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1.
Clin Rheumatol ; 2019 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-31428886

RESUMO

INTRODUCTION: Contrast-enhanced ultrasound (CEUS) was recently used to evaluate vascularization within the carotid artery wall, and this process of vascularization was correlated with arteritis activity. We aimed to use CEUS to evaluate disease activity in Takayasu arteritis (TAK) patients. METHOD: We used CEUS to analyze 28 consecutive TAK patients. Disease activity was assessed according to the NIH criteria. We measured CEUS grades and assessed the correlation between contrast features and disease activity. RESULTS: Higher erythrocyte sedimentation rates (ESRs) were found (35 ± 28.7 vs. 13 ± 7.4 mm/h, p < 0.01), and CEUS carotid wall enhancement was more frequently (100% vs. 36.6%, p < 0.01) seen in TAK patients in the active phase than in those in the inactive phase. With increasing CEUS grades, both the artery wall thickness and ESR increased, and patients were more likely to be in the active phase (0 in grade 0, 42.9% in grade 1, and 75% in grade 2). Receiver operating characteristic (ROC) curve analysis showed that CEUS had an area under the ROC curve (AUC) of 0.872 (95% CI 0.785-0.959, p < 0.01), demonstrating good diagnostic accuracy. CONCLUSIONS: Higher CEUS grades reliably identify patients with active TAK. Key Points • No CEUS vascularization is obviously relative with the inactive disease of TAK patients. • Obvious CEUS vascularization is obviously relative with the active disease of TAK patients.

2.
World J Gastroenterol ; 23(48): 8489-8499, 2017 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-29358857

RESUMO

AIM: To explore the pathogenesis of primary biliary cholangitis (PBC) by identifying candidate autoantibodies in serum samples by proteomics and bioinformatics. METHODS: Nine antimitochondrial antibody (AMA)-positive PBC patients and nine age- and sex-matched AMA-negative PBC patients were recruited. Antigen enrichment technology was applied to capture autoantigens of human intrahepatic biliary epithelial cells (HiBECs) that are recognized by autoantibodies from the sera of PBC patients. Candidate autoantigens were identified by label-free mass spectrometry. Bioinformatics analysis with MaxQuant software (version 1.5.2.8), DAVID platform, and Cytoscape v.3.0 allowed illustration of pathways potentially involved in the pathogenesis of PBC. RESULTS: In total, 1081 candidate autoantigen proteins were identified from the PBC patient pool. Among them, 371 were determined to be significantly differentially expressed between AMA-positive and -negative PBC patients (P < 0.05). Fisher's exact test was performed for enrichment analysis of Gene Ontology protein annotations (biological processes, cellular components, and molecular functions) and the Kyoto Encyclopedia of Genes and Genomes pathways. Significantly different protein categories were revealed between AMA-positive and -negative PBC patients. As expected, autoantigens related to mitochondria were highly enriched in AMA-positive PBC patients. However, lower levels of AMA were also detected in AMA-negative PBC patients. In addition, autoantigens of AMA-negative PBC patients were mainly involved in B-cell activation, recognition of phagocytosis, and complement activation. CONCLUSION: AMA-negative PBC individuals may not exist, but rather, those patients exhibit pathogenesis pathways different from those of AMA-positive PBC. Comprehensive research is needed to confirm these observations.


Assuntos
Autoanticorpos/sangue , Autoantígenos/imunologia , Colangite/imunologia , Mitocôndrias/imunologia , Proteômica/métodos , Autoanticorpos/imunologia , Células Cultivadas , Colangite/sangue , Biologia Computacional , Ensaio de Imunoadsorção Enzimática , Células Epiteliais/imunologia , Humanos , Fígado/citologia , Fígado/imunologia , Espectrometria de Massas/métodos , Projetos Piloto , Software
3.
Medicine (Baltimore) ; 94(44): e1888, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26554784

RESUMO

T helper (Th) 17 cells were reported to have the property of proinflammation and profibrosis. We first investigate the levels of Th17 cells in primary biliary cirrhosis (PBC) patients, and then explore their distribution and fibrotic role in the disease.We compared the circulating Th17 and hepatic interleukin (IL)-17-positive cells between patients and healthy controls (HCs) at different disease stages by flow cytometry and immunohistochemistry, respectively. The levels of chemokine (c-c motif) ligand (CCL) 20 were then measured. For exploration of the reason why Th17 cells increased, CD4CD161 populations were sorted and cultured with IL-23 and IL-1ß to analyze their proliferation and IL-17 secretions. The serum IL-23 and IL-1ß were tested by enzyme-linked immunosorbent assay. The proliferation and expressions of α-smooth muscle actin and IL-8 of hepatic stellate cells (HSCs) were identified after stimulated by different concentrations of IL-17.Circulating and hepatic Th17 cells were elevated in PBC patients compared with HCs. Early PBC patients presented with more Th17 cells in periphery blood and less in the liver than advanced PBC patients. Accordingly, the levels of both serum and hepatic CCL20 for Th17 cells were higher, especially in those with advanced disease. The progenitor of Th17, CD4CD161 cell was increased in PBC. Moreover, the percentage of Th17 cells was positively related with CD4CD161 cell. After stimulation with IL-23 and IL-1ß which were improved in PBC patients, CD4CD161 cells from PBC patients expressed more IL-17, although their proliferation were not different between 2 groups. IL-17 can promote the proliferation of HSCs at a dose-dependent method, and also increase the IL-8 expression in a dose/time-dependent way. Anti-IL-17 can neutralize the above reactions.CD4CD161 cells are a source of increased Th17 in PBC patients. With disease progression, Th17 population decreased in the circulation, accompanied by greater accumulation in the liver, which is regulated by CCL20 in advanced patients. IL-17 may be involved in the process of PBC fibrosis.


Assuntos
Imunidade Celular , Interleucina-17/metabolismo , Cirrose Hepática Biliar/imunologia , Fígado/metabolismo , Células Th17/imunologia , Adulto , Células Cultivadas , Progressão da Doença , Ensaio de Imunoadsorção Enzimática , Feminino , Citometria de Fluxo , Humanos , Imuno-Histoquímica , Fígado/imunologia , Fígado/patologia , Cirrose Hepática Biliar/metabolismo , Masculino , Células Th17/metabolismo
4.
J Rheumatol ; 41(11): 2208-13, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25128511

RESUMO

OBJECTIVE: Characterized by chronic inflammation, dysfunction of exocrine glands, and systemic autoimmunity, primary Sjögren syndrome (pSS) is a common autoimmune disease in elderly women. Our study was performed to explore the potential involvement of microRNA (miRNA) in Chinese patients with pSS. METHODS: Using microarrays, miRNA expression in peripheral blood mononuclear cells (PBMC) was profiled in 4 female patients with pSS and 3 healthy participants, followed by a large-scale study of 33 patients and 10 healthy individuals. Compared to the healthy participants, 202 miRNA were upregulated and 180 were downregulated in the patients with pSS. To confirm this finding, a set of regulated miRNA was further examined in a large patient group, using quantitative reverse transcriptase-PCR assays. RESULTS: MiR-181a was the miRNA that most profoundly differed between patients with pSS and healthy individuals; however, similar miRNA-181a expression profiles were found in groups with different disease phenotypes. Together, these observations suggested that an elevated miRNA-181a level is a general phenomenon in Chinese patients with pSS. CONCLUSION: In addition to the elevated miR-181a levels, our study led to the speculation that elevated miR-181a levels in the PBMC of these patients compromise the maturation of B cells, enabling them to recognize and attack autoantigens and resulting in disease phenotypes. In addition to the regulation of human miRNA, many virus-derived miRNA were unexpectedly upregulated in the patients with pSS, suggesting that viral infection of PBMC plays a role in this disease.


Assuntos
Perfilação da Expressão Gênica , Leucócitos Mononucleares/metabolismo , MicroRNAs/metabolismo , Síndrome de Sjogren/fisiopatologia , Adulto , Estudos de Casos e Controles , Feminino , Marcadores Genéticos/genética , Humanos , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade , Prognóstico , Reação em Cadeia da Polimerase em Tempo Real/métodos , Valores de Referência , Medição de Risco , Índice de Gravidade de Doença , Síndrome de Sjogren/genética , Síndrome de Sjogren/imunologia , Estatísticas não Paramétricas , Regulação para Cima
5.
Stem Cells Dev ; 23(20): 2482-9, 2014 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-24835895

RESUMO

The objective of this study was to evaluate the safety and efficacy of allogeneic bone marrow mesenchymal stromal/stem cell transplantation (BM-MSCT) for patients with ursodeoxycholic acid (UDCA)-resistant primary biliary cirrhosis (PBC). Ten patients were enrolled in this trial of BM-MSCT. All patients were permitted to concurrently continue their previous UDCA treatment. The efficacy of BM-MSCT in UDCA-resistant PBC was assessed at various time points throughout the 12-month follow up. No transplantation-related side effects were observed. The life quality of the patients was improved after BM-MSCT as demonstrated by responses to the PBC-40 questionnaire. Serum levels of ALT, AST, γ-GT, and IgM significantly decreased from baseline after BM-MSCT. In addition, the percentage of CD8+ T cells was reduced, while that of CD4+CD25+Foxp3+ T cells was increased in peripheral lymphocytic subsets. Serum levels of IL-10 were also elevated. Notably, the optimal therapeutic outcome was acquired in 3 to 6 months and could be maintained for 12 months after BM-MSCT. In conclusion, allogeneic BM-MSCT in UDCA-resistant PBC is safe and appears to be effective.


Assuntos
Transplante de Medula Óssea , Colagogos e Coleréticos/administração & dosagem , Resistência a Medicamentos , Cirrose Hepática Biliar/terapia , Transplante de Células-Tronco Mesenquimais , Ácido Ursodesoxicólico/administração & dosagem , Adulto , Feminino , Seguimentos , Humanos , Cirrose Hepática Biliar/sangue , Masculino , Pessoa de Meia-Idade
6.
World J Gastroenterol ; 19(31): 5131-7, 2013 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-23964148

RESUMO

AIM: To establish the frequency and clinical features of connective tissue diseases (CTDs) in a cohort of Chinese patients with primary biliary cirrhosis (PBC). METHODS: Three-hundred and twenty-two Chinese PBC patients were screened for the presence of CTD, and the systemic involvement was assessed. The differences in clinical features and laboratory findings between PBC patients with and without CTD were documented. The diversity of incidence of CTDs in PBC of different countries and areas was discussed. For the comparison of normally distributed data, Student's t test was used, while non-parametric test (Wilcoxon test) for the non-normally distributed data and 2 × 2 χ(2) or Fisher's exact tests for the ratio. RESULTS: One-hundred and fifty (46.6%) PBC patients had one or more CTDs. The most common CTD was Sjögren's syndrome (SS, 121 cases, 36.2%). There were nine cases of systemic sclerosis (SSc, 2.8%), 12 of systemic lupus erythematosus (SLE, 3.7%), nine of rheumatoid arthritis (RA, 2.8%), and 10 of polymyositis (PM, 3.1%) in this cohort. Compared to patients with PBC only, the PBC + SS patients were more likely to have fever and elevated erythrocyte sedimentation rate (ESR), higher serum immunoglobulin G (IgG) levels and more frequent rheumatoid factor (RF) and interstitial lung disease (ILD) incidences; PBC + SSc patients had higher frequency of ILD; PBC + SLE patients had lower white blood cell (WBC) count, hemoglobin (Hb), platelet count, γ-glutamyl transpeptidase and immunoglobulin M levels, but higher frequency of renal involvement; PBC + RA patients had lower Hb, higher serum IgG, alkaline phosphatase, faster ESR and a higher ratio of RF positivity; PBC + PM patients had higher WBC count and a tendency towards myocardial involvement. CONCLUSION: Besides the common liver manifestation of PBC, systemic involvement and overlaps with other CTDs are not infrequent in Chinese patients. When overlapping with other CTDs, PBC patients manifested some special clinical and laboratory features which may have effect on the prognosis.


Assuntos
Doenças do Tecido Conjuntivo/epidemiologia , Cirrose Hepática Biliar/epidemiologia , Distribuição de Qui-Quadrado , China/epidemiologia , Doenças do Tecido Conjuntivo/diagnóstico , Humanos , Incidência , Cirrose Hepática Biliar/diagnóstico , Estudos Retrospectivos
7.
Hepatology ; 58(1): 264-72, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23408380

RESUMO

UNLABELLED: The biochemical response to ursodeoxycholic acid (UDCA) in primary biliary cirrhosis is a strong predictor of long-term outcome and thus facilitates the rapid identification of patients needing new therapeutic approaches. Numerous criteria for predicting outcome of treatment have been studied based on biochemical response to UDCA at 1 year. We sought to determine whether an earlier biochemical response at 3 or 6 months could as efficiently identify patients at risk of poor outcome, as defined by liver-related death, liver transplantation, and complications of cirrhosis. We analyzed the prospectively collected data of 187 patients with a median follow-up of 5.8 years (range, 1.3-14 years). The survival rates without adverse outcome at 5 years and 10 years were 86% and 63%. Under UDCA therapy, laboratory liver parameters experienced the most prominent improvement in the first 3 months (P < 0.0001) and then stayed relatively stable for the following months. The Paris, Barcelona, Toronto, and Ehime definitions, but not the Rotterdam definition, applied at 3, 6, and 12 months significantly discriminated the patients in terms of long-term outcome. Compared with biochemical responses evaluated after 1 year of UDCA therapy, biochemical responses at the third month demonstrated higher positive predictive value (PPV) but lower negative predictive value (NPV) and increased negative likelihood ratio (NLR) by all definitions; biochemical responses at the sixth month showed higher or the same PPV and NPV and lower NLR by all definitions. CONCLUSION: For the previously published criteria, biochemical responses at the sixth month can be used in place of those evaluated after 1 year of UDCA therapy. Our findings justify a more rapid identification of patients who need new therapeutic approaches.


Assuntos
Cirrose Hepática Biliar/tratamento farmacológico , Cirrose Hepática Biliar/metabolismo , Ácido Ursodesoxicólico/uso terapêutico , Adulto , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico
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