[Show abstract][Hide abstract] ABSTRACT: To evaluate the psychometric properties and clinical utility of Chinese Multidimensional Health Assessment Questionnaire (MDHAQ-C) in patients with rheumatoid arthritis (RA) in China.
PLoS ONE 01/2014; 9(5):e97952. · 3.73 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To investigate the construct and criterion validity of the Euro Qol-5D (EQ-5D), which allows quality-adjusted life-years to be calculated, in patients with systemic lupus erythematosus (SLE).
PLoS ONE 01/2014; 9(6):e98883. · 3.73 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To establish an improved substrate for an indirect immunofluorescence test (IIF) to detect anti-Sm antibody.
Full-length Smith protein D1(Sm-D1) complementary DNA was obtained from human larynx carcinoma cell line HEp-2 by reverse transcription - polymerase chain reaction (RT-PCR) and cloned into the mammalian expression vector pEGFP-C1. The recombinant plasmid pEGFP-Sm-D1 was transfected into HEp-2 cells. The expression, localization and antigenicity of fusion proteins of green fluorescent protein (GFP) in transfected cells were confirmed by means of immunoblotting (IBT), confocal fluorescence microscopy and IIF analysis. Transfected HEp-2 cells were analyzed with reference serum and compared with untransfected HEp-2 cells by IIF.
Stable expression of the Sm-D1-GFP was maintained for more than ten generations. This Sm-D1-GFP showed the antigenicity of Sm-D1 with a characteristic phenotype in IIF.Six of 12 serum specimens from systemic lupus erythematosus contained both 29/28 and 13.5 kDa proteins and showed characteristic immunofluorescent patterns. The same phenomenon appeared in 3/6 serum samples which contained 29/28 kDa proteins only. Sera from 10 healthy donors did not react with HEp-Sm-D1 or HEp-2 at 1:80 attenuant degrees. No alteration in expression, localization and morphology was observed when HEp-Sm-D1 or HEp-2 interacted with the reference sera which could react with Ro/SSA, La/SSB, β2GP1, centromere, histone, and Scl-70 antibodies in routine IIF tests.
As a new kind of substrate of IIF, HEp-Sm-D1 can be used to detect anti-Sm antibodies. Transfected HEp-2 cells keep the immunofluorescent property of HEp-2 cells in immunofluorescence anti-nuclear antibody (IFANA) test and could potentially be used as substrate for routine IFANA detection.
International Journal of Rheumatic Diseases 06/2013; 16(3):303-9. · 1.65 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: INTRODUCTION: Adult-onset still's disease (AOSD) is a rare systemic inflammatory disorder in which abnormalities in inflammatory cytokines production appear to play a pathophysiological role. Our previous work has reported increased expression of macrophage migration inhibitory factor (MIF) and revealed its correlation with disease severity and activity in AOSD. A -173 G/C single nucleotide polymorphism (SNP)(rs755622) and a -794 CATT5-8 repeat (rs5844572) in the MIF promoter have been reported. In this study, we sought to explore the relationship between functional MIF promoter polymorphisms and MIF expression in AOSD. METHODS: 100 patients and 200 controls were recruited in the study. A polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay was utilized to analyze the -173 G/C SNP (rs755622) and PCR-based size discrimination assay was applied to detect the -794 CATT5-8 repeat (rs5844572) in the MIF promoter. Plasma MIF levels were measured by ELISA. MIF mRNA levels were quantified by real-time reverse transcription (RT)-PCR. Bisulfate genomic sequencing was employed to evaluate DNA methylation status within the MIF promoter. RESULTS: We identified that the frequencies of MIF -794 CATT5 (P=0.001) allele and the expression of MIF (P<0.001) were increased in patients compared to healthy controls. Plasma levels of MIF in patients with CC genotype were higher than those of patients with GC or GG genotypes(P=0.05). In patients with established AOSD, a higher frequency of -794 CATT7 containing MIF genotypes was observed in those with liver dysfunction (P=0.009). Haplotype analysis revealed a higher representation of the MIF haplotype defined by -173*C / -794 CATT5 (C5) in AOSD patients (P=0.001). CONCLUSION: Functional promoter polymorphisms in the MIF gene influence plasma MIF levels in AOSD and may contribute to disease susceptibility or clinical presentation of AOSD.
Arthritis research & therapy 05/2013; 15(3):R65. · 4.27 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To adapt and assess the validity and reliability of LupusQoL for use in Chinese patients with systemic lupus erythematosus (SLE).
Debriefing interviews of subjects with SLE guided the language modifications of the tool. The process of adaptation proceeded according to the guideline and pre-testing results of LupusQoL-China. 220 SLE patients completed LupusQoL-China and a generic preference-based measurement of health EuroQoL scale (EQ-5D), and 20 patients repeated them after 2 weeks. Internal consistency (ICR) and test-retest (TRT) reliability, convergent and discriminant validity were examined. Factor analysis and Rasch analysis were performed.
The mean (SD) age of the 208 subjects with SLE was 33.93 (±9.19) years. ICR and TRT of the eight domains ranged from 0.811 to 0.965 and 0.836 to 0.974, respectively. The LupusQoL-China domains demonstrated substantial evidence of construct validity when compared with equivalent domains on the EQ-5D (physical health and usual activities r = -0.63, pain and pain/discomfort r = -0.778, emotional health and anxiety/depression r = -0.761, planning and usual activities r = -0.560). Most LupusQoL-China domains could discriminate patients with varied disease activities and end-organ damage (according to SELENA-SLEDAI and SLICC-DI). The principal component analysis revealed six factors, and confirmatory factor analysis result of which is similar to eight factors model.
These results provide evidence that the LupusQoL-China is valid as a disease-specific HRQoL assessment tool for Chinese patients with SLE.
PLoS ONE 01/2013; 8(5):e63795. · 3.73 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Glucocorticoid (GC) therapy remains important in improving the prognosis of patients with systemic lupus erythematosus (SLE). However, some patients do not achieve an effective response with GC treatment, creating an obstacle to the remission of SLE. Identification of the underlying mechanisms responsible for steroid resistance can be significant. Macrophage migration inhibitory factor (MIF) arouses our interest because of its reciprocal relationship with GCs. In the present study, we investigated for the first time whether MIF correlated with steroid resistance in SLE and explored potential mechanisms of action.
Sixty-two patients with SLE (40 steroid sensitive and 22 steroid resistant) and 21 normal controls were recruited. Serum levels of MIF were measured by ELISA. Cytosolic MIF and IκB expression in peripheral blood mononuclear cells (PBMCs) were determined by western blotting. The electrophoretic mobility shift assay was assessed by NF-κB in nuclear aliquots. Gene silencing was applied to reduce expression of MIF in PBMCs in steroid-resistant patients. PBMCs obtained from steroid-sensitive patients were treated with recombinant human MIF of different concentrations.
MIF levels in serum and PBMCs were higher in steroid-resistant patients compared with steroid-sensitive patients and controls. In contrast to the steroid-sensitive group, NF-κB levels were significantly higher and IκB levels lower in steroid-resistant patients. After MIF gene silencing, IκB levels in cells from steroid-resistant patients were increased. In steroid-sensitive patients, a decrease in IκB levels and an increase in NF-κB expression from baseline were detected in PBMCs treated with a higher concentration of recombinant human MIF. Treatment with recombinant human MIF did not regulate expression of IκB and NF-κB in PBMCs from patients treated with an anti-MIF monoclonal antibody.
Our results indicated that MIF may play a role in the formation of steroid resistance in SLE by affecting the NF-κB/IκB signaling cascade. As a regulator of glucocorticoid sensitivity, MIF may be a potential target for steroid sparing.
Arthritis research & therapy 05/2012; 14(3):R103. · 4.27 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To analyse the cost-effectiveness of traditional disease-modifying anti-rheumatic drugs (tDMARDs) compared to biological therapies from the perspective of Chinese society.
A mathematical model was developed by incorporating the clinical trial data and Chinese unit costs and treatment sequences from a lifetime perspective. Hypothetical cohorts with moderate to severe RA were simulated. The primary outcome measure-quality-adjusted life years (QALYs)-was derived from disease severity (HAQ scores). Primary analysis included drug costs, monitoring costs, and other costs. Probabilistic and one-way sensitivity analyses were performed. Treatment sequences that included TNF antagonists and rituximab produced a greater number of QALYs than tDMARDs alone or TNF antagonists plus DMARDs. In comparison with tDMARDs, the incremental cost-effectiveness ratios (ICERs) for etanercept, infliximab, and adalimumab without rituximab were $77,357.7, $26,562.4 and $57,838.4 per QALY and $66,422.9, $28,780.6 and $50,937.6 per QALY, for etanercept, infliximab, and adalimumab with rituximab. No biotherapy was cost-effective under the willingness to pay threshold when the threshold was 3 times the per capita GDP of China. When 3 times the per capita GDP of Shanghai used as the threshold, infliximab and rituximab could yield nearly 90% cost-effective simulations in probabilistic sensitivity analysis.
tDMARD was the most cost-effective option in the Chinese healthcare setting. In some relatively developed regions in China, infliximab and rituximab may be a favorable cost-effective alternative for moderate to severe RA.
PLoS ONE 01/2012; 7(10):e47373. · 3.73 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To assess the efficacy and safety of T-614 versus methotrexate (MTX) in patients with active rheumatoid arthritis (RA).
In this multicenter, double-blind trial, 489 patients randomly received either T-614 25 mg/day for the first 4 weeks and 50 mg/day for the subsequent 20 weeks (group 1, n = 163), T-614 50 mg/day for 24 weeks (group 2, n = 163), or MTX 10 mg/week for the first 4 weeks and 15 mg/week for the subsequent 20 weeks (n = 163). Clinical and laboratory parameters were analyzed at baseline and at 4, 10, 17, and 24 weeks.
After 24 weeks of treatment, the American College of Rheumatology 20% improvement criteria response rate for patients in T-614 group 2 (63.8%) was not statistically significantly different from that for patients receiving MTX treatment (62.0%), and was superior to that for patients in T-614 group 1 (50.9%). The result of the noninferiority analysis indicated that the efficacy of T-614 (50 mg/day) was not lower than that of MTX by <10%. Rheumatoid factor and IgA, IgG, and IgM demonstrated a statistically significant decrease in all groups. Frequently reported adverse events included hematologic disorder, skin reactions, gastrointestinal symptoms, and transient liver enzyme elevations in the T-614 therapy groups. Side effects in the T-614 groups were generally fewer and milder than in the MTX group, except for skin reactions. There were no prominent cardiovascular adverse events and gastrointestinal ulcers found in the T-614 groups.
Results indicate that T-614 therapy 50 mg/day is effective and well tolerated, and represents a new option for the treatment of patients with active RA.
[Show abstract][Hide abstract] ABSTRACT: To evaluate the prevalence of atherosclerosis in Chinese premenopausal women with systemic lupus erythematosus (SLE) and study possible associations between traditional and nontraditional risk factors with premature atherosclerosis.
We evaluated 111 premenopausal women with SLE and 40 healthy controls without clinical cardiovascular disease. B-mode ultrasound was used to measure carotid plaque and intima-media wall thickness (IMT). The frequency of risk factors for atherosclerosis in patients and controls was compared, and the relationship between the patients' clinical characteristics and carotid plaque was examined. At the same time, we used B-mode ultrasound to measure flow-mediated dilation (FMD) and nitroglycerin-mediated dilation (NMD) in the brachial artery to assess for difference in endothelial function between SLE patients and controls.
Carotid plaque was more frequent in patients with lupus (16 of 111 patients) than in control subjects (0 of 40 subjects) (P = 0.007). The mean IMT was significantly higher in patients than in controls. Compared with controls, SLE patients were found to have a significantly higher prevalence of hypertension (P = 0.001), hypercholesterolemia (P = 0.022), and hypertriglyceridemia (P < 0.001). As compared with patients without plaque, patients with plaque were significantly older, had longer disease duration, higher body mass index, raised blood pressure, shorter prothrombin time, raised C-reactive protein, higher Systemic Lupus International Collaborating Clinics damage index score, higher cumulative prednisone dose, used less hydroxychloroquine, had higher mean IMT, lower FMD, and NMD. In logistic regression analysis, older age, higher body mass index, and higher Systemic Lupus International Collaborating Clinics damage index score were independently related to the presence of plaque. Using multiple regression analysis, we found SLE (P = 0.003) to be significantly associated with impaired FMD.
In our Chinese SLE group, patients presented a higher prevalence of carotid atherosclerosis plaque than healthy controls. SLE patients have significant endothelial dysfunction. We found that risk factors identified in other SLE populations were associated with atherosclerosis in our Chinese group.
Journal of clinical rheumatology: practical reports on rheumatic & musculoskeletal diseases 04/2009; 15(3):111-6. · 1.19 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To review the current status of lupus registries, highlight the importance and evolution of registries in clinical lupus research, discuss substantial advances in the understanding of lupus through the use of registries, and discuss the future role of registries in terms of opportunities and challenges.
The literature reviewed originated from the PubMed database and was limited to adult disease in articles published before June 01, 2008. Keywords used in the PubMed search included the following terms: systemic lupus erythematosus, registry, cohort, and database. All articles were sorted and analyzed according to a template devised by the authors describing the different types of registries.
The most important features of a lupus registry are that they contain a large number of subjects and reflect a relatively real world environment for lupus patients. Data obtained from the lupus registries are essential for planning, designing, and conducting clinical lupus studies, especially those difficult, inappropriate, or even unethical to study in randomized controlled trials. Up to now, some well-conducted registries have received recognition for their contributions to lupus research through their focus on different goals: epidemiology, genetics, ethnic diversity, clinical features, or outcomes. Although they have evolved in design and study emphasis steadily, there are still many issues left to resolve. Apart from the development and future direction of the lupus registry, attention needs to be applied to normalizing the ethical and legal rules involving a lupus registry.
Lupus registries have demonstrated high standards and achieved much success through decades of effort, but they are still in an active state of evolution as they address more questions with greater clarity and sophistication.
Seminars in arthritis and rheumatism 12/2008; 39(4):224-45. · 4.72 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This study investigated the levels of macrophage migration inhibitory factor (MIF) in adult-onset Still's disease (AOSD) and explored the role of this pro-inflammatory cytokine in the systemic inflammation of AOSD.
Serum MIF levels were measured by ELISA in patients with AOSD and controls. Intracellular MIF production by peripheral blood leukocytes was detected by three-color flow cytometry.
Serum MIF levels were significantly increased in patients with AOSD. Serum MIF levels were significantly higher in AOSD patients with sore throat, myalgias, splenomegaly, or pleuritis, and were closely correlated with clinical disease severity and activity. Examined by flow cytometry, the intracellular MIF levels in monocytes and T-lymphocytes from AOSD patients were significantly higher than those from healthy subjects.
These data represent the first demonstration of increased MIF expression in AOSD, and suggest that MIF may be an important marker for disease evaluation and monitoring.