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1.
Clin Exp Rheumatol ; 37 Suppl 117(2): 109-115, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30943132

RESUMO

OBJECTIVES: To evaluate the association between disease activity and serum levels of pentraxin-3 (PTX-3) and lysosomal-associated membrane protein-2 (LAMP-2) as well as the acute reactants in Chinese Takayasu's arteritis (TAK) patients. METHODS: The serum PTX-3 and LAMP-2 levels were tested in 98 TAK patients and 40 age- and gender-matched healthy controls. The disease activity of these TAK patients was assessed according to the National Institute of Health (NIH) and Abatacept in giant cell arteritis and Takayasu's arteritis (AGATA) criteria, respectively. RESULTS: Among the 98 TAK patients, 45 and 52 patients had active disease according to the NIH criteria and AGATA criteria respectively. The total agreement rate between these two criteria was 90.82% (κ=0.817, p<0.001). Both serum PTX-3 and LAMP-2 levels were elevated in TAK patients compared with those in healthy controls (PTX- 3: 0.32±0.03 ng/ml vs. 0.18±0.02 ng/ ml, p=0.001; LAMP-2: 4.40±0.14 ng/ ml vs. 3.30±0.20 ng/ml, p<0.001). TAK patients with active disease had higher serum PTX-3 levels compared with those who had inactive disease (NIH criteria: 0.42±0.06 ng/ml vs. 0.25±0.02 ng/ml, p=0.004; AGATA criteria: 0.38±0.05 ng/ml vs. 0.27±0.02 ng/ml, p=0.049). However, serum LAMP-2 levels did not differ between patients with active and inactive disease according to both NIH and AGATA criteria. A cutoff value of PTX-3 with 0.30 ng/ml maximised the ability of disease activity assessment with a sensitivity/specificity of 57.10%/73.10% and 47.90%/71.10% according to the NIH and AGATA criteria, respectively. CONCLUSIONS: Serum PTX-3 and LAMP- 2 levels are elevated in Chinese TAK patients. However, serum PTX-3 but not LAMP-2 level is associated with active disease.


Assuntos
Proteína C-Reativa/metabolismo , Arterite de Células Gigantes , Proteína 2 de Membrana Associada ao Lisossomo/sangue , Componente Amiloide P Sérico/metabolismo , Arterite de Takayasu , Adulto , Biomarcadores , Estudos de Casos e Controles , Feminino , Arterite de Células Gigantes/sangue , Humanos , Masculino , Índice de Gravidade de Doença , Arterite de Takayasu/sangue
3.
Int J Rheum Dis ; 22 Suppl 1: 53-59, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29624875

RESUMO

Takayasu arteritis (TA) is a rare and chronic large-vessel vasculitis that predominantly affects aorta and its main branches. It occurs mainly in females <40 years. Precise assessment of disease activity is one of the major difficulties in the long-term management of TA. Until now, the accuracy of traditional activity index is still controversial. During these years, due to rapid development of radiological technology and researches of pathogenesis, new measurements and biomarkers have been applied to monitor disease activity for TA. Thus, in this review, we mainly discuss the benefits and limitations of recent developments of radiology and biomarkers for disease activity assessment in TA.


Assuntos
Angiografia/métodos , Artérias/diagnóstico por imagem , Artérias/metabolismo , Arterite de Takayasu/sangue , Arterite de Takayasu/diagnóstico por imagem , Ultrassonografia de Intervenção , Biomarcadores/sangue , Angiografia por Tomografia Computadorizada , Humanos , Angiografia por Ressonância Magnética , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Valor Preditivo dos Testes , Prognóstico , Reprodutibilidade dos Testes , Índice de Gravidade de Doença
4.
Clin Rheumatol ; 38(1): 143-148, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30171380

RESUMO

Takayasu arteritis (TA) is a chronic inflammatory disease. Interleukin (IL)-6 and IL-10 are important cytokines involved in the immune response of TA in some ethnicities. We investigated whether the single-nucleotide polymorphism (SNP) of IL-6 and IL-10 genes and their expressions were associated with TA in a Chinese Han population. One hundred eighty-four TA patients and 235 healthy controls (HC) were recruited. DNA and RNA were extracted from peripheral blood cells. Genotyping of IL-6 and -10 was performed using polymerase chain reaction-ligase detection reaction (PCR-LDR). The mRNA levels of IL-6 and IL-10 were semi-quantified using reverse transcription polymerase chain reaction (RT-PCR) and real-time polymerase chain reaction (real-time PCR). Plasma levels of them were examined by enzyme-linked immunosorbent assay (ELISA). The mRNA levels of IL-6 in active phase of TA were higher than those in stable phase (p = 0.015); the IL-10 in active phase was lower compared with stable phase (p = 0.046). Plasma levels of IL-6 in TA were higher than those in HC (p = 0.024). Plasma levels of IL-10 showed no difference between the two groups (p = 0.264). Plasma levels of IL-6 in active phase were increased than those in stable phase (p = 0.043) while those of IL-10 were decreased in active phase (p = 0.041). We found no significant differences between TA and HC in the frequency of any of the variations in the SNPs of IL-6 and IL-10 genes. The expression levels of both cytokines were associated with the disease status, indicating that they may serve as potential biomarkers for monitoring disease activity.


Assuntos
Interleucina-10/sangue , Interleucina-6/sangue , Arterite de Takayasu/sangue , Arterite de Takayasu/genética , Adulto , Alelos , Grupo com Ancestrais do Continente Asiático/genética , Biomarcadores/sangue , Estudos de Casos e Controles , China , Feminino , Humanos , Interleucina-10/genética , Interleucina-6/genética , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , RNA Mensageiro/análise , Adulto Jovem
5.
Int J Rheum Dis ; 22(8): 1371-1377, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30565885

RESUMO

AIM: To determine the diagnostic yield of 18 F-fluorodeoxyglucose positron emission tomography (PET) in disease activity assessment of large vessel vasculitides (LVV). METHODS: Patients with LVV who had undergone PET (between 2004 and June 2010) or PET co-registered with computed tomography (PET/CT; since June 2010) were identified. Clinical disease activity was assessed using established scoring systems. PET images were reviewed by two blinded nuclear medicine physicians. Uptake of the aortic wall was compared to the liver uptake utilizing a visual 4-point score, with a vessel wall uptake similar or higher than liver uptake considered as active disease. Various target-to-background ratios were calculated. Receiver operator characteristics analysis was applied to determine the diagnostic accuracy of PET for detecting clinically active disease. Interobserver agreement of visual readings was measured with Cohen´s kappa. RESULTS: Eighty examinations in 62 patients were analyzed, with a mean time between diagnosis and PET of 106 ± 171 weeks. Fifty-seven cases were finally classified as clinically active and 23 cases as clinically inactive. With a cut-off value of 1.3, the aorta-to-liver ratio yielded a sensitivity and specificity of 84.2% and 82.6% (area under the curve 0.9). Overall, sensitivity and specificity of visual analysis were 68.4% and 91.3%, but sensitivity decreased to 54% in patients treated for more than 3 months. Interobserver agreement of visual rating was excellent (κ: 0.93). CONCLUSION: Positron emission tomography is specific and reliable in disease activity assessment of LVV, but lacks sensitivity for detecting active disease in patients under long-term immunosuppressive treatment.


Assuntos
Aorta/diagnóstico por imagem , Arterite de Células Gigantes/diagnóstico por imagem , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Arterite de Takayasu/diagnóstico por imagem , Biomarcadores/sangue , Bases de Dados Factuais , Feminino , Fluordesoxiglucose F18/administração & dosagem , Arterite de Células Gigantes/sangue , Humanos , Masculino , Variações Dependentes do Observador , Valor Preditivo dos Testes , Prognóstico , Compostos Radiofarmacêuticos/administração & dosagem , Reprodutibilidade dos Testes , Estudos Retrospectivos , Índice de Gravidade de Doença , Arterite de Takayasu/sangue
6.
Zhonghua Xin Xue Guan Bing Za Zhi ; 46(9): 713-718, 2018 Sep 24.
Artigo em Chinês | MEDLINE | ID: mdl-30293378

RESUMO

Objective: To explore the relation between platelet-to-lymphocyte ratio (PLR) or neutrophil-to-lymphocyte ratio (NLR) with disease activity in Takayasu arteritis (TA) patients. Methods: Present retrospective study involved 289 patients with TA, who were hospitalized in our department between January 2010 and October 2017, and 280 age and gender matched healthy controls,who underwent thealth examination in our health examination center during the same period (control group). TA patients were further divided into active and inactive groups (180 and 109 cases respectively) according to Kerr scores. The clinical data were compared between groups. Pearson correlation analysis was used to evaluate the relationship between PLR or NLR and disease activity (Kerr score or C-reactive protein or erythrocyte sedimentation rate). Receiver operating characteristic (ROC) curve was employed to judge the cut-off value of disease activity for TA patients. Results: PLR and NLR were significantly higher in TA group than in control group(137.33 (97.38, 193.37) vs. 120.55 (96.86, 144.60) and 2.38 (1.76, 3.57) vs. 1.66 (1.35, 2.08) , respectively, all P<0.001). PLR and NLR were significantly higher in active TA group than in inactive TA group (163.43 (123.64, 224.15) vs. 110.53 (84.22, 147.24) and 2.59 (1.96, 3.94) vs. 1.95 (1.53, 2.86) respectively, all P<0.001). PLR and NLR of active group were significantly decreased after 6 months treatment (164.05 (123.29, 226.29) vs. 104.67 (77.22, 138.43) and 2.58 (1.96, 3.91) vs. 2.15 (1.67, 2.60) respectively, all P<0.001). PLR was positively correlated with Kerr score (r=0.439, P<0.001), C-reactive protein (r=0.328, P<0.001) and erythrocyte sedimentation rate (r=0.410, P<0.001). NLR also exhibited a positive relationship with Kerr score (r=0.235, P<0.001), C-reactive protein (r=0.169, P=0.005) and erythrocyte sedimentation rate (r=0.123, P=0.037). A PLR level of 176.709 was shown to be the best predictive cut-off value for TA disease activity (sensitivity 44.6%, specificity 93.0%, and area under the curve=0.766).A NLR level of 2.128 was shown to be the best predictive cut-off value for TA disease activity (sensitivity 70.9%, specificity 47.7%, and area under the curve=0.691). Conclusion: PLR and NLR are useful markers for predicting disease activity of TA patients.


Assuntos
Neutrófilos , Contagem de Plaquetas , Arterite de Takayasu , Plaquetas , Humanos , Linfócitos , Estudos Retrospectivos , Arterite de Takayasu/sangue
7.
Rheumatol Int ; 38(12): 2233-2242, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30229280

RESUMO

To evaluate the efficacy and safety of infliximab biosimilar CT-P13 in patients with active Takayasu arteritis (TAK). In this single-center open-label trial, patients with active TAK received CT-P13 at a starting dose of 5 mg/kg at weeks 0, 2, 6, and then every 8 weeks up to week 46. They were followed up until week 54. From week 14 to week 46, patients with inadequate response received increased dose of CT-P13 by 1.5 mg/kg. Concomitant prednisolone was allowed ≤ 10 mg/day. The primary efficacy end point was the achievement of partial or complete remission at week 30. All patients underwent positron emission tomography-computed tomography (PET-CT) at baseline and week 30. Twelve patients with TAK received CT-P13; one patient with protocol violation was excluded from analysis. Nine (81.8%) patients had taken concomitant prednisolone with median dose of 5.0 mg/day. At week 30, three (27.3%) patients achieved complete remission and six (54.5%) patients achieved partial remission. Statistically significant improvements in modified Indian Takayasu Clinical Activity Score (ITAS2010), ITAS-A, and serum levels of erythrocyte sedimentation rate and C-reactive protein were seen at week 30 from baseline. PET parameters were significantly reduced from baseline to week 30, including maximum standardized uptake value, target-to-vein ratio, target-to-liver ratio, and PET Vascular Activity Score. There were no serious adverse events. Treatment with CT-P13 may lead to improvement in clinical, radiographic, and serological activities with lower glucocorticoid requirement in TAK.Trial registration number NCT02457585.


Assuntos
Anti-Inflamatórios/administração & dosagem , Anticorpos Monoclonais/administração & dosagem , Medicamentos Biossimilares/administração & dosagem , Glucocorticoides/administração & dosagem , Prednisolona/administração & dosagem , Arterite de Takayasu/tratamento farmacológico , Adulto , Anti-Inflamatórios/efeitos adversos , Anticorpos Monoclonais/efeitos adversos , Biomarcadores/sangue , Medicamentos Biossimilares/efeitos adversos , Sedimentação Sanguínea , Proteína C-Reativa/metabolismo , Quimioterapia Combinada , Feminino , Glucocorticoides/efeitos adversos , Humanos , Mediadores da Inflamação/sangue , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Prednisolona/efeitos adversos , Estudos Prospectivos , Indução de Remissão , Arterite de Takayasu/sangue , Arterite de Takayasu/diagnóstico por imagem , Fatores de Tempo , Resultado do Tratamento
8.
J Proteome Res ; 17(9): 3317-3324, 2018 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-30095916

RESUMO

Takayasu arteritis (TA) is a large vessel vasculitis of unknown pathogenesis. Assessment of disease activity is a challenge, and there is an unmet need for relevant biomarker(s). In our previous study, NMR based serum metabolomics had revealed distinctive metabolic signatures in TA patients compared with age/sex matched healthy controls and systemic lupus erythematosus (SLE). In this study we investigate whether the metabolites correlate with disease activity. Patients with TA fulfilling American College of Rheumatology (ACR) criteria were enrolled, and disease activity was assessed using Indian Takayasu Clinical Activity Score using acute phase reactant-erythrocyte sedimentation rate [ITAS-A (ESR)]. Sera were analyzed using 800 MHz NMR spectrometer to identify metabolites [based on partial least squares discriminant analysis (PLS-DA) VIP (variable importance in projection) score > 1.0 and permutation test, p-value <0.01]. 45 active and 53 inactive TA patients with median age 27 [(IQR) 22-35 years] and 27 [(IQR) 23-37 years], female to male ratio 3.5:1 and 4.9:1, and median duration of illness 5 [(IQR) 2-9 years] and 3 [(IQR) 1-6 years], respectively, were enrolled. The key metabolites with highest discriminatory potential in active TA (ITAS-A ≥ 4) were glutamate and N-acetyl glycoprotein (NAG), both elevated, with area under the curve 0.775 and 0.769 ( p-value <0.001). On follow up assessment, metabolic spectra started to differ with change in disease activity. This large cohort of patients revealed metabolic profiles discriminating between clinically active and inactive TA patients. It suggests glutamate and NAG have strong potential as biomarkers for disease activity in TA and may serve as a guide to therapy. We are now working to further validate these results in longitudinal studies.


Assuntos
Ácido Glutâmico/sangue , Proteínas de Neoplasias/sangue , Arterite de Takayasu/sangue , Arterite de Takayasu/diagnóstico , Adulto , Área Sob a Curva , Biomarcadores/sangue , Sedimentação Sanguínea , Estudos de Casos e Controles , Progressão da Doença , Feminino , Humanos , Imunossupressores/uso terapêutico , Espectroscopia de Ressonância Magnética , Masculino , Metabolômica/métodos , Análise de Componente Principal , Índice de Gravidade de Doença , Arterite de Takayasu/imunologia , Arterite de Takayasu/fisiopatologia
9.
Clin Rheumatol ; 37(12): 3439-3442, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29998368

RESUMO

Despite many studies focused on involvement of T cell in pathogenesis of Takayasu arteritis (TaK), very few have explored the role of B cells. Hence, we sought evidence of B cell involvement in a large cohort of TaK by measuring serum levels of B cell survival factors activation factor (BAFF) and A proliferation inducing ligand (APRIL). Serum BAFF and APRIL levels were measured by ELISA in 50 patients and 48 healthy individuals, and further assessed for correlation with outcome measures, such as Indian Takayasu Clinical Activity Score-ESR (ITAS-ESR) and Takayasu arteritis Damage score (TADS). Forty women and ten men of median age 26 (11-52) and disease duration of 3 years (0.1-22) were studied. Type V disease was the most common subset (n = 31), while type I, II, III, and IV was seen in ten, four, three, and two patients respectively. Serum APRIL levels were raised in patients as compared to healthy controls [2087.5 pg/ml (1480.0-2279.0) vs. 1288.64 pg/ml, (844.2-1632.9) p = 0.01]. Median serum APRIL level was also raised in patients with active disease (n = 24) as compared to inactive disease (n = 26) 2098.79 pg/ml, (1930.75-2768.75) vs. 1802.5 pg/ml, (1066.75-2098); p = 0.03). Serum BAFF levels were not raised in patients with TaK when compared to healthy Individuals. Neither BAFF, nor APRIL levels correlated with disease activity (ITAS-ESR) or TADS. Elevated APRIL levels in active TaK suggest probable role of B cells in pathogenesis.


Assuntos
Fator Ativador de Células B/sangue , Arterite de Takayasu/sangue , Membro 13 da Superfamília de Ligantes de Fatores de Necrose Tumoral/sangue , Adolescente , Adulto , Estudos de Casos e Controles , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Adulto Jovem
10.
Int J Cardiol ; 266: 222-228, 2018 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-29729868

RESUMO

OBJECTIVE: To evaluate the treatment effects of the IL-6R antibody tocilizumab and cyclophosphamide (CTX) in patients with Takayasu arteritis (TA) and explore the mechanism by analyzing their effects on various cytokines. METHODS AND MATERIALS: This study included 9 TA patients treated with tocilizumab, 15 TA patients treated with CTX and 24 healthy controls. Treatment effects were evaluated based on: (1) Kerr score and Indian Takayasu Clinical Activity Score (ITAS2010), (2) improvement of previous lesions and occurrence of new vascular lesions on magnetic resonance angiography (MRA), (3) changes in various cytokine levels, (4) glucocorticoid sparing, and (5) adverse effects. ELISA was used to analyze the cytokine levels. RESULTS: Before treatment, all the patients had active disease accompanied with elevated C-reactive protein (CRP), serum amyloid A (SAA), interleukin (IL)-6 and pentraxin-3 (PTX3). Moreover, an imbalance in the MMP-TIMP system was also observed in these patients. Among them, IL-6 and MMP-9 levels were significantly associated with vascular enhancement scores and stenosis scores, respectively. At 6months after treatment, improved clinical manifestations and glucocorticoids sparing were observed in both groups without any severe side effects. Although no significant improvement occurred in the vascular stenosis, thickness and enhancement scores in both groups, a more degree of decrease of ESR, CRP level, significantly decreased MMP-9 level and increased MMP-2 level were found in the tocilizumab group than in the CTX group. CONCLUSIONS: The IL-6R antibody may be more effective in mitigating vascular inflammation and remodeling than CTX via inhibition of IL-6 and MMP-9.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Ciclofosfamida/uso terapêutico , Imunossupressores/uso terapêutico , Receptores de Interleucina-6/sangue , Arterite de Takayasu/diagnóstico por imagem , Arterite de Takayasu/tratamento farmacológico , Adulto , Anticorpos Monoclonais Humanizados/farmacologia , Estudos de Coortes , Feminino , Humanos , Angiografia por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Receptores de Interleucina-6/antagonistas & inibidores , Arterite de Takayasu/sangue , Resultado do Tratamento , Adulto Jovem
11.
Clin Rheumatol ; 37(10): 2789-2795, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29687289

RESUMO

The objective of the study was to investigate the long-term treatment effects and predictive factors for treatment response and disease relapse for Takayasu's arteritis (TA). Eighty-one patients were recruited from the Department of Rheumatology, Zhongshan Hospital, Fudan University, between January 2009 and January 2015. The follow-up duration ranged from 6 to 36 months. Patients were divided into three groups: clinical remission (CR; n = 59); treatment-resistant (TR; n = 11); and disease relapse (DR; n = 11). Signs/symptoms, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and imaging items were recorded at baseline and at each visit. Kerr's criteria, physician's global assessment, and Indian Takayasu Clinical Activity Score (ITAS2010) were used to evaluate disease activity. Incipient disease was more common in CR patients compared with DR cases (69.49 vs. 36.36%, p = 0.05). Fewer patients aged < 40 years were in the CR group in comparison with the DR group (57.63 vs. 90.91%, p = 0.04). In TR patients, high CRP levels (63.74 vs. 23.73%, p = 0.01) and aortic arch involvement (70.00 vs. 24.14%, p < 0.01) were more common in comparison with CR cases. Patients with high CRP levels (> 25 mg/L) (OR = 1.61, p = 0.03) carried a higher risk for treatment resistance. Age > 40 years (OR = - 2.82, p = 0.03), incipient disease (OR = - 2.47, p = 0.01), and treatment with cyclophosphamide (OR = - 2.07, p = 0.03) and hydroxychloroquine (OR = - 1.91, p = 0.05) could prevent disease relapse. Patients with high CRP levels carry a high risk of treatment resistance. In patients with incipient disease, aged > 40 years, treatment with cyclophosphamide and hydroxychloroquine protects against disease relapse.


Assuntos
Arterite de Takayasu/sangue , Arterite de Takayasu/tratamento farmacológico , Adulto , Fatores Etários , Benzimidazóis/uso terapêutico , Sedimentação Sanguínea , Proteína C-Reativa/análise , China , Ciclofosfamida/uso terapêutico , Resistência a Medicamentos , Feminino , Seguimentos , Humanos , Hidroxicloroquina/uso terapêutico , Imunossupressores/uso terapêutico , Masculino , Recidiva , Indução de Remissão , Prevenção Secundária , Arterite de Takayasu/complicações , Adulto Jovem
13.
Int J Rheum Dis ; 21(2): 532-540, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28425192

RESUMO

AIM: Disease activity assessment in Takayasu arteritis (TA) is challenging. Human leukocyte antigen E (HLA-E) is shed from endothelium into serum as a soluble molecule (sHLA-E) in response to inflammation. We aimed to study: (i) utility of sHLA-E as a biomarker of disease activity; and (ii) association of HLA-E polymorphism rs1264457 with clinical disease in Asian-Indian TA patients. MATERIALS AND METHODS: In phase-1, sHLA-E levels were estimated in sera of 50 consecutive TA patients at baseline visit and 27 healthy controls. Serial estimations were performed in 27 of them. In phase-2, DNA of 150 TA patients and 264 healthy controls were genotyped for rs1264457 polymorphism. RESULTS: At baseline visit, disease was classified as active, stable and grumbling in 23, 18 and nine patients, respectively. sHLA-E levels were higher in active TA (43; interquartile range [IQR]: 25.3-64.6) pg/mL) than stable disease (12.9; IQR: 7.6-21.6 pg/mL) (P = 0.001). At first follow-up visit, sHLA-E levels were numerically higher in active disease than stable disease (P = 0.06) but this trend was blunted at second follow-up. sHLA-E levels increased in 54% versus 25% of patients with persistently active/relapsing and persistent stable course, respectively. rs1264457 polymorphism was not associated with susceptibility to TA and did not affect sHLA-E levels. CONCLUSION: sHLA-E level is useful as a biomarker of disease activity and course in TA patients. rs1264457 polymorphism is neither associated with susceptibility nor did it influence sHLA-E levels in TA.


Assuntos
Antígenos de Histocompatibilidade Classe I/sangue , Arterite de Takayasu/sangue , Adulto , Grupo com Ancestrais do Continente Asiático/genética , Biomarcadores/sangue , Estudos de Casos e Controles , Feminino , Predisposição Genética para Doença , Antígenos de Histocompatibilidade Classe I/genética , Humanos , Índia/epidemiologia , Masculino , Fenótipo , Polimorfismo de Nucleotídeo Único , Valor Preditivo dos Testes , Arterite de Takayasu/diagnóstico , Arterite de Takayasu/etnologia , Arterite de Takayasu/genética , Adulto Jovem
14.
Adv Rheumatol ; 58(1): 24, 2018 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-30657078

RESUMO

BACKGROUND: Endothelial progenitor cells (EPCs) are responsible for endothelial damage repair. Takayasu's arteritis (TA) is a chronic inflammatory disease that affects large vessels. The aim of the study was to evaluate the number of EPCs and the levels of vascular endothelial growth factor (VEGF) and the relationship of these variables in patients with TA. METHODS: Thirty women with TA and 30 healthy controls were included. EPCs were assessed by flow cytometry and cell culture and VEGF quantification was performed by commercial ELISA kits. RESULTS: Ages of patients and controls were similar. The number of EPCs in patients and controls (median (interquartile range) were 0.0073% (0.0081%) vs. 0.0062% (0.0089%), p = 0.779 by flow cytometry and 27.0 (42.3) colony forming units (CFUs) vs. 27.0 (20.5) CFUs, p = 0.473 by cells culture, respectively. VEGF levels in patients and controls was 274.5 (395.5) pg/ml vs. 243.5 (255.3) pg/ml, p = 0.460. There was no difference in the number of EPCs and VEGF level between patients with active and inactive disease. There was a tendency of the number of angioblast-like EPCs in patients taking anti-TNFs to be higher; and in patients using methotrexate to be lower. CONCLUSION: No significant difference was found in the quantification of EPCs and VEGF levels in TA patients compared to controls, and no difference was observed between patients with active and inactive disease.


Assuntos
Células Progenitoras Endoteliais/citologia , Arterite de Takayasu/sangue , Fator A de Crescimento do Endotélio Vascular/sangue , Adulto , Anti-Inflamatórios/administração & dosagem , Brasil , Estudos de Casos e Controles , Contagem de Células , Estudos Transversais , Células do Cúmulo , Células Progenitoras Endoteliais/classificação , Feminino , Citometria de Fluxo , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Leflunomida/uso terapêutico , Pessoa de Meia-Idade , Monócitos/classificação , Monócitos/citologia , Prednisona/administração & dosagem , Células-Tronco , Arterite de Takayasu/dietoterapia , Arterite de Takayasu/patologia , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores
15.
Rheumatol Int ; 38(4): 623-630, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29196802

RESUMO

The aim of the study was to explore utility of serial serum myeloid-related protein 8/14 (MRP8/14) as a biomarker of clinical disease activity and angiographic progression in Takayasu arteritis (TA). Serum MRP8/14 levels were assayed by commercial ELISA for 85 TA patients and 24 healthy controls at baseline, and for 56 and 21 TA patients during follow-up visits R1 and R2, respectively. Disease was categorised as active, indeterminate and stable according to Indian Takayasu Arteritis score (ITAS 2010), ITAS-A(CRP) and angiography. Patients were divided into responders and non-responders/relapsers based on treatment response. Non-parametric tests were used for inter-group comparisons at baseline and during follow-up time points. Generalised Estimating Equation was used to study association between changes in serial MRP8/14 levels and disease activity. At baseline, median MRP8/14 levels were higher in patients with TA than healthy controls [7353 (4524 to11283) vs 4896 (3194 to 8474.5) ng/ml, p = 0.011]. Patients with active disease had higher levels [8552 (5463-12488)] than stable disease [5292.5 (3140.5-7310)], p = 0.002, and healthy controls [4896 (3194-8474.5)], p = 0.001. Changes in serial MRP8/14 level were associated with changes in disease activity, independent of steroid dose, p = 0.000. At R1, MRP 8/14 levels were lower than baseline in responders (n = 38) [9146.0 (6296.8-13693.8) vs 6501 (4314.8-8304.5), p = 0.004], but did not change in non-responders/relapsers (n = 14) [6693.5(4210.8-10516.3) vs 7755.0(5342-10741.0), p = 0.42]. Similar trend was observed at R2. MRP8/14 levels increased during follow-up in 66% and 26.3% of angiographic progressors and non-progressors, respectively. MRP8/14 in TA may act as a novel biomarker with prognostic implications.


Assuntos
Calgranulina A/sangue , Calgranulina B/sangue , Arterite de Takayasu/sangue , Adolescente , Adulto , Angiografia , Biomarcadores/sangue , Estudos de Casos e Controles , Progressão da Doença , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Índia , Estudos Longitudinais , Masculino , Valor Preditivo dos Testes , Prognóstico , Estudos Prospectivos , Esteroides/uso terapêutico , Arterite de Takayasu/diagnóstico por imagem , Arterite de Takayasu/tratamento farmacológico , Adulto Jovem
17.
Arthritis Res Ther ; 19(1): 197, 2017 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-28874185

RESUMO

BACKGROUND: A previous study revealed the association between susceptibility to Takayasu arteritis (TAK) and a single nucleotide polymorphism (SNP) rs6871626 located in IL12B, which encodes interleukin (IL)-12p40, a common component of IL-12p70 and IL-23. We investigated the expression of these cytokines in patients with TAK, stratifying them into those with or without the risk allele at the rs6871626 SNP. METHODS: Plasma levels of IL-12p40, IL-12p70, and IL-23 were quantified in 44 patients with TAK and 19 healthy controls (HCs) by enzyme-linked immunosorbent assays. Monocytes were obtained from 20 patients with TAK and 14 HCs, treated with interferon-γ (IFN-γ) and lipopolysaccharide, and then supernatant cytokines were quantified. In addition, the ratio of IFN-γ+ or IL-17A+ cells to CD4+ T cells was measured by flow cytometric analysis of peripheral blood mononuclear cells. RESULTS: The levels of plasma IL-12p40, plasma IL-12p70, and supernatant IL-12p70 were significantly higher in patients with TAK than in HCs, whereas there were no significant differences in the levels of plasma IL-23, supernatant IL-23, or supernatant IL-12p40. The levels of plasma IL-12p70, supernatant IL-12p40, and supernatant IL-12p70 were significantly higher in patients with the risk allele than in those without. The ratio of CD4+IFN-γ+ cells was significantly higher in patients with the risk allele, whereas CD4+IL-17A+ cells showed no differences. CONCLUSIONS: The rs6871626 SNP in IL12B may influence the increased expression of IL-12p40 and IL-12p70. These enhanced cytokines might play roles in the pathophysiology of TAK.


Assuntos
Loci Gênicos/genética , Predisposição Genética para Doença/genética , Subunidade p40 da Interleucina-12/genética , Interleucina-12/genética , Arterite de Takayasu/genética , Adulto , Biomarcadores/sangue , Feminino , Humanos , Interleucina-12/sangue , Subunidade p40 da Interleucina-12/sangue , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único/genética , Arterite de Takayasu/sangue , Arterite de Takayasu/fisiopatologia
18.
Rheumatol Int ; 37(10): 1643-1649, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28801814

RESUMO

Assessment of disease activity in Takayasu arteritis (TA) is challenging. We aimed to study utility of serum amyloid A (SAA) to assess disease activity and its association with SAA gene polymorphisms, if any, in our TA patients. Serum of 99 consecutive adult TA patients and 40 healthy controls were assayed for SAA. Depending on the ITAS2010 and ITAS-CRP score, patients were designated as having active disease if ITAS2010 ≥ 2 or ITAS-CRP ≥ 3 and stable disease if ITAS2010 = 0 or ITAS-CRP is ≤1. Clinical ITAS of 0 with raised inflammatory markers scoring a ITAS-CRP of 2 was considered as indeterminate for disease activity assessment. Repeat SAA levels for active group was measured after 6 months from baseline. SAA levels between active and stable disease as well as serial levels were compared. DNA of 40 patients and controls were genotyped for SAA polymorphisms (rs12218, rs2468844) and the allele frequencies were compared. At baseline, SAA levels were higher in patients as compared to controls (137.4 vs 100.8 ng/ml, p = 0.001) and higher in patients with active disease (166.4 ng/ml) than those with stable disease (98.2 ng/ml), p = 0.001. SAA decreased during follow-up in treatment responders (189.9 ng/ml at baseline vs 119.0 ng/ml at follow-up, p = 0.008); in contrast, there was no significant change among non-responders during follow-up. Allelic frequencies of SAA gene polymorphisms did not differ between cases and controls. SAA may be a reliable biomarker to assess disease activity and treatment response in TA.


Assuntos
Imunossupressores/uso terapêutico , Proteína Amiloide A Sérica/metabolismo , Arterite de Takayasu/sangue , Adulto , Biomarcadores/sangue , Progressão da Doença , Feminino , Frequência do Gene , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo Genético , Proteína Amiloide A Sérica/genética , Índice de Gravidade de Doença , Arterite de Takayasu/diagnóstico , Arterite de Takayasu/tratamento farmacológico , Arterite de Takayasu/genética , Resultado do Tratamento , Adulto Jovem
20.
Int Heart J ; 58(4): 589-592, 2017 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-28701681

RESUMO

The integral changes of coagulation and fibrinolysis, and their relationships with inflammation in patients with Takayasu arteritis (TA) remain undetermined. The purpose of this study was to analyze the changes of coagulation and fibrinolysis process in patients with TA by thrombelastography (TEG).A total of 127 patients with TA and 55 healthy controls were enrolled. Patients with TA were grouped according to disease activity. The routine hematological parameters, traditional coagulation assays, and TEG parameters were summarized retrospectively.A shorter K time, larger alpha angle, and higher levels of MA, MA(A), G, and TPI were found in patients with TA, especially in those at the active stage. The R time, EPL, LY30, and CL30 were similar between patients with TA and healthy controls, as well as TA patients with different disease activity. Spearman's correlation showed that ESR was correlated with PLT (r = 0.206, P = 0.020), K (r = -0.353, P < 0.001), alpha angle (r = 0.328, P < 0.001), MA (r = 0.474, P < 0.001), MA (A) (r = 0.623, P < 0.001), G (r = 0.475, P < 0.001), and TPI (r = 0.458, P < 0.001).In conclusion, inflammation was associated with platelet coagulation function rather than enzymatic coagulation function in patients with TA. Physicians should focus on antiplatelet treatment for improving the prognosis of patients with TA.


Assuntos
Coagulação Sanguínea , Plaquetas/metabolismo , Inflamação/sangue , Ativação Plaquetária/fisiologia , Arterite de Takayasu/sangue , Humanos , Estudos Retrospectivos , Tromboelastografia
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