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Yunyun Fei,
Xuemei Li,
Sen Lin,
Xiaojun Song,
Qingjun Wu,
Yanlin Zhu,
Xin Gao,
Wen Zhang,
Yan Zhao, Xiaofeng Zeng,
Fengchun Zhang
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ABSTRACT: Behçet's disease (BD) is a multi-systemic inflammatory disorder which can affect all types and sizes of blood vessels. This study aims to evaluate the prevalence and characteristics of vascular involvement in BD. Among 796 patients diagnosed with BD, 102 patients (81 male, 21 female) with vascular involvement were included, whose detailed clinical characteristics were recorded. The diagnosis of vascular lesions was made on clinical signs, by Doppler ultrasonography, and/or angiography using computed tomographic or magnetic resonance techniques. Vascular involvement occurred in 12.8 % of BD patients. Male to female ratio was 3.86:1. Mean age at onset of vascular involvement was 29.5 ± 11.3 years. Vascular lesion was the initial sign of BD in 28 patients, accounting for 27.5 %. Of 102 BD patients with vascular involvement, 72 had venous lesions (70.6 %) and 56 had arterial lesions (54.9 %), among which 26 (25.5 %) patients had both venous and arterial involvements. Female BD patients were more often involved with arterial lesions, whereas male BD patients developed venous lesions more often than females, P = 0.000. The most common type of vascular involvement was deep venous thrombosis in lower extremities (n = 49), other affected venous sites including inferior vena cava, superior vena cava, and cerebral venous. The prominent type of arterial lesions was dilatation (n = 25, including 24 cases of aneurysms); other types included eight cases of occlusion and 23 cases of stenosis. The main locations of arterial lesions were the aorta (n = 19), lower extremity arteries (n = 15), pulmonary arteries (n = 13), coronary arteries (n = 5), and subclavian arteries (n = 5). Compared with those without vascular lesions, ocular involvement, genital ulcers, and arthritis were significantly less frequent among patients with vasculo-BD (23.5 vs 35.2 %, P = 0.024; 54.9 vs 76.5 %, P = 0.000; 19.6 vs 30.5 %, P = 0.026), whereas a higher frequency of cardiac involvement was found in vasculo-BD patients (20.6 vs 3.6 %, P = 0.000). Vascular involvement is a complication in BD patients. This study illustrated that venous lesions are more frequently involved than arterial lesions. Vascular lesions correlated with a high frequency of cardiac involvement and a low incidence of ocular lesions, genital ulcers, and arthritis.
Clinical Rheumatology 02/2013; · 2.00 Impact Factor
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ABSTRACT: OBJECTIVES: This study aimed to explore miRNA expression profiles in peripheral blood mononuclear cells (PBMCs) from patients with systemic lupus erythematosus (SLE) and the potential biological functions of the associated miRNA in the pathogenesis of SLE. METHODS: Fifty patients with active SLE and 26 healthy controls were enrolled. Four patients and four controls were used for miRNA microarray analysis to detect the levels of 847 miRNAs in PBMCs. The others were used for qRT-PCR confirmation and miRNA functional studies. A reporter gene assay was used to determine the biological function of miR-125b. RESULTS: Eleven miRNAs were found to be up-regulated and 26 miRNAs were down-regulated in SLE patients. Further analysis showed that the down-regulation of miR-125b, mainly in T cells, was negatively correlated with lupus nephritis. We also confirmed that ETS1 and STAT3 are target genes of miR-125b using a dual-luciferase reporter transfection assay. CONCLUSIONS: These data identified this miRNA expression profile as a possible new biomarker of SLE. Moreover, the down-regulation of miR-125b mainly in T cells may contribute to the pathogenesis of SLE by regulating ETS1 and STAT3 gene expression.
Clinical and experimental rheumatology 01/2013; · 2.15 Impact Factor
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ABSTRACT: PURPOSE: The study was designed to evaluate the efficacy and safety of lesser trochanteric osteotomy for femoral shortening in total hip arthroplasty in treatment of 28 cases of CROWE IV developmental dysplasia of the hip (DDH). METHODS: Patients underwent progressive femoral shortening at the level of lesser trochanteric to make reduction possible into the anatomical acetabulum in all hips. The results were collected and evaluated clinically and radiographically. RESULTS: The mean follow-up period was 55.3 months. The average postoperative leg length discrepancy was eight millimetres for unilateral THA patients. A modified Merle d'Aubigné scale was improved from 9.3 preoperatively to 15.9 postoperatively. Sciatic nerve palsy was confirmed in two hips which resolved completely in six months. The Trendelenburg sign was positive in two hips at the final follow-up. No revision surgery was required by the final follow-up. CONCLUSION: Lesser trochanteric osteotomy proved to be safe and effective in femoral shortening for treatment of CROWE IV DDH without the problem of nonunion at the site of osteotomy.
International Orthopaedics 01/2013; · 2.03 Impact Factor
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Yunyun Fei,
Qingjun Wu,
Wen Zhang,
Hua Chen,
Yong Hou,
Dong Xu,
Mengtao Li,
Xuan Zhang,
Yan Zhao, Xiaofeng Zeng,
Fengchun Zhang
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ABSTRACT: OBJECTIVES: This study aims to assess the efficacy and safety of low-dose tacrolimus therapy in patients with refractory lupus nephritis (LN) who were resistant to cyclophosphamide (CYC). METHODS: A total of 26 LN patients (4 men and 22 women) with persistent proteinuria who were resistant to CYC treatment (>8 g in less than 6 months) were enrolled. Tacrolimus was initiated at 2 mg/day (if patient weight <60 kg) or 3mg/day (if patient weight ≥60 kg), administered in two divided doses. Prospective data on daily proteinuria, serum albumin level, and serologic lupus activity were collected for 6 months. RESULTS: Mean age at baseline was 29.36±9.45 years. Mean urinary protein significantly decreased from 6.91±4.50 g at baseline to 1.11±1.10 g at 6 months (p<0.001). Mean serum album level significantly increased from 25.56±7.94 g/L at baseline to 38.12±2.42 g/L at 6 months (p<0.001). Mean systemic lupus erythematosus disease activity index (SLEDAI) score decreased from 11.42±6.74 at baseline to 3.61±2.73 at 6 months (p<0.001). Complete or partial response was observed in 88.46% of patients receiving tacrolimus therapy at 6 months. Twenty-one patients achieved partial or complete remission in two months. There was no significant difference among tacrolimus levels for patients with complete, partial, or no response. The effective dosage in this study was 2-3 mg/day for patients with complete or partial response to tacrolimus. Tacrolimus was well tolerated at the administered dose, though one patient developed severe lung infection. CONCLUSIONS: Our results suggested tacrolimus at low dosage and serum level to be potentially effective and safe for treatment in patients with LN resistant to sufficient CYC therapy. A tacrolimus dosage of 2-3 mg daily appears to be effective and safe.
Clinical and experimental rheumatology 08/2012; · 2.15 Impact Factor
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Yu Tang,
Hao Xie,
Jinyun Chen,
Linyu Geng,
Haifeng Chen,
Xia Li,
Yayi Hou,
Liwei Lu,
Songtao Shi, Xiaofeng Zeng,
Lingyun Sun
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ABSTRACT: Osteoporosis in patients with systemic lupus erythematosus (SLE) is thought to be the result of accelerated osteoclastogenesis induced by pro-inflammatory cytokines such as tumor necrosis factor (TNF). However, the molecular mechanisms involved in the osteoblastogenesis in SLE patients are not fully understood. We investigated the bone morphogenetic protein-2 (BMP-2)-induced osteoblastic capacity of bone marrow-derived mesenchymal stem cells (BMMSCs) from SLE patients and the TNF signaling system in determining BMP-2-induced regulatory pathways. It showed that the capacity of osteogenic differentiation of BMMSCs from SLE patients was reduced compared with that from healthy controls. The nuclear factor κB (NF-κB) signaling was activated while the BMP/Smad pathway was repressed in BMMSCs from SLE patients. TNF activated NF-κB pathway and inhibited the phosphorylation of Smad 1/5/8 and BMP-2-induced osteoblastic differentiation in BMMSCs from normal controls, while addition of pyrollidine dithiocarbamate (PDTC), an NF-κB inhibitor, to SLE-BMMSCs could partially reverse these effects. Thus, our findings have shown that the activated NF-κB pathway in SLE-BMMSCs inhibits the BMP-2-induced osteoblastic differentiation through BMP/Smad signaling pathway, suggesting that the impaired osteoblastic differentiation may participate in the pathology of osteoporosis in SLE patients.
Stem cells and development 08/2012; · 4.15 Impact Factor
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ABSTRACT: The quantitative identification and enrichment of viable regulatory T cells (Treg) requires reliable surface markers that are selectively expressed on Treg. Foxp3 is the accepted marker of nTreg, but it cannot be used to isolate cells for functional studies. In this study, we compared four staining profiles of Treg, including CD4(+)CD25(high) T cells, CD4(+)CD39(+) T cells, CD4(+)CD73(+) T cells, and CD4(+)CD25(+)CD127(low/-) T cells. We found that CD4(+)CD25(+)CD127(low/-) T cells expressed the highest level of Foxp3 and had the strongest correlation with CD4(+)CD25(+)Foxp3(+) T cells, the accepted identifying characteristics for "real" nTreg cells. Moreover, functional data showed that CD4(+)CD25(+)CD127(low/-) T cells could effectively suppress the proliferation of CD4(+)CD25(-) T cells, suggesting that compared with the other three populations, CD4(+)CD25(+)CD127(low/-) T cells best fit the definition of naturally occurring regulatory T cells in human peripheral blood. Finally, we showed that CD4(+)CD25(+)CD127(low/-) can be used to quantitate Treg cells in individuals with systemic lupus erythematosus supporting the use of CD4(+)CD25(+)CD127(low/-) to identify human Treg cells.
Inflammation 07/2012; · 1.75 Impact Factor
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ABSTRACT: To determine the significance of hepatitis B virus (HBV)-associated antigen deposition in renal tissue from patients with systemic lupus erythematosus (SLE).
The medical records of 166 inpatients with lupus nephritis and 384 controls without SLE were analyzed retrospectively. Patients with SLE were classified as positive or negative depending on whether HBV-associated antigen deposition was detected in renal biopsies.
HBV-associated antigen deposition was mainly detected in renal tissue from patients with SLE (50.6%), primary renal glomerular disease (20.8%), and allergic purpura (21.7%). It was not detected in renal tissue from patients with diabetic nephropathy, hypertensive nephrosclerosis, thin basement membrane nephropathy, or Alport syndrome. Hepatitis B surface antigen and core antigen were deposited in the mesangial region and vascular loops. The positive group had a significantly higher frequency of IgG, IgA, and IgM deposition than the negative group (53.6% vs 30.5%; p < 0.01). There was no significant difference in the types of lupus nephritis observed between the 2 groups.
There was a high prevalence of HBV-associated antigen deposition in renal tissue of patients with SLE by indirect immunofluorescence, which may result mainly from the cross-reactivity with deposited immunoglobulins.
The Journal of Rheumatology 03/2012; 39(5):974-8. · 3.69 Impact Factor
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ABSTRACT: Systemic lupus erythematosus (SLE) is a systemic autoimmune disease affecting many organs. Many autoantibodies have been associated with the disease, but either in low specificity or low sensitivity of detection. In an aim to screen for better autoantibodies, we profiled the autoantibody repertoire in sera from 30 SLE patients versus 30 healthy controls using a protein microarray containing 5011 non-redundant human proteins, and identified four candidates. We then selected CLIC2 for further verification by ELISA in an extended cohort including 110 SLE, 121 non-AD, 118 RA, 117 SSc, and 105 pSS patients. The positive rate of anti-CLIC2 was 28.18% in SLE patients, significantly higher than those in non-AD, RA, and SSc patients. The presence of anti-CLIC2 in SLE had positive correlation with disease activity in terms of SLEDAI score and several indexes (p<0.05).
Biochemical and Biophysical Research Communications 02/2012; 418(2):241-6. · 2.48 Impact Factor
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ABSTRACT: Auto-reactive B lymphocytes and its abnormal CD40 signaling play important roles in the pathogenesis of systemic lupus erythematosus (SLE). In this study, we analyzed CD40 expression and CD40/CD154 induced activation of NF-κB signaling pathway in B cells from SLE patients. B cells from healthy volunteers and tonsilar B cells from chronic tonsillitis were used as negative and positive controls. Results showed CD40-induced NF-κB signaling was constitutively activated in B cells from active lupus patients, including decreased CD40 in raft portion, increased phosphorylation and degradation of IκBα, phosphorylation of P65, as well as increased nuclear translocation of P65, P50, c-Rel, which could be blocked by anti-CD154. CD154 stimulation could induce further phosphorylation and degradation of IκBα, as well as phosphorylation of P65 and nuclear translocation of P65. In addition, CD40-induced kinase activities in B cells from lupus patients mimicked that of tonsil B cells, in that IKKα/β were more activated compared to normal B cells. CD40-induced NF-κB activity was blocked by both IκB phosphorylation and proteosome degradation inhibitors in both lupus and normal B cells. All together, our findings revealed that canonical NF-κB signaling is constitutively activated in active lupus and is mediated by CD154/CD40. CD40 induced NF-κB activation is different in human lupus B lymphocytes compared with normal B cells.
PLoS ONE 01/2012; 7(8):e41644. · 4.09 Impact Factor
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ABSTRACT: We aimed to compare bone-marrow-derived mesenchymal stem cells (BMMSCs) between systemic lupus erythematosus (SLE) and normal controls by means of cDNA microarray, immunohistochemistry, immunofluorescence, and immunoblotting. Our results showed there were a total of 1, 905 genes which were differentially expressed by BMMSCs derived from SLE patients, of which, 652 genes were upregulated and 1, 253 were downregulated. Gene ontology (GO) analysis showed that the majority of these genes were related to cell cycle and protein binding. Pathway analysis exhibited that differentially regulated signal pathways involved actin cytoskeleton, focal adhesion, tight junction, and TGF-β pathway. The high protein level of BMP-5 and low expression of Id-1 indicated that there might be dysregulation in BMP/TGF-β signaling pathway. The expression of Id-1 in SLE BMMSCs was reversely correlated with serum TNF-α levels. The protein level of cyclin E decreased in the cell cycling regulation pathway. Moreover, the MAPK signaling pathway was activated in BMMSCs from SLE patients via phosphorylation of ERK1/2 and SAPK/JNK. The actin distribution pattern of BMMSCs from SLE patients was also found disordered. Our results suggested that there were distinguished differences of BMMSCs between SLE patients and normal controls.
Clinical and Developmental Immunology 01/2012; 2012:826182. · 1.84 Impact Factor
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Hua Chen,
Wenjie Zheng,
Jinmei Su,
Dong Xu,
Qian Wang,
Xiaomei Leng,
Wen Zhang,
Mengtao Li,
Fulin Tang,
Xuan Zhang, Xiaofeng Zeng,
Yan Zhao,
Fengchun Zhang
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ABSTRACT: To evaluate the safety and efficacy of low-dose rituximab therapy for refractory thrombocytopenia in patients with SLE.
Ten adult SLE patients with severe refractory thrombocytopenia (mean platelet count 10.4 × 10(9)/l) were enrolled in this prospective pilot study. All patients had failed traditional high-dose CSs and immunosuppressants including methylprednisolone pulse therapy. Patients were scheduled to receive i.v. rituximab at a dose of 100 mg once weekly for 4 weeks. Previous dose of CSs were gradually tapered, and immunosuppressants were withdrawn. Patients were followed at Weeks 4, 12, 24 and 36.
All patients completed four courses of low-dose rituximab infusion. At Week 4, two (20%) patients achieved complete responses (CRs, platelet count >100 × 10(9)/l). The CR rate increased to 60% (six patients) at Week 12, was maintained at Week 24 and began to drop at Week 36 (four patients, 40%). Overall response (OR, platelet count >50 × 10(9)/l) was achieved in 5/10, 6/10, 7/10 and 5/10 patients at Weeks 4, 12, 24 and 36, respectively. Peripheral CD19(+) B cells were depleted (<5 × 10(6)/l) in all patients at Week 4, and gradually increased at Weeks 24 and 36. Serum C3, IgG, IgA and IgM levels did not change significantly (P < 0.05). Infusion reaction was observed in two patients. One patient developed pulmonary thrombosis at Week 14 and active tuberculosis at Week 25.
Low-dose rituximab therapy is effective in treating severe thrombocytopenia in SLE patients who do not respond to vigorous glucocorticoid plus immunosuppressants, and in most cases is safe.
Rheumatology (Oxford, England) 05/2011; 50(9):1640-4. · 4.24 Impact Factor
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ABSTRACT: The impact of pregnancy on lupus activity has been controversial especially in Chinese women. Research looking at predictive factors in this population are sparse. The aim of this study was therefore twofold: to determine the frequencies of abnormal pregnancy outcomes in a Chinese cohort and to identify clinical and laboratory factors predicting adverse fetal and maternal outcomes in Chinese women with systemic lupus erythematosus.
Data of 111 pregnancies of 105 systemic lupus erythematosus (SLE) patients from January 1990 to December 2008 in Peking Union Medical College Hospital in Beijing were analyzed retrospectively. Univariate analysis using chi-square test and logistic regression was used to assess the predictive value of each variable on binary outcomes. Lupus activity was based on SLE Disease Activity Index (SLEDAI) criteria.
There were 23 elective, 2 spontaneous abortions, and 5 stillbirths, with 81 pregnancies resulting in live births including two multiple gestations. Three neonatal deaths were reported. Fetal loss rate including neonatal death was 11.1%. Fetal loss in active SLE group (17.0%) was significantly higher than those in inactive group (2.0%) (P = 0.047). The incidence of premature birth in active SLE group was 25/47 (53.2%), which is significantly higher than those in inactive group (3/34, 8.8%) (P < 0.001). Small for gestational age (SGA) was more common in active SLE group with incidence of 40.0% compared to 5.6% in inactive group (P < 0.001). Five fetal malformations were recorded (6.0%), including three fetal heart malformations (one complete heart block, one tetralogy of Fallot, and one atrial septal defect) and two multiple fetal malformations, which were significantly higher than general population. Among 25 pregnancies that were in active stage at conception, 14 (56%) deteriorated during pregnancy. Of the 68 pregnancies that were stable at conception, 26 (38%) flared during pregnancy or postpartum. Preeclampsia/eclampsia (OR = 14.83, 95% CI: 3.83-57.41) and thrombocytopenia (OR = 4.43, 95% CI: 1.12-17.60) were significant predictors of fetal loss; preeclampsia/eclampsia (OR = 8.04, 95% CI: 2.00-32.34) and active SLE (OR = 19.90, 95% CI: 2.38-166.27) were significantly associated with preterm birth; preeclampsia/eclampsia (OR = 8.92, 95% CI: 2.25-35.44) and thrombocytopenia (OR = 4.03, 95% CI: 1.24-17.25) were also significant predictors of maternal SLE flare-up.
In general, lupus in pregnancy in the Chinese population is generally similar to other cohorts. Pregnancies can be successful in most women with SLE. However, an increase in SLE activity can occur in a significant number of patients, even those who are well controlled. Adverse fetal outcome including fetal loss, preterm birth, and SGA increases significantly with SLE flares during pregnancy with preeclampsia/eclampsia, thrombocytopenia, and active SLE serving independent predictors of adverse fetal and maternal outcome. Fetal echo should not just for heart block but for structural abnromalities as the structural malformation rate was significantly higher than general population, especially congenital heart disease.
The journal of maternal-fetal & neonatal medicine: the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians 04/2011; 25(3):261-6. · 1.36 Impact Factor
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ABSTRACT: Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease with complex genetic inheritance. Genome-wide association studies have identified SLE susceptibility variations at the IRF7/KIAA1542 locus and with STAT4 gene in European populations. We decided to investigate the association of single-nucleotide polymorphisms (SNPs) in the IRF7/KIAA1542 region (rs4963128, rs2246614, and rs702966) and in STAT4 (rs7574865 and rs7582694) with SLE disease in a Northern Han Chinese population of 748 patients and 750 healthy controls. Our study indicated a strong association between rs7574865 (odds ratio = 0.68; 95% confidence interval 0.59-0.79; p = 1.57 × 10(-6)) and SLE and between rs7574865 and the production of anti-Sm antibodies. Additionally, rs4963128 and rs2246614 were correlated with a variety of clinical subphenotypes, such as lupus nephritis, arthritis, and the production of anti-SSA/B autoantibodies, despite a lack of significant association between these two SNPs and SLE disease susceptibility in general.
Human immunology 03/2011; 72(3):249-55. · 2.55 Impact Factor
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ABSTRACT: Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease with complex genetic inheritance. Genetic association of signal transducer and activator of transcription 4 (STAT4) with SLE susceptibility has been convincingly established in multiple populations including Asians, whereas studies of genetic relations between STAT4 polymorphisms and subphenotypes of SLE were rarely conducted. In this study, we selected Chinese female population and investigated genetic association between a polymorphism of STAT4 gene (rs7582694) and SLE. Furthermore, genetic association tests based on different subsets classified by 11 clinical manifestations were also performed. A total of 675 SLE female patients and 678 healthy controls were enrolled into this study, and SNP genotyping was performed using Sequenom's MassArray system (Sequenom iPLEX assay). Our study showed strong evidence for genetic predisposition of rs7582694 to SLE (X ( 2 ) = 23.7, OR = 0.68, 95% CI: 0.58-0.79, P = 1.13 × 10(-6)), while no association was observed between rs7582694 and any clinical presentations. The results of our study demonstrated that STAT4 rs7582694 SNP was significantly associated with SLE, and these results were in accordance with previous studies.
Rheumatology International 01/2011; 32(5):1251-5. · 1.88 Impact Factor
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ABSTRACT: The objective of this study is to evaluate the clinical features and prognosis of adult-onset Still's disease (AOSD). One hundred and four AOSD patients who were analyzed retrospectively were enrolled in this study. Medical charts were systematically reviewed for: demographic data, clinical features, laboratory findings, treatments, and outcomes. The major clinical features were: spiking fever 100%, evanescent maculopapular rash 95%, polyarthralgia 90%, sore throat 78%, lymphadenopathy 66%, hepatosplenomegaly 57%, hydrohymenitis 30%, neutrophilia 98%, liver disfunction 62%, increased erythrocyte sedimentation rate (ESR) 96%, and hyperferritinaemia 99%. Reactive hyperplasia was shown in all patients who underwent lymph node biopsy. Ninety-five percent and 63% of the patients were treated with glucocorticoid and immune suppressant, respectively. Those with prednisone or its equivalent dosage of > or =0.8 mg/kg/d achieved quicker remission and less relapse. Persistent fever, evanescent rash, arthritis, and sore throat were the most prevalent symptoms in patients with AOSD, with laboratory findings of leukocytosis, elevated liver enzymes, elevated ESR and serum ferritin. Glucocorticoid and immune suppressive drugs are effective for AOSD; however, the relapsing rate is relatively high. High levels of white blood cells, serum ferritin and ESR, as well as glucocorticoid dosage were related to relapse.
Clinical Rheumatology 09/2010; 29(9):1015-9. · 2.00 Impact Factor
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ABSTRACT: To determine the safety and efficacy of allogeneic mesenchymal stem cell transplantation (MSCT) in refractory systemic lupus erythematosus (SLE).
A total of 15 patients with persistently active SLE underwent MSCT. Outcome was evaluated by changes in the SLE disease activity index (SLEDAI), serological features (anti-nuclear antibodies and anti-double-stranded DNA (anti-dsDNA)), renal function and percentage of peripheral blood regulatory T cells.
From 11 March 2007 to 4 November 2008, 15 patients with persistently active SLE were enrolled and underwent MSCT. The mean follow-up period was 17.2+/-9.5 months. A total of 13 patients have been followed for more than 12 months. All patients clinically improved following treatment with mesenchymal stem cells with a marked decrease in the SLEDAI score and 24 h proteinuria. At 12-month follow-up, SLEDAI scores decreased from 12.2+/-3.3 to 3.2+/-2.8 and proteinuria decreased from 2505.0+/-1323.9 to 858.0+/-800.7 mg/24 h (all p<0.05, by paired t test, n=12). At 1-year follow-up in 13 patients, 2 had a relapse of proteinuria, while the other 11 continue to have decreased disease activity on minimal treatment. Anti-dsDNA levels decreased. Improvement in glomerular filtration rate was noted in two patients in which formal testing was performed. Non-renal-related manifestations also improved significantly. No serious adverse events were reported.
Allogeneic MSCT in patients with refractory lupus resulted in amelioration of disease activity, improvement in serological markers and stabilisation of renal function. MSCT appears beneficial in treatment of patients with SLE refractory to conventional treatment options.
Annals of the rheumatic diseases 08/2010; 69(8):1423-9. · 8.11 Impact Factor
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Lingyun Sun,
Dandan Wang,
Jun Liang,
Huayong Zhang,
Xuebing Feng,
Hong Wang,
Bingzhu Hua,
Bujun Liu,
Shengqin Ye,
Xiang Hu,
Wenrong Xu, Xiaofeng Zeng,
Yayi Hou,
Gary S Gilkeson,
Richard M Silver,
Liwei Lu,
Songtao Shi
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ABSTRACT: Umbilical cord (UC)-derived mesenchymal stem cells (MSCs) have shown marked therapeutic effects in a number of diseases in animal studies, based on their potential for self-renewal and differentiation. No data are available on the effectiveness of UC MSC transplantation (MSCT) in human autoimmune disease. This study was undertaken to assess the efficacy and safety of allogeneic UC MSCT in patients with severe and treatment-refractory systemic lupus erythematosus (SLE).
We conducted a single-arm trial that involved 16 SLE patients whose disease was refractory to standard treatment or who had life-threatening visceral involvement. All of the patients gave consent and underwent UC MSCT. Clinical changes were evaluated before and after transplantation using the SLE Disease Activity Index (SLEDAI), measurement of serum antinuclear antibody (ANA), anti-double-stranded DNA (anti-dsDNA) antibody, serum complement C3 and C4, and albumin levels, and assessment of and renal function. Evaluation of potential mechanisms of MSCT effects focused on the percentage of peripheral blood Treg cells and serum levels of cytokines.
From April 2007 to July 2009, a total of 16 patients with active SLE were enrolled and underwent UC MSCT. The median followup time after MSCT was 8.25 months (range 3-28 months). Significant improvements in the SLEDAI score, levels of serum ANA, anti-dsDNA antibody, serum albumin, and complement C3, and renal function were observed. Clinical remission was accompanied by an increase in peripheral Treg cells and a re-established balance between Th1- and Th2-related cytokines. Significant reduction in disease activity was achieved in all patients, and there has been no recurrence to date and no treatment-related deaths.
Our findings indicate that UC MSCT results in amelioration of disease activity, serologic changes, and stabilization of proinflammatory cytokines. These data provide a foundation for conducting a randomized controlled trial of this new therapy for severe and treatment-refractory SLE.
Arthritis & Rheumatism 08/2010; 62(8):2467-75. · 7.87 Impact Factor
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ABSTRACT: Bone-marrow-derived mesenchymal stem cells (BMMSC) are multipotent non-hematopoietic progenitor cells that are being explored as a promising new treatment for tissue regeneration. Although their immunomodulatory properties are not yet completely understood, their low immunogenic potential together with their effects on immune response make them a promising therapeutic tool for severe refractory autoimmune diseases including systemic lupus erythematosus (SLE).
Our aim is to discuss recent progress in understanding the role of malfunctioning BMMSC in etiopathogenesis of SLE and to explore allogenic BMMSC transplantation as a potential therapy for SLE.
Recent evidence suggests that the functions of BMMSC are disrupted in SLE pathology. This malfunction may result as a corollary of the disease, or may play a more fundamental role in its etiopathogenesis. We provide a brief characterization of BMMSC immunomodulatory effects, and describe our current understanding of the mechanisms by which it plays a part in treating SLE. We also present our clinical trial using allogenic BMMSC in this context.
Allogenic BMMSC appear to be a safe therapeutic option for treatment-resistant SLE as illustrated in our clinical trial.
Expert opinion on biological therapy 03/2010; 10(5):701-9. · 3.22 Impact Factor
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ABSTRACT: Recent evidence indicates that artesunate has immunomodulatory properties that might be useful for treating autoimmune disease. In this study, we conducted a pilot study and explored the effect and mechanism of artesunate on the treatment of systemic lupus erythematosus using an MRL/lpr murine model. MRL/lpr mice were divided into control, cyclophosphamide (CTX) and artesunate treatment groups. Blood was collected to measure serum levels of creatinine, antinuclear antibody (ANA) and anti-double-stranded DNA (anti-dsDNA) antibody. Twenty-four-hour urine was collected to measure levels of proteinuria. The concentration of monocyte chemotactic protein-1 (MCP-1) in serum and urine was measured. The expression of MCP-1 in kidney was detected by Western blot and immunohistochemistry assay, respectively. The expression of B cell activating factor (BAFF) in spleen was determined by real time-PCR and immunoblotting. We found that artesunate significantly increased the survival rate, body weight and blood leukocyte counts, and reduced the serum levels of ANA and anti-dsDNA antibody titer, 24 h urinary protein, and serum creatinine. Our results indicated that artesunate could decrease MCP-1, major pro-inflammation cytokine, in serum, urine and kidney. We also found that the level of BAFF, the major B cell activation factor, was decreased in artesunate treated MRL/lpr mice. Its efficacy was comparable with that of CTX in this study. Taken together, we have demonstrated that artesunate can inhibit the progression of disease and reverse the pathologic lesion of lupus nephritis.
Cellular & molecular immunology 12/2009; 6(6):461-7. · 2.99 Impact Factor
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ABSTRACT: A 9-year-old girl with a history of xerostomia and recurrent bilateral parotid gland enlargement presented with purpura of the lower limbs and exertional dyspnea. She had hyperglobulinemia, positive ANA, SSA, and SSB and an abnormal Shirmer test leading to a diagnosis of primary Sjögren syndrome. Cardiologic and imaging investigations revealed severe isolated pulmonary hypertension and ruled out pulmonary fibrosis. Prednisolone and cyclophosphamide, together with anticoagulant and vasodilatory drugs therapy, induced a significant improvement of exertional dyspnea and lowered pulmonary artery pressure. This case and reports from the literature suggest that immune mechanisms, not just vasospasm, can be factors in some pulmonary hypertension.
JCR Journal of Clinical Rheumatology 11/2007; 13(5):276-7. · 1.36 Impact Factor
