transcriptional levels of seven chemokines (RANTES,MCP-1,CCL19,MIG,IP-10,CXCL11,and IL-8).Chemokine scores were calculated and were compared between various groups of SLE patients as well as between patients and controls.Results Chemokine scores were significantly elevated in SLE patients compared with RA patients and HDs (P=0.0112 and P=0.0019,respectively).Chemokine scores were correlated positively with SLEDAI (P=0.0061) and negatively with C3 levels (P=0.003).Compared to patients without lupus nephritis (LN),chemokine scores were elevated in SLE patients with active LN,especially when their daily prednisone dosage was less than 30 mg (P=0.0418 and P=0.002,respectively).Chemokine scores were also associated with cumulative organ damage (SLICC damage index [SDI]＞0) and positive anti-Sm and anti-RNP autoantibodies.Conclusion The chemokine score may serve as a new biomarker for disease activity and organ damage in SLE patients.

Leflunomide, a new disease-modifying drug for treating active rheumatoid arthritis in methotrexate-controlled phase II clinical trial / 中华医学杂志(英文版)

<p><b>OBJECTIVE</b>To evaluate the efficacy and safety of leflunomide in comparison with methotrexate (MTX) on patients with rheumatoid arthritis (RA) in China.</p><p><b>METHODS</b>Five hundred and sixty-six patients with active rheumatoid arthritis were randomly assigned to receive leflunomide at 20 mg once daily or MTX at 15 mg once weekly in a controlled trial. Five hundred and four patients completed the 12-week treatment and some patients continued the treatment for 24 weeks.</p><p><b>RESULTS</b>Both leflunomide and MTX could improve the symptoms, signs, and joint function, but there were no changes in X-ray observations of patients with rheumatoid arthritis. In the leflunomide group, the overall rates of effectiveness at 12 weeks and 24 weeks were 86.94% and 92.31% respectively; the rates of remarkable improvement were 64.95% and 79.81% respectively. In the MTX group, the overall rates of effectiveness at 12 weeks and 24 weeks were 84.04% and 83.15% respectively; the rates of remarkable improvement were 56.81% and 75.28% respectively. According to intent-to-treat analysis, the ACR 20% response rates at 12 weeks and 24 weeks in the leflunomide group were 62.54% and 67.18% respectively, compared with 60.08% and 61.32% respectively in MTX group. No statistical differences were shown in the efficacy between the two groups (P > 0.05). The adverse events in the leflunomide group were gastrointestinal symptoms, skin rash, alopecia, nervous system symptoms, decreased leukocyte count, and elevation of alanine aminotransferase (ALT). Most of these side effects were mild and transient. The incidence of adverse events in the leflunomide group was 16.84%, significantly lower than that in MTX group (28.17%, P = 0.002).</p><p><b>CONCLUSIONS</b>Leflunomide is effective in the treatment of RA with less adverse events than MTX. Its efficacy is similar to MTX, but the incidence of adverse events and the rate of withdrawal due to adverse events were lower in the leflunomide group than in MTX group.</p>

Transfection, overexpression and clinical application of human 60 kDa Ro/SSA autoantigens in HEp-2 cells / 中华医学杂志(英文版)

<p><b>OBJECTIVE</b>To develop an improved substrate for indirect immunofluorescence test (IIF) for detecting anti-Ro60/Sjogren's syndrome A (Ro/SSA) autoantibodies.</p><p><b>METHODS</b>60-kDa Ro/SSA autoantigens (Ro60) cDNAs were obtained from human placental cDNA library using polymerase chain reaction (PCR) and were cloned into the mammalian expression vector-pEGFP-C1. Then, the recombinant plasmids were transfected into HEp-2 cells. We confirmed the overexpression, localization and antigenicity of fusion proteins in transfected cells by means of immunoblotting, confocal fluorescence microscopy and IIF. HEp-2 and HEp-Ro60 were analyzed by IIF using a panel of 10 precipitin-positive anti-Ro human sera simultaneously.</p><p><b>RESULTS</b>Stable expression of Ro60-green fluorescent protein (Ro60-GFP) fusion proteins were maintained ten more generations. Ro60-GFP kept the antigenicity of Ro while demonstrating its own characteristic immunofluorescent pattern in HEp-Ro60 cells. The transfectants dramatically increased the sensitivity of IIF testing (a mean increase of 6.7-fold in endpoint titer). Eight over ten (8/10) positive anti-Ro sera showed characteristic immunofluorescent patterns for HEp-Ro60, including two sera that were anti-nuclear antibodies (ANA) negative for untransfected HEp-2. IIF-ANA in all healthy sera was negative for HEp-Ro60.</p><p><b>CONCLUSIONS</b>As a new substrate for IIF, the Ro60 transfectants can be used to detect anti-Ro antibodies. In addition, transfected HEp-2 cells keep the immunofluorescent properties of HEp-2 cells in IIF-ANA tests and can be employed as a substrate for routine IIF-ANA detection.</p>

Abnormal Th cell differentiation associated gene expression in systemic lupus erythematosus patients / 中华风湿病学杂志

Objective To continue to study if there is any other pathogenic gene expression related to Th1/Th2 abnormal differentiation,based on the author′s previous results,which have shown that Th1/Th2 unbalance is due to the cytokines and cytokine receptors of differentiation.Methods TaqMan Real time PCR was used to detect the gene expression of Th1/Th2 control in recent onset systemic lupus erythematosus (SLE) patients ( n =38).The genes include I?B,IRF 1,STAT4,GATA3,IL 4R and the others such as CCR1,CCR2,CCR4,CCR5,caepase 1 and CD38,which participate in inflammation,cell apoptosis and so on.Rheumatoid arthritis (RA) patients ( n =50) and normal people ( n =28) were control groups.Results ① Resent onset SLE patients comparing to normal people:STAT4 expression in IL 2/IL 12R ? 2/STAT4 access which induced Th1 differentiation increased significantly ( P 0 05) ;GATA3 expression which induced Th2 differentiation in IL 4/IL 4R/GATA3 access decreased significantly ( P

The significance of increased level of glucose-6-phosphate isomerase in rheumatiod arthritis patients / 中华风湿病学杂志

Objective To assess the clinical significance of glucose-6-phosphate isomerase in RA patients. Methods The level of serum GPI in 100 patients with RA, 98 patients with other rheumatic diseases and 108 normal controls were assessed by sandwich ELISA methods. The level of RF, CRP, anti-CCP antibodies were also assessed in RA patients. Results The level of GPI was higher in RA patients [(2.4?5.0) ?g/ml] than that of normal control group [(0.12?0.14) ?g/ml (P

Gene Expression Profiles of Peripheral Blood in a Family with Systemic Lupus Erythematosus / 中华皮肤科杂志

Objective To investigate the pathogenesis of familial systemic lupus erythematosus (SLE), by analyzing the gene expression profile of peripheral blood in a family with 2 SLE patients and their first-degree relatives. Methods Total RNA was extracted from peripheral blood cells of normal subjects and SLE patients. Then, synthesis double strand cDNA template from total RNA, transcription of cRNA probe with Biotin labeling, hybridization of probe with Microarray, binding of Streptavidin to Biotin, amplification with First Antibody, further amplification with Cy3-Conjugated Second Antibody, detection of Cy3 dye with ScanArray 5000 were performed. With QuantArray microarray analysis software, the scan image information was converted into numeric data. With GeneSpring microarray analysis software, cluster analysis was done to find interested genes. Results Over 3000 target genes were analysed. Fifty-nine genes differentially expressed in familial SLE patients and controls were identified. Among them, 34 genes were up-regulated and 25 genes were down-regulated. These differentially expressed genes identified in two familial SLE patients were almost identical to those found in other sporadic SLE patients. Among 34 expression increasing genes, 22 were up-regulated in SLE sisters and unaffected sisters; among 25 expression decreased genes, 17 genes down-regulated in SLE sisters and unaffected sister. Cluster analysis showed that patients were clearly separated from controls and their unaffected sisters based on their gene expression profile. These results showed that in familial SLE, multiple genes were responsible for susceptibility to SLE, and clinically unaffected relatives shared some lupus susceptibility genes with their clinically affected relatives, in addition environmental factors were probably necessary to trigger disease. Conclusion These results indicate that high-density oligonucleotide microarray has the potential to explore the heredity in SLE families.

Expression of Th1/Th2and Their Regu latory Cytokines in Systemic Lupus Erythematosus / 中华皮肤科杂志

0.05).However,Th1was decreased significantly in S LE patients than that in the normal controls(P