Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 32
Filtrar
1.
Rheumatol Ther ; 2021 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-34806155

RESUMO

INTRODUCTION: This phase III trial (NCT04178850) evaluated the efficacy, safety, and immunogenicity of GB242, an infliximab biosimilar, vs. infliximab (Remicade®) reference product in patients with moderate-to-severe active rheumatoid arthritis (RA) combination with methotrexate (MTX) therapy. METHODS: Patients were randomized in a 1:1 ratio to receive either GB242 or INF (3 mg/kg). Therapeutic equivalence of clinical response according to the American College of Rheumatology 20% (ACR20) response rate at week 30 was declared if the two-sided 95% CI for the treatment difference was within ± 14%. The comparison of GB242 with INF also included the proportion of patients achieving a week 30 ACR 50 response, ACR70 response, change in Disease Activity Score 28 (DAS28), as well as safety and immunogenicity. RESULTS: A total of 570 subjects were randomized into GB242 (N = 285) or INF (N = 285) and 283 subjects in each group were analyzed. At week 30, the ACR20 was 62.54% for the GB242 group (95% CI 56.62-68.20%) and 56.89% for the INF group (95% CI 50.90-62.74%). The difference between the two groups was 5.65% with a 95% CI of - 2.48 to 13.74. ACR50 response was 37.12% for GB242 and 32.86% for INF at week 30. ACR70 response was 19.79% for GB242 and 16.96% for INF at week 30, respectively. The incidence of treatment-emergent adverse events was comparable (77.4% in GB242 vs. 80.2% in INF) and detection of antidrug antibodies (ADA) to infliximab up to week 30 (60.8% in GB242 vs. 59.4% in INF) was comparable. CONCLUSIONS: GB242 demonstrated equivalent efficacy to INF at week 30. Moreover, GB242 was well tolerated, with a similar immunogenicity and safety profile comparable to INF.

2.
Sci Rep ; 11(1): 18591, 2021 09 20.
Artigo em Inglês | MEDLINE | ID: mdl-34545152

RESUMO

Environmental exposures interact with genetic factors has been thought to influence susceptibility of systemic lupus erythematosus (SLE) development. To evaluate the effects of environmental exposures on SLE, we conducted a population-based cohort study across Jiangsu Province, China, to examine the associations between the living environment including air and water pollution, population density, economic income level, etc. and the prevalence and mortality of hospitalized SLE (h-SLE) patients. A total of 2231 h-SLE patients were retrieved from a longitudinal SLE database collected by the Jiangsu Lupus Collaborative Group from 1999 to 2009. The results showed that: It existed regional differences on the prevalence of h-SLE patients in 96 administrative districts; The distribution of NO2 air concentration monitored by atmospheric remote sensors showed that three of the ultra-high-prevalence districts were located in the concentrated chemical industry emission area; h-SLE patient prevalence was positively correlated with the excessive levels of nitrogen in drinking water; The positive ratio of pericarditis and proteinuria was positively correlated with the prevalence of h-SLE patients and pollution not only induced a high h-SLE patient prevalence but also a higher mortality rate, which might be attributed to NOx pollution in the air and drinking water. In summary, our data suggested that NOx in air and drinking water may be one of the important predispositions of SLE, especially for patients with renal involvement.


Assuntos
Poluição do Ar/efeitos adversos , Água Potável , Exposição Ambiental/efeitos adversos , Lúpus Eritematoso Sistêmico/epidemiologia , Poluição da Água/efeitos adversos , Adulto , China/epidemiologia , Bases de Dados Factuais , Feminino , Humanos , Lúpus Eritematoso Sistêmico/etiologia , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Adulto Jovem
3.
Front Immunol ; 12: 657860, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34276651

RESUMO

The survival of transplant kidneys using deceased donors (DD) is inferior to living donors (LD). In this study, we conducted a whole-transcriptome expression analysis of 24 human kidney biopsies paired at 30 minutes and 3 months post-transplantation using DD and LD. The transcriptome profile was found significantly different between two time points regardless of donor types. There were 446 differentially expressed genes (DEGs) between DD and LD at 30 minutes and 146 DEGs at 3 months, with 25 genes common to both time points. These DEGs reflected donor injury and acute immune responses associated with inflammation and cell death as early as at 30 minutes, which could be a precious window of potential intervention. DEGs at 3 months mainly represented the changes of adaptive immunity, immunosuppressive treatment, remodeling or fibrosis via different networks and signaling pathways. The expression levels of 20 highly DEGs involved in kidney diseases and 10 genes dysregulated at 30 minutes were found correlated with renal function and histology at 12 months, suggesting they could be potential biomarkers. These genes were further validated by quantitative polymerase chain reaction (qPCR) in 24 samples analysed by microarray, as well as in a validation cohort of 33 time point unpaired allograft biopsies. This analysis revealed that SERPINA3, SLPI and CBF were up-regulated at 30 minutes in DD compared to LD, while FTCD and TASPN7 were up-regulated at both time points. At 3 months, SERPINA3 was up-regulated in LD, but down-regulated in DD, with increased VCAN and TIMP1, and decreased FOS, in both donors. Taken together, divergent transcriptomic signatures between DD and LD, and changed by the time post-transplantation, might contribute to different allograft survival of two type kidney donors. Some DEGs including FTCD and TASPN7 could be novel biomarkers not only for timely diagnosis, but also for early precise genetic intervention at donor preservation, implantation and post-transplantation, in particular to effectively improve the quality and survival of DD.


Assuntos
Biomarcadores , Perfilação da Expressão Gênica , Transplante de Rim , Transcriptoma , Adulto , Aloenxertos , Biópsia , Cadáver , Biologia Computacional/métodos , Feminino , Perfilação da Expressão Gênica/métodos , Humanos , Doadores Vivos , Masculino , Pessoa de Meia-Idade , Anotação de Sequência Molecular , Reação em Cadeia da Polimerase em Tempo Real , Reprodutibilidade dos Testes , Transplante Homólogo
4.
Clin Rheumatol ; 40(6): 2221-2231, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33155157

RESUMO

OBJECTIVE: To explore the association between the creatinine clearance rate (Ccr) and the prognosis of patients, and compared with estimated glomerular filtration rate (eGFR). METHODS: We retrospectively collected information of patients with SLE who were first hospitalized between 1999 and 2009 in Jiangsu Province, China, and followed up in 2010 and 2015. Ccr was calculated and dichotomized into normal group (Ccr ≥ 70) and decreasing group (Ccr < 70). The clinical characteristics of the two groups were compared and Cox proportional-hazards regression models were used to calculate hazard ratio (HR) and 95% confidence interval (CI). RESULTS: Among 1990 SLE patients, we observed 437 (22.0%) with decreased Ccr, including 237 cases (11.9%) with mild renal dysfunction, 136 cases (6.8%) with moderate renal dysfunction, and 64 cases (3.2%) with severe renal dysfunction. Compared to normal Ccr, decreasing Ccr had a higher risk for mortality with adjusted HR (95% CI) of 2.21 (1.59-3.06). Dose-response relationships were significantly found between increased mortality of SLE and decreased Ccr (p for trend < 0. 001), as well as eGFR. Positive associations were consistently observed in subgroups, such as systemic lupus disease activity index (SLEDAI) ≥ 15, without comorbidities and abnormal laboratory indexes. Decreasing Ccr was positively associated with mortality from infection and renal failure with HR (95% CI) of 1.80 (1.02-3.19) and 6.84 (3.05-15.36). CONCLUSIONS: A significant association has been observed between decreased Ccr and increased risk for mortality of SLE patients. Early clinical interventions to modulate the Ccr of SLE patients may be beneficial to their survival. Key points • Decreasing creatinine clearance rate (Ccr) was positively associated with an overall mortality of SLE patients, with a dose-response relationship. • Moreover, decreasing Ccr was associated with elevated mortality primarily due to infection and renal failure.


Assuntos
Lúpus Eritematoso Sistêmico , China/epidemiologia , Creatinina , Humanos , Lúpus Eritematoso Sistêmico/diagnóstico , Prognóstico , Estudos Retrospectivos
5.
Clin Rheumatol ; 40(5): 1835-1842, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33128654

RESUMO

OBJECTIVES: The aim of the study is to identify clusters of lymphocyte subsets within treatment-naive systemic lupus erythematosus (SLE) patients and evaluate the potential association of these clusters with disease activities. METHODS: We conducted a cross-sectional study of consecutive 143 treatment-naive SLE patients in the Affiliated Hospital of Nantong University, China. We used hierarchical cluster analysis to classify individuals into clusters based on circulating lymphocyte subset proportions (CD3+CD4+T cell, CD3+CD8+T cell, CD19+B cell, and CD3-CD16 + CD56 NK cell) via R software. Demographic variables, clinical manifestations, laboratory variables, and disease activities were compared among clusters. RESULTS: The SLE patients (median age 35 (26-48) years, 90.9% female) were divided into four clusters. The clustering features were as follows: cluster 1 (B high), cluster 2 (CD4 high), cluster 3 (CD8 high), and cluster 4 (NK high). SLE patients in cluster 1 showed the highest incidence of arthritis (70.6%, 34.2%, 48.3%, and 42.9% in clusters 1, 2, 3, and 4, respectively; P = 0.046), and patients in cluster 3 and cluster 4 showed significantly a higher incidence of nephritis (35.3%, 25.0%, 48.3%, and 61.9% in in clusters 1, 2, 3, and 4, respectively; P = 0.008). Patients in cluster 2 suffered from lower SLE Disease Activity Index (SLEDAI) score (12.1 ± 5.0, 10.3 ± 5.6, 12.2 ± 4.6, and 14.4 ± 7.3 in clusters 1, 2, 3, and 4, respectively; P = 0.046). Regression analysis indicated that, compared with patients in cluster 2, patients in cluster 1 exhibited higher rate of arthritis (OR 4.53, 95% CI 1.38-14.86, P = 0.013), while patients in cluster 3 (OR 2.85, 95%CI 1.15-7.08, P = 0.024) and cluster 4 (OR 4.93, 95%CI 1.76-13.85, P = 0.002) exhibited higher rate of nephritis. CONCLUSION: This study supports the existence of lymphocyte subset clusters with different clinical features in treatment-naive SLE patients, which could help to differentiate between various subsets of SLE. Key Points • Lymphocyte subsets may occur in a pattern of cluster in treatment-naive SLE patients.


Assuntos
Lúpus Eritematoso Sistêmico , Subpopulações de Linfócitos , Adulto , China , Análise por Conglomerados , Estudos Transversais , Feminino , Citometria de Fluxo , Humanos , Lúpus Eritematoso Sistêmico/epidemiologia , Masculino
6.
Rheumatology (Oxford) ; 60(4): 1774-1783, 2021 04 06.
Artigo em Inglês | MEDLINE | ID: mdl-33099642

RESUMO

OBJECTIVE: To evaluate the association and dose-response pattern between antimalarial drugs and overall and cause specific mortality in SLE patients. METHODS: Medical records including information on HCQ/chloroquine (CQ) prescription were extracted from Jiangsu Lupus database. The database was designed to collect data from SLE patients that first-hospitalized during 1999-2009 in Jiangsu province, China, and a follow-up for survival status was performed in 2010 and 2015. Cox and restricted cubic spline models were used to estimate the hazard ratio and 95% CI. RESULTS: We identified 221 deaths among 2446 SLE patients in total. Compared with non-users, decreased overall mortality was associated with either HCQ or CQ users, with adjusted hazard ratio (95% CI) of 0.49 (0.35, 0.67) and 0.49 (0.27, 0.87), respectively. The association between HCQ/CQ and overall mortality was similar across subgroups, such as patients with comorbidities and organ involvements. Interestingly, both the time and the daily dosage of HCQ/CQ use were related to decreased mortality of SLE in a linear dose-response relationship. In cause specific analyses, HCQ/CQ was inversely associated with death from renal insufficiency and other organ (cardiopulmonary, gastrointestinal and haematological) involvements, with adjusted hazard ratio (95% CI) of 0.23 (0.09, 0.55) and 0.25 (0.10, 0.62), respectively, yet it was not significantly associated with mortality from infection and neuropsychiatric involvements. CONCLUSION: Antimalarial drugs were associated with lower risk of SLE mortality, especially renal insufficiency- and other organ involvement-related death. The protective effects for survival might be augmented by adherence and full dosage of these drugs.


Assuntos
Antimaláricos/uso terapêutico , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Lúpus Eritematoso Sistêmico/mortalidade , Adulto , China/epidemiologia , Cloroquina/uso terapêutico , Relação Dose-Resposta a Droga , Feminino , Humanos , Hidroxicloroquina/uso terapêutico , Masculino , Insuficiência Renal/tratamento farmacológico , Insuficiência Renal/mortalidade , Estudos Retrospectivos , Adulto Jovem
8.
Int J Rheum Dis ; 23(11): 1488-1496, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32885598

RESUMO

AIM: To evaluate the clinical and laboratory characteristics, prognostic factors, and outcome of adult rheumatic disease-associated macrophage activation syndrome (MAS). METHOD: A multicenter retrospective study was performed across 4 tertiary hospitals in China between January 1, 2017 to December 31, 2019. RESULTS: There were 61 rheumatic disease patients with MAS enrolled into this retrospective clinical study. Fever and hyperferritinemia are the most frequent clinical feature and laboratory abnormality in MAS patients. Serum ferritin > 6000 ng/mL (odds ratio [OR] = 9.46, 95% CI = 2.53-47.13, P = .005) and hemophagocytosis in bone marrow smear (OR = 11.12, 95%, CI = 3.29-50.65, P = .001) were the 2 most prominent predictive factors indicating MAS occurrence. The 90-day all-cause mortality rate of all rheumatic disease patients with MAS was 22.9% (hazards ratio [HR] = 2.15, 95% CI = 0.81-6.78, P = .05). Platelets < 100 × 109 /L (HR = 3.23, 95% CI = 2.51-4.81, P = .01) and ferritin > 6000ng/mL (HR = 6.12, 95% CI = 2.93-16.27, P = .005) were independent predictors of poor outcome in rheumatic disease-associated MAS. CONCLUSION: Macrophage activation syndrome could be a fatal complication in rheumatic disease. Patients presenting with unexplained fever, serum ferritin > 6000 ng/mL, hepatosplenomegaly and cytopenia at baseline should raise the suspicion of MAS. The presence of serum ferritin > 6000 ng/mL, hepatosplenomegaly and low number of platelets was associated with poor outcome.


Assuntos
Síndrome de Ativação Macrofágica/etiologia , Doenças Reumáticas/complicações , Adulto , Biomarcadores/sangue , China , Feminino , Ferritinas/sangue , Febre/etiologia , Hepatomegalia/etiologia , Humanos , Hiperferritinemia/etiologia , Síndrome de Ativação Macrofágica/diagnóstico , Síndrome de Ativação Macrofágica/mortalidade , Síndrome de Ativação Macrofágica/terapia , Masculino , Prognóstico , Estudos Retrospectivos , Doenças Reumáticas/diagnóstico , Doenças Reumáticas/mortalidade , Doenças Reumáticas/terapia , Medição de Risco , Fatores de Risco , Esplenomegalia/etiologia , Fatores de Tempo , Adulto Jovem
9.
Chin Med J (Engl) ; 132(24): 2899-2904, 2019 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-31855969

RESUMO

BACKGROUND: Clinical outcomes of undifferentiated arthritis (UA) are diverse, and only 40% of patients with UA develop rheumatoid arthritis (RA) after 3 years. Discovering predictive markers at disease onset for further intervention is critical. Therefore, our objective was to analyze the clinical outcomes of UA and ascertain the predictors for RA development. METHODS: We performed a prospective, multi-center study from January 2013 to October 2016 among Chinese patients diagnosed with UA in 22 tertiary-care hospitals. Clinical and serological parameters were obtained at recruitment. Follow-up was undertaken in all patients every 12 weeks for 2 years. Predictive factors of disease progression were identified using multivariate Cox proportional hazards regression. RESULTS: A total of 234 patients were recruited in this study, and 17 (7.3%) patients failed to follow up during the study. Among the 217 patients who completed the study, 83 (38.2%) patients went into remission. UA patients who developed RA had a higher rheumatoid factor (RF)-positivity (42.9% vs. 16.8%, χ = 8.228, P = 0.008), anti-cyclic citrullinated peptide (CCP) antibody-positivity (66.7% vs. 10.7%, χ = 43.897, P < 0.001), and double-positivity rate of RF and anti-CCP antibody (38.1% vs. 4.1%, χ = 32.131, P < 0.001) than those who did not. Anti-CCP antibody but not RF was an independent predictor for RA development (hazard ratio 18.017, 95% confidence interval: 5.803-55.938; P < 0.001). CONCLUSION: As an independent predictor of RA, anti-CCP antibody should be tested at disease onset in all patients with UA.


Assuntos
Artrite Reumatoide/etiologia , Artrite/complicações , Autoanticorpos/sangue , Peptídeos Cíclicos/imunologia , Adulto , Artrite/imunologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Prospectivos
10.
Comput Biol Chem ; 83: 107135, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31751880

RESUMO

Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disorder, and its pathogenesis in males and in cases without accompanying lupus nephritis (LN-) is not fully understood. In this study, we identified 90 (82 up- and 8 downregulated) differentially expressed genes (DEGs) common to female LN-, female LN+ and male LN+ using the GSE65391 and GSE49454 gene expression datasets from Gene Expression Omnibus database (GEO). The protein-protein interaction (PPI) network of 70 DEGs was constructed using STRING and cytoscape, and the Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis showed that the PPI network was significantly enriched in defense response to virus, cytosol, protein binding and measles. Sixteen hubgenes were identified from this PPI network, and Literature Mining Gene Networks molecular of GenCLiP 2.0 showed strong interaction between STAT1, DDX58 and IFIT1. Enrichment analysis of hubgenes in published literature showed the involvement of immune response and interferon-related genes in the pathogenesis of SLE. In addition, the transcription factors STAT1 & 2 and IRF6 & 9 had high Normalized Enrichment Score (NES). The 70 DEGs with PPI network and 16 hubgenes are potential biomarkers of SLE, and can help improve diagnosis and develop individualized therapies.


Assuntos
Biologia Computacional , Lúpus Eritematoso Sistêmico/diagnóstico , Biomarcadores/análise , Feminino , Humanos , Lúpus Eritematoso Sistêmico/imunologia , Masculino , Mapas de Interação de Proteínas
11.
Int J Rheum Dis ; 22(6): 1077-1083, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30968568

RESUMO

OBJECTIVE: The impact of pulmonary infection (PI) on mortality of patients with systemic lupus erythematosus (SLE) has been established. Nevertheless, the effect of risk factors in mortality remains controversial. The objective of this study is to determine the risk factors of short-term mortality among SLE patients with PI. METHOD: The clinical data of 54 SLE patients with 59 episodes of PI who were hospitalized from January 2013 to May 2018 was retrospectively analyzed. Demographic data, clinical features, and outcomes were collected. Logistic regression analysis was carried out to determine the independent predictors of 60-day mortality during hospitalization. We used receiver operating characteristics (ROC) curves to verify the indices as mortality predictors in the study patients. RESULTS: There were a total of 54 patients with 59 episodes of PI. There were 12 deaths during hospitalization. In multivariate analysis, 24-hour urinary protein (24h-PRO) (odds ratio [OR]: 2.713, 95% CI: 1.234-5.965, P = 0.013), peripheral lymphocyte count (OR: 0.066, 95% CI: 0.005-0.887, P = 0.040), and serum complement 3 level (C3) (OR: 0.097, 95% CI: 0.010-0.954, P = 0.045) were associated with mortality among our cohort of SLE patients with PI. ROC curve values were 0.818 for lymphocyte count (95% CI: 0.696-0.907, P = 0.001), 0.894 for 24h-PRO (95% CI: 0.786-0.959, P < 0.001) and 0.825 for C3 (95% CI: 0.704-0.912, P = 0.001). The cut-off value of lymphocytes, 24h-PRO and C3 were 0.53 × 109 /L, 0.92 g and 0.52 g/L, respectively. CONCLUSION: The presence of albuminuria, lymphopenia and low complement C3 levels were independent prognostic predictors of short-term mortality in SLE patients with PI.


Assuntos
Lúpus Eritematoso Sistêmico/mortalidade , Infecções Respiratórias/mortalidade , Adolescente , Adulto , Idoso de 80 Anos ou mais , Albuminúria/mortalidade , Biomarcadores/sangue , Complemento C3/análise , Feminino , Mortalidade Hospitalar , Hospitalização , Humanos , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/terapia , Linfopenia/mortalidade , Masculino , Pessoa de Meia-Idade , Prognóstico , Infecções Respiratórias/diagnóstico , Infecções Respiratórias/terapia , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Adulto Jovem
12.
Braz J Med Biol Res ; 52(4): e8131, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30994732

RESUMO

The leading cause of death in systemic lupus erythematosus (SLE) patients is infection. The objective of this study was to evaluate the distribution of lymphocyte subsets in untreated SLE patients with infections. This was a cross-sectional study. Data from January 2017 to May 2018 were collected. Flow cytometry was used to measure the peripheral lymphocyte subsets including CD3+T cells, CD4+T cells, CD8+T cells, CD19+B cells, CD3-CD16+CD56NK cells, and CD3+CD16+CD56NKT cells in 25 healthy controls and 52 treatment-naive SLE patients, among whom 13 were complicated with infections. Association between the lymphocyte subsets and infections was further analyzed. SLE patients with infections (n=13) showed a significantly higher incidence rate of fever (84.6 vs 28.2%) and serositis (84.6 vs 23.1%), increased level of erythrocyte sedimentation rate (60.5±30.1 vs 37.4±27.1 mm/h), serum C-reactive protein (CRP) (102.7±94.9 vs 9.4±14.9 mg/L), procalcitonin (PCT) (1.07±0.08 vs 0.16±0.13 µg/L), and lower blood hemoglobin (Hb) (93.0±20.5 vs 110.4±16.0 g/L) level compared with non-infection patients (n=39) (all P<0.05). In comparison with non-infectious SLE patients (387.9±261.6/µL), CD4+T cells count decreased significantly in infectious SLE patients (217.8±150.4/µL) (P<0.05), and it was negatively correlated with infection-related indicators including PCT (r=-0.573, P=0.041) and CRP (r=-0.596, P=0.032) levels. Our findings suggested that abnormalities of peripheral lymphocyte subsets were related to the immune disorder of lupus itself, regardless of immunosuppressive treatment. Monitoring lymphocyte subsets, especially CD4+T cells, may be helpful for identifying the presence of infection in SLE patients.


Assuntos
Infecções/sangue , Lúpus Eritematoso Sistêmico/sangue , Subpopulações de Linfócitos , Adulto , Proteína C-Reativa/análise , Estudos de Casos e Controles , Estudos Transversais , Feminino , Citometria de Fluxo , Humanos , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Pró-Calcitonina/sangue , Valores de Referência , Fatores de Risco , Estatísticas não Paramétricas , Adulto Jovem
13.
Inflammation ; 42(1): 255-263, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30209639

RESUMO

Increasing evidence shows miR-155 plays an important role in regulating inflammatory processes in systemic lupus erythematosus (SLE), especially in lupus nephritis (LN). Because the chemokine CXCL13 is implicated in the pathogenesis of LN, here we examined whether miR-155 can modulate the activity of CXCL13 or its receptor CXCR5. We determined the expression of CXCL13 in normal and MRL/lpr mice and found elevated levels of CXCL13 in the kidneys of MRL/lpr mice compared with normal kidneys. Besides, CXCL13 expression was mainly detected in the glomerulus, specifically to mesangial areas. We then transfected a miR-155 mimic in human renal mesangial cells (HRMCs) to overexpress miR-155 and detected decreased protein levels of CXCR5 by western blot analysis. Transfection of the miR-155 mimic into CXCL13-treated HRMCs resulted in a significantly reduced proliferation rate of HRMCs as measured by the cell-counting assay and flow cytometry. Moreover, increased intracellular miR-155 also led to decreased phosphorylation of ERK and TGF-ß1 production. Together, these results revealed that miR-155 may play a role in the pathogenesis of LN.


Assuntos
Lúpus Eritematoso Sistêmico/metabolismo , Nefrite Lúpica/metabolismo , Células Mesangiais/citologia , MicroRNAs/farmacologia , Fator de Crescimento Transformador beta1/biossíntese , Animais , Proliferação de Células , Células Cultivadas , Quimiocina CXCL13/análise , Quimiocina CXCL13/farmacologia , Humanos , Rim/química , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Células Mesangiais/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos MRL lpr , Fosforilação , Receptores CXCR5/antagonistas & inibidores , Receptores CXCR5/metabolismo
15.
Braz. j. med. biol. res ; 52(4): e8131, 2019. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1001517

RESUMO

The leading cause of death in systemic lupus erythematosus (SLE) patients is infection. The objective of this study was to evaluate the distribution of lymphocyte subsets in untreated SLE patients with infections. This was a cross-sectional study. Data from January 2017 to May 2018 were collected. Flow cytometry was used to measure the peripheral lymphocyte subsets including CD3+T cells, CD4+T cells, CD8+T cells, CD19+B cells, CD3-CD16+CD56NK cells, and CD3+CD16+CD56NKT cells in 25 healthy controls and 52 treatment-naive SLE patients, among whom 13 were complicated with infections. Association between the lymphocyte subsets and infections was further analyzed. SLE patients with infections (n=13) showed a significantly higher incidence rate of fever (84.6 vs 28.2%) and serositis (84.6 vs 23.1%), increased level of erythrocyte sedimentation rate (60.5±30.1 vs 37.4±27.1 mm/h), serum C-reactive protein (CRP) (102.7±94.9 vs 9.4±14.9 mg/L), procalcitonin (PCT) (1.07±0.08 vs 0.16±0.13 μg/L), and lower blood hemoglobin (Hb) (93.0±20.5 vs 110.4±16.0 g/L) level compared with non-infection patients (n=39) (all P<0.05). In comparison with non-infectious SLE patients (387.9±261.6/μL), CD4+T cells count decreased significantly in infectious SLE patients (217.8±150.4/μL) (P<0.05), and it was negatively correlated with infection-related indicators including PCT (r=−0.573, P=0.041) and CRP (r=−0.596, P=0.032) levels. Our findings suggested that abnormalities of peripheral lymphocyte subsets were related to the immune disorder of lupus itself, regardless of immunosuppressive treatment. Monitoring lymphocyte subsets, especially CD4+T cells, may be helpful for identifying the presence of infection in SLE patients.


Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Adulto Jovem , Subpopulações de Linfócitos , Infecções/sangue , Lúpus Eritematoso Sistêmico/sangue , Valores de Referência , Proteína C-Reativa/análise , Estudos de Casos e Controles , Estudos Transversais , Fatores de Risco , Estatísticas não Paramétricas , Contagem de Linfócitos , Citometria de Fluxo , Pró-Calcitonina/sangue
16.
Clin Rheumatol ; 37(3): 597-605, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29116543

RESUMO

The objective of this study is to evaluate the remission rate and describe the current use of medication in a large cohort of rheumatoid arthritis (RA) patients under routine clinical care in China. RA patients were recruited from 40 large teaching hospitals nationwide in China. Data regarding RA disease activity, medication treatment, and adverse events were recorded using a standardized clinical data questionnaire. RA remission was evaluated by the 28 Joint Disease Activity Score DAS28-ESR Clinical Disease Activity Index (CDAI), Simplified Disease Activity Index (SDAI), and American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) remission criteria. A total of 1945 patients with RA were included in the study. The proportions of patients who fulfilled the DAS28-ESR, CDAI, SDAI, and ACR/EULAR remission criteria were 10.90%, 6.17%, 5.04% , and 1.75%, respectively. Most patients had taken at least one disease-modifying anti-rheumatic drug (DMARD), and the most common prescriptions included leflunomide (LEF) and methotrexate (MTX). DMARD combined with botanics were the most common and dominant strategy for RA management (29.16%). Overall, 433 patients (22.27%) had at least one adverse event. Gastrointestinal adverse events (41.27%) were the most frequently reported events. The incidence of side effects in patients using biologics DMARDs (bDMARDs) was significantly lower than that in those taking MTX, LEF, or sulfasalazine (SSZ). The remission rate of RA disease activity, as assessed in Chinese clinical practice, was very low. Adverse effects of the medicine occurred in approximately one in five RA patients, with bDMARDs were demonstrated to be the medication with the lowest side effects.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Metotrexato/uso terapêutico , Indução de Remissão , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Artrite Reumatoide/diagnóstico , China , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Adulto Jovem
17.
PLoS One ; 11(12): e0168619, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-28030595

RESUMO

OBJECTIVE: To identify early signs associated with poor prognosis in Chinese patients with systemic lupus erythematosus (SLE) through a large population-based follow-up study. METHODS: Medical records of > 2,500 SLE patients that first hospitalized between 1999-2009 were collected from 26 centers across Jiangsu province, China, and entered into a database. These patients were followed-up for 5 to 15 years, and those remained contact and had known survival status in 2015 were assessed for the association of factors presented at the initial hospitalization with mortality at two time points (≤1year and > 1year). The independency of mortality factors was evaluated using multivariate Cox regression analysis. RESULTS: Among 1,372 patients we assessed, 92.3% were women and 17.2% were deceased in 2015. The main causes of death were infection (30.1%), neuropsychiatric impairment (14.8%), renal failure (14.4%) and cardiopulmonary involvement (8.5%). Hazard ratios (HR) of independent predictors for mortality (≤1year and > 1year, respectively) included hospital presentation of neuropsychiatric involvement (2.03 and 1.91), cardiopulmonary involvement (1.94 and 1.61) and increased serum creatinine (2.52 and 2.58). Patients older than 45 years and with disease durations more than 2 years at admission had unfavorable short-term outcome (HR 1.76 and 1.79), while the presence of anti-dsDNA and anti-Sm antibodies indicated diverse prognosis after 1 year (HR 1.60 and 0.45). Treatment with cyclophosphamide was beneficial for patient's first-year outcome (HR 0.50), and anti-malarial drugs significantly reduced the risk of mortality over different time points (HR 0.48 and 0.54). SLEDAI score, proteinuria or hypocomplementemia was not independently associated with the outcome in this cohort. CONCLUSION: SLE patients presented with vital organ damages rather than active disease at initial hospitalization are likely to have a poor outcome, especially for those with neuropsychiatric, cardiopulmonary involvements and renal insufficiency. Early and effective intervention with the use of anti-malarial drugs may decrease mortality.


Assuntos
Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/terapia , Adulto , Causas de Morte , China , Estudos de Coortes , Feminino , Seguimentos , Hospitalização , Humanos , Lúpus Eritematoso Sistêmico/mortalidade , Masculino , Prognóstico , Fatores de Risco , Análise de Sobrevida
18.
J Immunol Res ; 2016: 2063985, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27672667

RESUMO

As a CXC subtype member of the chemokine superfamily, CXCL13 is considered to be involved in systemic lupus erythematosus (SLE), especially in lupus nephritis (LN). To determine the effect of CXCL13 on SLE and explore the potential mechanisms, we tested serum concentrations of CXCL13 in patients and healthy individuals and found that CXCL13 expression was high in SLE patients especially in LN patients. When we treated human renal mesangial cells (HRMCs) in vitro with recombinant human CXCL13, the cell proliferation was accelerated, which was tested by Cell Counting Kit-8 assay and flow cytometry. Western blot and immunofluorescence assay revealed that CXCL13 would lead to phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2). However, the effect was weakened after the silence of CXCR5. The results of our study elaborated that high expression of CXCL13 could be involved in the pathogenesis of LN.

19.
Patient Prefer Adherence ; 10: 879-85, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27284241

RESUMO

AIM: To evaluate the relationship between mental and physical health in Chinese patients with ankylosing spondylitis (AS) and to identify the predictors of psychological status. METHODS: Patients with AS (n=103) and healthy controls (n=121) were surveyed between 2010 and 2011 (cross-sectional study). The Bath Ankylosing Spondylitis Disease Activity Index, Bath Ankylosing Spondylitis Functional Index, Bath Ankylosing Spondylitis Metrology Index, pain visual analog scale, Health Assessment Questionnaire, revised Self-Rating Anxiety Scale, revised Self-Rating Depression Scale, and Short-Form 36 questionnaire were administered. RESULTS: The frequency of anxiety and depression in patients with AS was higher than that in healthy controls (P<0.001). Severe disease status and reduced quality of life (QoL) were associated with anxiety and depression. Disease activity and somatic pain were more severe in the anxious and depressed subgroups. Impaired physical functioning (assessed by Bath Ankylosing Spondylitis Functional Index) was higher in the anxious and depressed subgroups, while measures of spinal mobility (assessed by Bath Ankylosing Spondylitis Metrology Index) were not associated with depression. Lower QoL was observed in the depressed subgroup. CONCLUSION: Low socioeconomic status, lack of health insurance, and fatigue contributed to depression in Chinese patients with AS. These patients may require a psychological care approach that is different from those of other countries.

20.
Aging (Albany NY) ; 8(5): 1102-14, 2016 05.
Artigo em Inglês | MEDLINE | ID: mdl-27048648

RESUMO

We have shown that bone marrow (BM)-derived mesenchymal stem cells (BM-MSCs) from SLE patients exhibit senescent behavior and are involved in the pathogenesis of SLE. The aim of this study was to investigate the effects of rapamycin (RAPA) on the senescences and immunoregulatory ability of MSCs of MRL/lpr mice and SLE patients and the underlying mechanisms. Cell morphology, senescence associated ß-galactosidase (SA-ß-gal) staining, F-actin staining were used to detect the senescence of cells. BM-MSCs and purified CD4+ T cells were co-cultured indirectly. Flow cytometry was used to inspect the proportion of regulatory T (Treg) /T helper type 17 (Th17). We used small interfering RNA (siRNA) to interfere the expression of mTOR, and detect the effects by RT-PCR, WB and immunofluorescence. Finally, 1x106 of SLE BM-MSCs treated with RAPA were transplanted to cure the 8 MRL/lpr mice aged 16 weeks for 12 weeks. We demonstrated that RAPA alleviated the clinical symptoms of lupus nephritis and prolonged survival in MRL/lpr mice. RAPA reversed the senescent phenotype and improved immunoregulation of MSCs from MRL/lpr mice and SLE patients through inhibition of the mTOR signaling pathway. Marked therapeutic effects were observed in MRL/lpr mice following transplantation of BM-MSCs from SLE patients pretreated with RAPA.


Assuntos
Senescência Celular/efeitos dos fármacos , Imunossupressores/farmacologia , Lúpus Eritematoso Sistêmico/imunologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Sirolimo/farmacologia , Serina-Treonina Quinases TOR/metabolismo , Animais , Forma Celular/efeitos dos fármacos , Células Cultivadas , Modelos Animais de Doenças , Feminino , Humanos , Imunossupressores/uso terapêutico , Lúpus Eritematoso Sistêmico/metabolismo , Nefrite Lúpica/tratamento farmacológico , Nefrite Lúpica/imunologia , Nefrite Lúpica/metabolismo , Células-Tronco Mesenquimais/metabolismo , Camundongos , Camundongos Endogâmicos MRL lpr , Sirolimo/uso terapêutico , beta-Galactosidase/metabolismo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...