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Objective:To study the patterns of tocilizumab (TCZ) use, its efficacy and safety in patients with rheumatoid arthritis (RA) in routine clinical practice.Methods:A total of 407 patients with RA were enrolled from 23 centers and treated with TCZ within 8 weeks prior to the enrollment visit, and were followed for 6-month. The patterns of TCZ treatment at 6 months, the effectiveness and safety outcomes were recorded. Statistical analysis was performed using SAS version 9.4.Results:A total of 396 patients were included for analysis, in which 330 (83.3%) patients received TCZ combined with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), and 16.7%(66/396) received TCZ monotherapy. At baseline, TCZ was initiated in 56.6%(224/396) and 9.6%(38/396) of patients after failure of DMARDs and other biological agents (bDMARDs) respectively. During the 6-month follow-up period, the mean frequency of TCZ administration was (3.7±1.6), the mean TCZ dosage was (7.4±1.2) mg/kg, and the mean interval between doses was (40±13) days. 120(25.8%) patients were on TCZ treatment at the end of the study. Improvements in disease activity, systemic symptoms and patient report outcomes were observed at the end of the study. 22.7%(90/396) patients experienced at least one treatment related adverse event, and 8 patients experienced at least one serious adverse event.Conclusion:This study demonstrates that TCZ treatment is effective in patients with RA when being treated for 6 months with an acceptable safety profile. The duration of TCZ treatment needs to be extended.
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Objective To explore the effects of leptin on the senescence of bone marrow-derived mesenchymal stem cells,frequencies of Treg and Th17 cells,and lupus disease in MRL/lpr mice,and to explore the pathogenesis of systemic lupus erythematosus (SLE).Methods Leptin (1 μg/g) or phosphate buffer saline (PBS) was injected into C57BL/6 (B6) mice,ob/ob mice and MRL/lpr mice intra-peritoneally.Urine protein was examined by Coomassie brilliant blue method.The levels of serum leptin,antinuclear antibody (ANA),anti-dsDNA antibody and immunoglobulin (Ig)G were detected by enzyme linked immunosorbent assay (ELISA).Bone marrow derived mesenchymal stem cells (MSCs) were isolated,and treated with or without leptin,then the senescence of MSCs were evaluated by SA-β-gal staining,the levels of p53 and p21 mRNA were measured by real time polymerase chain reaction (PCR),the protein levels of p53 and p21 were tested by Westem blotting method.Data were analyzed with t test and ANOVA.Results The level of serum leptin was higher in MRL/lpr mice than that of B6 mice [(4.5±0.8) ng/ml vs (2.3±0.5) ng/ml,t=2.38,P＜0.05].Leptin treatment in vivo accelerated the senescence of bone marrow-derived MSCs from all B6 mice,lupus mice and ob/ob mice,manifestedas increased frequencies of SA-β-gal positive cells [(20.6±0.6)％ vs (15.4±1.6)％,t=8.09,P＜0.05],higher levels of mRNA and p53 and p21 protein.Leptin treatment in vivo also down-regulated the frequency of Treg cells [(2.77±0.23)％ vs (5.01±0.18)％ t=3.91,P＜0.01],and up-regulated Th17 cells [(2.24± 0.11)％ vs (1.74±0.07)％,t=5.013,P＜0.01].The titer of ANA was further increased in leptin-treated MRL/lpr mice [(288±69) U/ml vs (190±90) U/ml,t=2.84,P＜0.05].The levels of serum anti-dsDNA antibody were also remarkably elevated [(12 399±1 237) U/ml vs (6 217±1 304) U/ml,t=3.44,P＜0.01].Leptin could increase the secretion of total IgG [MRL/Ipr (27.2±2.9) mg/ml vs (25.0±3.3) mg/ml,t=3.07,P＜0.05].The proteinuria concentration was increased in lupus mice [(1.00±0.10) mg/ml vs (0.81 ±0.06) mg/ml,t=3.31,P＜0.05],demonstrating that leptin accelerates lupus nephritis.Conclusion Leptin administr-ation in vivo enhances the senescence of bone marrow derived MSCs,dys-regulate of Treg/Th17 cells from MRL/Ipr mice,which impaires the role of immuno-modulation,and aggravates the progress of lupus disease.
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Objective To investigate the clinical significance of PET/CT in the diagnosis of giant cell arteritis .Methods The clinical manifestations ,laboratory detection and PET/CT results in 4 patients with giant cell arteritis treated in this hospital were retrospectively analyzed .And the relevant literatures were reviewed .Results The age of 4 cases in this hospital and 29 cases in lit-eratures all were over 50 years old ;clinical manifestations were mainly the non-specific symptoms such as fever ,weight loss and my-algia;the laboratory detection results mainly manifested by the increase of ESR and CRP ;PET-CT indicated that the continuous dif-fuse metabolism of the wall in aorta and its primary branching was elevated ;the maximal standardized uptake value(SUVmax) of 4 cases in this hospital was 2 .5-9 .6 .Conclusion PET/CT has a certain value for diagnosing giant cell arteritis ,especially the pa-tients with early stage or atypical clinical manifestations .PET/CT has certain significance for determining the lesion range and jud-ging the curative effect .
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Objective To retrospectively analyze the clinical features of elderly-onset systemic lupus erythematosus (SLE).Methods A total of 916 patients were enrolled in this retrospective study,and their clinical data were collected by the same methods in the past ten years (1999 2009) in fifteen hospitals in Jiangsu Province.Patients were divided into two groups based on the age of onset disease:control group and elderly group.The relationships between clinical features,immunology index and disease activity were analyzed in different age group.Results Among 916 SLE patients,24 patients were selected in the elderly onset SLE group,and 892 patients were considered as the control group.The ratio of male/female,mortality rate,the number of complications were higher in elderly onset SLE group than those in the control group (all P ＜ 0.05),and discoid rash,thrombocytopenia,elevated C-reactive protein (CRP) level,abnormality of serum albumin were found more common in elderly onset SLE group than in control group (all P＜0.05).The incidences of Malar rash and photosensitivity,antinuclear antibodies (ANA) positivity rate,anti-Sm antibodies positivity rate were lower in elderly onset SLE group than in control group (all P＜0.05).The time of final diagnosis,mean time of onset to death,positive family history,oral ulcers,arthritis,serositis,nervous involvement,musculoskeletal disorder,renal involvement,elevated serum creatinine (Scr) level,leucopenia,hemolytic anemia,elevated proteinurine,Erythrocyte Sedimentation Rate (ESR) levels,anti-dsDNA antibodies positivity rate,decreased complement C3 level,SLEDAl score had no significant differences between the two groups.Conclusions There were many differences in the clinical features between the elderly onset SLE patients and the controls,and the mortality rate is higher in the elderly onset SLE patients,which should be pay more attention to in clinical medcine.
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<p><b>BACKGROUND</b>Bone damage around the joints is one of the major pathophysiological mechanisms that leads to rheumatoid arthritis (RA) chronic disability. Serum tartrate-resistant acid phosphatase 5b (TRACP-5b) is secreted by osteoclasts, its activity can be used as a clinically relevant bone resorption marker. The aim of this study was to test whether the measurement of serum levels of TRACP-5b in patients with RA would correlate with measures of disease activity and with responses to therapy.</p><p><b>METHODS</b>Fifty-six patients were randomly assigned to receive recombinant human cytotoxic tlymphocyte-associated antigen-4 immunoglobulin (RhCTLA4-Ig), infliximab or methotrexate (MTX). The clinical and serologic indicators of RA activity were evaluated at baseline and at 24 weeks. Serum TRACP-5b was measured by Enzyme-linked Immunosorbent Assay (ELISA) at 0, 12 and 24 weeks. Hand X-rays were obtained at baseline.</p><p><b>RESULTS</b>At baseline, the levels of TRACP-5b correlated with the severity of X-ray damage, disease duration (r = 0.332, P = 0.012), and tender joint count (r = 0.408, P = 0.002). The 24 weeks values of TRACP-5b for RhCTLA4-Ig group and infliximab group differed significantly from the baseline values in each group (P < 0.05; P < 0.05), whereas only the value for RhCTLA4-Ig group differed significantly from the 24 weeks value for the MTX group (P < 0.01). Considering the two biologics-treated groups together, the TRACP-5b levels at 24 weeks differed significantly from the baseline values only in those patients who reached an ACR70 level (P < 0.05).</p><p><b>CONCLUSIONS</b>Measurement of serum TRACP-5b in RA patients reflects clinical and radiological measures of disease activity, treatment with certain biologics, and degree of response to therapy. TRACP-5b should be investigated further as a potential biomarker to predict response to therapy, including slowing of radiographic progression.</p>
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Adolescent , Adult , Female , Humans , Male , Middle Aged , Young Adult , Acid Phosphatase , Blood , Antibodies, Monoclonal , Therapeutic Uses , Arthritis, Rheumatoid , Blood , Drug Therapy , Biomarkers , Blood , Enzyme-Linked Immunosorbent Assay , Infliximab , Isoenzymes , Blood , Methotrexate , Therapeutic Uses , Osteoclasts , Metabolism , Pilot Projects , Tartrate-Resistant Acid PhosphataseABSTRACT
ObjectiveTo investigate the association of complement C3 with clinical and serological features of patients with systemic lupus erythematosus.MethodsData was collected by the same methods in the past ten years in fifteen hospitals in Jiangsu Province and then data weres summarized for retrospective analysis.Clinical and laboratory data were selected and then analyzed by Chi-square test,Wilcoxon rank sum test and Logistic regression.ResultsOne thousand four hundred and five patients were investigated.One thousand and forty two had low serum complement C3 level.In this case control study,hospitalization age,disease course,admission times,pleurisy,gastrointestinal involvement,general lymphadenopathy/hepatosplenomegaly,white blood cell count, haemoglobin level,platelet count, serum C-reactive protein level,serum albumin level,serum creatinine level,Urine protein quantification,anti-nuclear antibodies (ANA),anti-dsDNAantibodies, anti-SmantibodiesandSLEDAIscore were possible factors associatedwith complement C3 reduction(P＜0.05).Logistic regression analysis showed that CRP (OR=0.396,0.254-0.617,P=0.000),ANA (OR=2.907,1.267-6.670,P=0.012),urine protein level(OR=1.702,1.043-2.779,P=0.033) and SLEDAI score (OR-0.930, 0.886-0.975,P-0.003) were correlated with complement C3 reduction.Conclusion Complement C3 level is valuable for lupus flare assessment.The complement C3 reduction is a risk factor for renal impairment.
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Objective To detect the serum level of tartrate-resistant acid phosphatase 5b (TRACP5b) in patients with rheumatoid arthritis (RA) before and after infliximab treatment and analyze the relevance between TRACP-5b and activity indexes of RA.The effect of different medicines on bony erosion in RA and its possible mechanism were explored.Methods Patients were divided into two groups:16 patients were treated with inffiximab for 24 weeks (group 1 ),25 patients were treated with MTX for 24 weeks (group 2).The core indicators of RA activity were evaluated.Ranked test,grouped design and matched t test was used to examine the quantity data between groups,while numerate data was analyzed with qui-square test.Correlation between data was tested by Spearmen's and Pearson's tests.RestltsThe levels of TRACP-5b in patients with X-ray stagesⅠ ,Ⅱ ,Ⅲ ,Ⅳ were elevated at the baseline.The levels of TRACP-5b in phase Ⅲ and Ⅳ were [(3.34±1.07) U/L] and[(4.05±0.25) U/L] respectively,higher (P＜0.05) than those in phase Ⅰ[(1.69±0.48) U/L].At week 0,week 12,and week 24,the serum levels of TRACP-5b in group 1 were(3.07±1.32),(2.72±1.18),(2.16±1.09) U/L respectively,while the levels in week 12,and 24 were significantly lower than those of week 0(P＜0.05).A significant decrease of serum TRACP-5b level in group 1[(2.16±1.09 ) U/L]when compared to group two[ (3.05±0.93) U/L] after 24 weeks.TRACP=5b level was positively correlated with the course of disease (r=0.313,P=0.043 ),HAQ(r=0.443,P=0.007).Conclusion Infliximab can reduce TRACP-5b level in RA and inhibit inflammatory bone loss.TRACP-5b can be used to evaluate the efficacy of biological agents in treating RA.
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Objective To explore the relationship between the impairment of hematological system and disease activity,immunological parameters,and the prognosis of systemic lupus erythematosus (SLE).Methods The clinical and laboratory data of in-patients with SLE in Jiangsu Province were investigated and all patients were hospitalized between 1999-2009.The impairment of hematological system was assessed and the relationship between hematological system damage and disease activity,immunological parameters,mortality rate of patients with SLE were analyzed.Statistic method used was X2 test.Results One thousand nine hundred and fifty eight cases of SLE were included in the study,in which,1836 were female and 122 were male.One thousand five hundred and forty nine (79.1%) patients complicated with hematological system damage,62.3% were anemia,45.5% with leucopenia and 29.4% with thrombocytopenia.There were significant differences in hematological system damage rate among patients with mild activity group,moderate activity group,severe activity group and almost no activity group,compared respectively with almost no activity group.The P values were P=0.01 and P＜0.01 respectively.The incidence of hematological system damage in elevated ESR,low complement C3 level,anti-dsDNA antibody group was higher than that in patients who had normal ESR,complement C3 level and anti-dsDNA group.(P＜0.01).During follow-up,166 patients died,of which the mortality rate(91.6%) in patients had hematological system damage,was obviously higher than those without hematological damage(8.4%)(P＜0.01 ).Among the 166 deceased patients,38.6% died of severe infection,22.9% died ofrenal failure,15.1% died ofnervous system damage,10.2% died of cadiovascular damage and 13.3% died from other causes.Conclusion Hematological system is one of the most commonly involved system in patients with SLE,of which anemia is the most common,and the incidence of leukopenia follows.The impairment of hematological system is closely related to lupus activity.Patients with abnormal immune parameters tend to have secondary hematological system damage.Severe infection is the main cause of death in patients with lupus,followed by nervous system damage and kidney damage.The mortality rate in patients with lupus that complicated hematological system damage is higher than patients who have no hematological system damage.
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Objective To investigate the initial manifestation and disease onset feature of systemic lupus erythematosus(SLE) in the past ten years in fifteen hospitals in Jiangsu Province.Methods Data was collected by the same Methodsin all the participated hospitals and then it was summarized for retrospective analysis.Two groups were compared by chi-square test.Results ① One thousand nine hundred and fifty eight patients were investigated and the male-to-female ratio was 1∶15.0.② One thousand seven hundred and ninty eight patients had clear initial manifestations.The most common initial manifestations were skin and mucosal lesions(769 cases,42.8％ ) and arthritis (697 cases,38.8％ ).The main skin lesion was malar rash (706 cases).Arthritis was found to be more common in female than male.③ All hospitalized patients at their first admission showed multiple organ/system involvement:the most common involvement was skin and mucous membrane (82.3％),hematologic damage (74.0％),in which at least one series of blood cells were involved,arthritis (1156 cases,56.5％ ) much more than myositis (51 cases),proteinuria 1046 cases and hematuria in 385 cases.Renal biopsy pathology showed type Ⅳ glomerulonephritis.Conclusion ① SLE patients are mainly female and the male to female ratio is 1∶15.0.② The most common initial manifestations are skin and mucosal lesions.③ The most commonly involved organ/system are skin and mucous membrane,blood,joint and kidney.The most common pathological changes shown in renal biopsy is type Ⅳ glomerulonephritis.
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Objective To develop a method for detecting anti-cyclic citrullinated peptide (anti-CCP)in the serum of rheumatoid arthritis patients. Methods The range of lineage correlation, precision and detection range of time-resolved fluoroimmunoassay (TRFIA) was analyzed. Thirty-two positive serum of antiCCP, and the sera from 50 health blood donors, 32 SLE patients, 26 patients with SS, 10 patients with scleroderma, 20 patients with MCTD and 18 patients with MS were tested in this study. The clinical specificity was assessed. The consistency between TRFIA and ELISA was analyzed by Mc Nemar test. Results Analyzed by SPSS 13.0 statistical software, the intra-batch precision (n=20) rate was 2%, 3% and 4% respectively, and the inter-batch precision (n=8) was 3%, 4% and 7% respectively for 3 different concentrations. The clinical specificity was 98%, 97%, 96%, 100%, 95% and 100% in the sera of healthy blood donors, SL,E, SS,scleroderma, MCTD and MS patients respectively. The correlation coefficient was 0.989.The average recovery rate was 101%, and the sensitivity was 1 U/ml. When compared with ELISA, the detection range of TRFIA was wider and also with betterstability. Conclusion TRFIA is a stable method with high sensitivity and wide detection range. It can be used to detect anti-CCP antibody. It is important for early diagnosis of RA and monitor the curative effect of RA. And this method has potential to be used in clinical diagnosis.