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1.
Int J Rheum Dis ; 22 Suppl 1: 60-68, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30698358

RESUMO

Takayasu arteritis (TA) is a challenging large vessel vasculitis to treat. Distinguishing disease activity from vascular damage is difficult, often relying on clinician judgement aided by composite clinical disease activity indices with angiographic evidence of vessel wall thickening or vessel wall hypermetabolism demonstrable on positron emission tomography computerized tomography (PET CT). Glucocorticoids form the mainstay of remission induction. While other conventional disease modifying anti-rheumatic drugs (cDMARDs) or biologic DMARDs (bDMARDs) are commonly used, evidence supporting their usefulness is sparse and generally of low quality. The only two randomized controlled trials (RCT) of a DMARD in TA failed to show efficacy of abatacept in reducing relapses of TA, however, tocilizumab showed a trend towards reduction in time to relapses. Of the cDMARDs, methotrexate, azathioprine, mycophenolate mofetil (MMF), leflunomide and cyclophosphamide have shown clinical efficacy in case series, with some evidence that methotrexate, azathioprine and MMF might retard angiographic progression. Among bDMARDs, anti-tumor necrosis factor alpha agents and tocilizumab may be useful in patients refractory to cDMARDs with retardation of angiographic progression, based on evidence derived from mostly retrospective case series, whereas the role of rituximab and ustekinumab needs further elucidation. Revascularization, either surgical or endovascular, is the treatment of choice to relieve critical, symptomatic stenoses and are best undertaken during inactive disease. Emerging evidence suggests that patients with TA also have increased cardiovascular risk and this requires appropriate management. Large studies involving multiple centers are the need of the hour to appropriately evaluate utility of currently available immunosuppressive therapy in TA.


Assuntos
Antirreumáticos/uso terapêutico , Produtos Biológicos/uso terapêutico , Imunossupressores/uso terapêutico , Arterite de Takayasu/tratamento farmacológico , Antirreumáticos/efeitos adversos , Produtos Biológicos/efeitos adversos , Humanos , Imunossupressores/efeitos adversos , Indução de Remissão , Índice de Gravidade de Doença , Arterite de Takayasu/diagnóstico , Arterite de Takayasu/imunologia , Resultado do Tratamento , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Fator de Necrose Tumoral alfa/imunologia
2.
Int J Rheum Dis ; 22 Suppl 1: 41-48, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29624864

RESUMO

Giant cell arteritis (GCA) and Takayasu arteritis (TAK) are forms of large-vessel vasculitides that affect the aorta and its branches. There is ongoing debate about whether they are within a spectrum of the same disease or different diseases. Shared commonalities include clinical features, evidence of systemic inflammation, granulomatous inflammation on biopsy, role of T-helper (Th)-1 and Th17 in the pathogenesis, and, abnormalities of the aorta and its branches on imaging. However, there are also several differences in the geographic distribution, genetics, inflammatory cells and responses to treatment. This review highlights the similarities and differences in the epidemiology, pathogenesis, clinical manifestations, imaging findings and treatment responses in these conditions. Current data supports that they are two distinct conditions despite the numerous similarities.


Assuntos
Arterite de Células Gigantes/diagnóstico , Arterite de Takayasu/diagnóstico , Adolescente , Adulto , Idade de Início , Diagnóstico Diferencial , Feminino , Arterite de Células Gigantes/tratamento farmacológico , Arterite de Células Gigantes/epidemiologia , Arterite de Células Gigantes/imunologia , Humanos , Imunossupressores/uso terapêutico , Masculino , Pessoa de Meia-Idade , Fenótipo , Valor Preditivo dos Testes , Arterite de Takayasu/tratamento farmacológico , Arterite de Takayasu/epidemiologia , Arterite de Takayasu/imunologia , Resultado do Tratamento , Adulto Jovem
3.
J Invest Surg ; 32(3): 220-227, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29313449

RESUMO

OBJECTIVE: To analyze the clinical outcome of corticosteroid and/or immunosuppressive treatment preoperatively in patients with Takayasu's arteritis. PATIENTS AND METHODS: Forty-six patients with Takayasu's arteritis who received cardiovascular surgery between January 2010 and December 2015 in Beijing Anzhen Hospital were enrolled in this study. Their clinical characteristics, preoperative drug therapy, surgical treatment, and pathological examination results were retrospectively analyzed for the effect of drugs on outcome of the surgery. RESULTS: All 8 patients with active disease prior to surgery had postoperative complications including one death due to stubborn perivalvular regurgitation induced heart failure during the perioperative period. Among 38 patients without active disease prior to surgery, only 4 patients (10.5%) had postoperative complications. Thirty-four patients showed symptomatic relief in the perioperative period, of whom 23 patients treated with corticosteroid and/or immunosuppressive agents preoperatively. CONCLUSION: The surgery can effectively improve the symptoms of patients with Takayasu's arteritis. Active disease of Takayasu's arteritis markedly increased risk for postoperative complication and resulted in poor outcome of the surgery. Treatment with corticosteroid and/or immunosuppressive agents before surgery can effectively control the patient's condition, improve the rate of remission, and effectively reduce the incidence of postoperative complications.


Assuntos
Procedimentos Cirúrgicos Cardiovasculares/efeitos adversos , Glucocorticoides/administração & dosagem , Imunossupressores/administração & dosagem , Complicações Pós-Operatórias/epidemiologia , Cuidados Pré-Operatórios/métodos , Arterite de Takayasu/cirurgia , Adulto , Feminino , Humanos , Masculino , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , Estudos Retrospectivos , Arterite de Takayasu/tratamento farmacológico , Arterite de Takayasu/imunologia , Resultado do Tratamento , Adulto Jovem
4.
Rheumatol Int ; 38(12): 2337-2343, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30276424

RESUMO

Corticosteroids rank at the first place among the most commonly used immunosuppressive agents in the rheumatology practice. Although their conventional adverse effects including hyperglycemia, hypertension, hyperlipidemia, and osteoporosis are well-recognized and managed, steroid-induced cardiac arrhythmias are known to a lesser extent. In this regard, steroid-associated bradycardia is rarely expected and not very well known. Reported cases of steroid-associated bradycardias in the literature predominantly have emerged during the course of intravenous high-dose (pulse) methylprednisolone (MP) administrations. In this paper, we report a patient who developed sinus bradycardia following 52 mg of oral MP administration, improved once the drug was discontinued but repeated with the re-administration. Hence, the patient was shifted to prednisolone (PRED), and again suffered bradycardia which recovered upon dose reduction. Presenting this case along with other similar rare cases in the literature, our aim is to draw attention of fellow rheumatologists, who widely use steroids, to bradycardia-a rare and dose-dependent side effect of steroids.


Assuntos
Corticosteroides/efeitos adversos , Bradicardia/induzido quimicamente , Frequência Cardíaca/efeitos dos fármacos , Metilprednisolona/efeitos adversos , Prednisolona/efeitos adversos , Arterite de Takayasu/tratamento farmacológico , Corticosteroides/administração & dosagem , Adulto , Bradicardia/diagnóstico , Bradicardia/fisiopatologia , Relação Dose-Resposta a Droga , Esquema de Medicação , Substituição de Medicamentos , Feminino , Humanos , Metilprednisolona/administração & dosagem , Prednisolona/administração & dosagem , Arterite de Takayasu/diagnóstico , Arterite de Takayasu/imunologia
5.
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
6.
Ann Vasc Surg ; 51: 314-319, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29783032

RESUMO

Friedrich Wilhelm Nietzsche (Röcken 1844 -Weimar 1900), the philosopher who theorized the concept of "eternal recurrence", suffered a lifelong multifaceted chronic illness that started in pediatric age with severe headaches and ended up with stroke at the age of 56. Even though many hypothetical diagnosis have been proposed in recent years, they all failed to explain the totality of clinical conditions that co-occurred in the philosopher's extremely challenging case, and debate on the matter is still open. In this report, we suggest an autoimmune condition, specifically Takayasu's arteritis, as a possible etiology of the philosopher's illness, which could not only potentially fit all available clinical data but also be the medical counterpart of Nietzsche's philosophical thought: could eternal recurrence of arteritis explain Zarathustra's destiny? If so, could a vascular surgeon, at this time in future, be so superhuman to change it?


Assuntos
Autoimunidade , Pessoas Famosas , Filosofia/história , Arterite de Takayasu/história , Efeitos Psicossociais da Doença , Progressão da Doença , História do Século XIX , Humanos , Fatores de Risco , Arterite de Takayasu/diagnóstico , Arterite de Takayasu/imunologia , Arterite de Takayasu/cirurgia , Procedimentos Cirúrgicos Vasculares/história
7.
Clin Exp Rheumatol ; 36 Suppl 111(2): 12-32, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29799395
8.
Clin Exp Rheumatol ; 36 Suppl 111(2): 33-39, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29600943

RESUMO

OBJECTIVES: To evaluate serum cytokines as biomarkers of smoldering disease activity in patients with Takayasu's arteritis (TAK) in remission. METHODS: Thirty-four TAK patients with stable disease during the last 6 months and 22 healthy controls (HC) were included in a cross-sectional study. Serum levels of pro-inflammatory, anti-inflammatory, Th1, Th2, Th9, Th17 and Th22 cytokines were measured by the multiplex technique. RESULTS: No significant differences regarding serum cytokine levels were found between TAK patients and HC. Serum TNF-α, IL-17F, IL-21 and IL-23 were higher in patients presenting angiographic type V than in those presenting other angiographic types. Serum IL-17E, IL-17F, IL-22 and IL-23 were higher in TAK patients with previous ischaemic events compared with those without previous ischaemia. No differences in serum cytokines were observed between TAK patients with and without aneurysmal disease in the aorta or among TAK patients without therapy, those under immunosuppressive agents and patients on biological therapy. Independent associations were found regarding angiographic type V and higher serum levels of IL-4, IL-6, IL17A, IL-17E, IL-17F, IL-21, IL-22 and IL-23. Previous ischaemic events were independently associated with higher serum IL-4, IL-17E, IL-22 and IL-23. Daily prednisone dose had an inverse association with lower serum IL-4, IL6, IL-17A, IL-17E, IL-22 and IL-23. The simultaneous use of immunosuppressive and biological agents led to lower serum IL-4, IL-17E and IL-23 levels. CONCLUSIONS: A smoldering inflammatory response with predominantly cytokines involved in Th17 response seems to be ongoing in TAK patients in remission with extensive disease or with previous ischaemic events.


Assuntos
Doenças Assintomáticas , Citocinas/imunologia , Inflamação/imunologia , Arterite de Takayasu/imunologia , Adulto , Estudos de Casos e Controles , Estudos Transversais , Feminino , Humanos , Interleucina-17/imunologia , Interleucina-23/imunologia , Interleucina-4/imunologia , Interleucina-6/imunologia , Interleucinas/imunologia , Masculino , Pessoa de Meia-Idade , Indução de Remissão , Fator de Necrose Tumoral alfa/imunologia
9.
Clin Exp Rheumatol ; 36 Suppl 111(2): 88-92, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29465347

RESUMO

OBJECTIVES: The commonly adopted method of defining active disease in Takayasu's arteritis (TAK) is the definition used by the US National Institutes of Health (NIH). A gold standard in imaging techniques for assessing disease activity in TAK has not been clearly established and the creation of practical and valid tools represents a challenge. To assess whether 18F-FDG-PET/CT and NIH criteria show a good level of agreement in assessing disease activity of TAK patients. METHODS: 18F-FDG-PET/CT was performed in 17 patients with TAK. All 17 patients fulfilled the clinical criteria according to the American College of Rheumatology criteria. Two nuclear physicians visually assessed the degree of 18F-FDG uptake in the inflammatory vascular lesion. 18F-FDG-PET/CT and the inflammatory vascular lesion were evaluated by using the standardised uptake value (SUV) of 18F-FDG accumulation were interpreted as active vasculitic lesions. RESULTS: Of the 17 patients, 6 were in the active stage and 11 were in the inactive stage according to the level of disease activity as clinically assessed by the NIH criteria. No significant 18F-FDG accumulation was observed in the patients with inactive disease (SUV≤1.2). 18F-FDG-PET/CT localised 18F-FDG accumulation in the inflammatory lesion in the patients with TAK who had inactive disease (n=3) assessed by the NIH criteria. 18F-FDG PET/CT revealed intense 18F-FDG accumulation (SUV max 2.88) in the vasculature of 3 patients in the inactive stage of TAK. The other 8 patients in the active stage showed weak 18F-FDG accumulation (SUV ≤1.2). CONCLUSION: 18FDG-PET/CT appears to be a promising technique for the diagnosis and assessment of disease activity in patients of TAK, even those considered to be inactive by the NIH criteria. However, it needs to be validated in larger groups for cost-effectiveness and sensitivity to change.


Assuntos
Aortite/diagnóstico por imagem , Arterite de Takayasu/diagnóstico por imagem , Adulto , Aortite/etiologia , Cegueira/etiologia , Sedimentação Sanguínea , Proteína C-Reativa/imunologia , Tontura/etiologia , Fadiga/etiologia , Feminino , Fluordesoxiglucose F18 , Humanos , Masculino , National Institutes of Health (U.S.) , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos , Arterite de Takayasu/complicações , Arterite de Takayasu/imunologia , Estados Unidos , Adulto Jovem
10.
Ann Rheum Dis ; 77(4): 589-595, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29374629

RESUMO

OBJETIVE: Systemic vasculitides represent a heterogeneous group of rare complex diseases of the blood vessels with a poorly understood aetiology. To investigate the shared genetic component underlying their predisposition, we performed the first cross-phenotype meta-analysis of genetic data from different clinically distinct patterns of vasculitis. METHODS: Immunochip genotyping data from 2465 patients diagnosed with giant cell arteritis, Takayasu's arteritis, antineutrophil cytoplasmic antibody-associated vasculitis or IgA vasculitis as well as 4632 unaffected controls were analysed to identify common susceptibility loci for vasculitis development. The possible functional consequences of the associated variants were interrogated using publicly available annotation data. RESULTS: The strongest association signal corresponded with an intergenic polymorphism located between HLA-DQB1 and HLA-DQA2 (rs6932517, P=4.16E-14, OR=0.74). This single nucleotide polymorphism is in moderate linkage disequilibrium with the disease-specific human leucocyte antigen (HLA) class II associations of each type of vasculitis and could mark them. Outside the HLA region, we identified the KDM4C gene as a common risk locus for vasculitides (highest peak rs16925200, P=6.23E-07, OR=1.75). This gene encodes a histone demethylase involved in the epigenetic control of gene expression. CONCLUSIONS: Through a combined analysis of Immunochip data, we have identified KDM4C as a new risk gene shared between systemic vasculitides, consistent with the increasing evidences of the crucial role that the epigenetic mechanisms have in the development of complex immune-mediated conditions.


Assuntos
Loci Gênicos/genética , Histona Desmetilases com o Domínio Jumonji/genética , Fenótipo , Vasculite Sistêmica/genética , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/genética , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/imunologia , Estudos de Casos e Controles , Epigênese Genética , Feminino , Loci Gênicos/imunologia , Predisposição Genética para Doença , Arterite de Células Gigantes/genética , Arterite de Células Gigantes/imunologia , Antígenos HLA-DQ/genética , Antígenos HLA-DQ/imunologia , Cadeias beta de HLA-DQ/genética , Cadeias beta de HLA-DQ/imunologia , Humanos , Histona Desmetilases com o Domínio Jumonji/imunologia , Desequilíbrio de Ligação , Masculino , Polimorfismo de Nucleotídeo Único , Análise Serial de Proteínas , Vasculite Sistêmica/imunologia , Arterite de Takayasu/genética , Arterite de Takayasu/imunologia
11.
Int J Rheum Dis ; 21(3): 740-745, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28791773

RESUMO

OBJECTIVE: To describe the features of exceptional coexisting Takayasu arteritis (TA) and sarcoidosis, two conditions of unknown cause associated with a common immunologic pattern. METHODS: We report seven cases of concomitant sarcoidosis-Takayasu or Takayasu-like vasculitis, observed in two referral centers between 1995 and 2015. RESULTS: All patients were female. The mean age at sarcoidosis diagnosis and TA diagnosis was 36 and 37 years, respectively. Sarcoidosis occurred in 86% of cases before or together with TA. Sarcoidosis always had a classic expression except for one renal localization. Sarcoidosis was not severe and mostly non-treated (86%). In all cases of TA, supra-aortic arteries were involved; in only two TA cases a more diffuse inflammatory arterial involvement was noted. In one case, Takayasu arteritis occurred despite immunosuppressive therapy given for sarcoidosis. All patients received for TA a treatment with corticosteroids associated with methotrexate (four cases), infliximab (one case) or tocilizumab (one case). After a mean follow-up of 89 months, TA always improved and no death was observed. CONCLUSIONS: TA stands as pathology associated with sarcoidosis. TA occurred in three cases among 50. When sarcoidosis preceded TA, a recovery of sarcoidosis was achieved mostly without treatment. TA is a prognostic and therapeutic factor. Immunosuppressive treatment, including steroids, led to a good prognosis for TA as well as for sarcoidosis.


Assuntos
Granuloma/complicações , Sarcoidose/complicações , Arterite de Takayasu/complicações , Adulto , Feminino , França , Granuloma/diagnóstico , Granuloma/tratamento farmacológico , Granuloma/imunologia , Humanos , Imunossupressores/uso terapêutico , Pessoa de Meia-Idade , Indução de Remissão , Sarcoidose/diagnóstico , Sarcoidose/tratamento farmacológico , Sarcoidose/imunologia , Arterite de Takayasu/diagnóstico , Arterite de Takayasu/tratamento farmacológico , Arterite de Takayasu/imunologia , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
12.
Clin Exp Rheumatol ; 36(1): 62-72, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-28770707

RESUMO

OBJECTIVES: This study aimed to clarify potential mechanism of IL-6 involved in adventitial fibrosis via adventitial fibroblast in Takayasu arteritis (TAK). METHODS: Immunohistochemistry and double-labelled immunofluorescence were performed on vascular tissue from patients with TAK and controls. Human aorta adventitial fibroblast (AAF) was cultured and stimulated with interleukine 6 (IL-6)/IL-6 receptor (IL-6R). Real-time PCR, western blot, enzyme-linked immunosorbent assays, chromatin immunoprecipitation (ChIP) and reporter assay were conducted in vitro experiments to determine effect of IL-6/IL-6R on AAF. RESULTS: The expression of IL-6, IL-6R, collagen I, collagen III, fibronectin, α-smooth muscle actin (α-SMA), and transforming growth factor (TGF-ß) in TAK arteries was significantly higher than that in the normal arteries. Co-localisation of α-SMA and IL-6 and a positive correlation between their expression were observed in local lesions. In vitro experiments, collagen I, collagen III, fibronectin, α-SMA, and TGF-ß expression increased significantly after stimulation and this fibrogenesis of AAFs was induced in TGF-ß-dependent and -independent manners. Additionally, phosphorylation of JAK2, STAT3 and Akt was significantly enhanced both in IL-6/IL-6R-treated AAFs in vitro and in TAK adventitial α-SMA positive cells. When AAFs were pretreated with inhibitors against JAK2, STAT3, and Akt, fibrosis was significantly reduced. Furthermore, IL-6/IL-6R promoted mRNA expression of IL-6 and MCP-1 in AAFs. Finally, according to ChIP and reporter assay results, STAT3 was the main transcriptional factor in the fibrosis of AAFs induced by IL-6/IL-6R. CONCLUSIONS: IL-6/IL-6R induces fibrogenesis of AAFs via the JAK2/STAT3 and JAK2/Akt pathways, which provides theoretical evidence for IL-6 as a treatment target in TAK.


Assuntos
Túnica Adventícia/metabolismo , Aorta/patologia , Fibroblastos/metabolismo , Interleucina-6/metabolismo , Arterite de Takayasu/metabolismo , Actinas/metabolismo , Adulto , Túnica Adventícia/efeitos dos fármacos , Túnica Adventícia/imunologia , Túnica Adventícia/patologia , Anti-Inflamatórios/uso terapêutico , Aorta/efeitos dos fármacos , Aorta/imunologia , Aorta/metabolismo , Estudos de Casos e Controles , Células Cultivadas , Feminino , Colágenos Fibrilares/genética , Colágenos Fibrilares/metabolismo , Fibroblastos/efeitos dos fármacos , Fibroblastos/imunologia , Fibroblastos/patologia , Fibrose , Humanos , Interleucina-6/antagonistas & inibidores , Interleucina-6/genética , Interleucina-6/imunologia , Janus Quinase 2/metabolismo , Masculino , Pessoa de Meia-Idade , Fosforilação , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptores de Interleucina-6/metabolismo , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais , Arterite de Takayasu/tratamento farmacológico , Arterite de Takayasu/imunologia , Arterite de Takayasu/patologia , Fator de Crescimento Transformador beta/metabolismo , Adulto Jovem
13.
Int J Rheum Dis ; 21(1): 271-277, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28261975

RESUMO

AIM: Takayasu arteritis (TA) is a rare autoimmune disease with ethnic differences. Genome-wide association studies (GWAS) showed novel genetic variants in the human leukocyte antigen (HLA) region were associated with TA. The present study aimed to investigate the linkage between these single nucleotide polymorphisms (SNP) and TA in a Chinese Han population. METHODS: Four hundred and twelve patients from multiple centers and 597 healthy controls were genotyped using the Sequenom MassArray iPLEX platform. The association between these SNPs and various clinical symptom of TA was also investigated. RESULTS: Our study showed a higher risk allele frequency of rs12524487 in TA patients compared to healthy controls (26.6% vs. 21.7%, odds ratio [OR] 1.31, 95% CI 1.06-1.61). The other SNP rs9366782 in HLA-B/MICA (major histocompatibility complex class I polypeptide-related sequence A) showed association with TA ischemic brain disease (OR: 1.78, 95% CI: 1.16-2.73, Pc = 0.03). However, rs3763288 and rs114202986 in MICA were negatively related to TA either as a whole or in any clinical features. Meanwhile, ATGT(rs9366782, rs12524487, rs3763288 and rs114202986) were the risk haplotypes (Pc = 2.48 × 10-10 ). CONCLUSIONS: Our findings indicated that rs12524487 in HLA-B/MICA was a genetic risk factor for TA in a Chinese Han population and rs9366782 in this region was associated with ischemic brain disease in TA but not TA susceptibility.


Assuntos
Antígenos HLA-B/genética , Antígenos de Histocompatibilidade Classe I/genética , Polimorfismo de Nucleotídeo Único , Arterite de Takayasu/genética , Adulto , Grupo com Ancestrais do Continente Asiático/genética , Isquemia Encefálica/diagnóstico , Isquemia Encefálica/etnologia , Isquemia Encefálica/genética , Isquemia Encefálica/imunologia , Estudos de Casos e Controles , Distribuição de Qui-Quadrado , China/epidemiologia , Feminino , Frequência do Gene , Estudos de Associação Genética , Predisposição Genética para Doença , Antígenos HLA-B/imunologia , Haplótipos , Antígenos de Histocompatibilidade Classe I/imunologia , Humanos , Desequilíbrio de Ligação , Masculino , Pessoa de Meia-Idade , Razão de Chances , Fenótipo , Fatores de Risco , Arterite de Takayasu/diagnóstico , Arterite de Takayasu/etnologia , Arterite de Takayasu/imunologia , Adulto Jovem
14.
Vasa ; 47(2): 149-152, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29271720

RESUMO

Takayasu arteritis (TA) is a rare large vessel vasculitis, affecting the aorta and its major branches, typically in young women. In this case report, we present three cases of young women of Caucasian descent who experienced relapses while under treatment with the monoclonal humanized antibody to the interleukin 6 receptor, tocilizumab. Active vasculitic lesions of the supraaortic (common carotid and axillary) arteries were detected and characterized via high resolution contrast enhanced ultrasound. Based on these cases, we discuss the potential role of contrast enhanced ultrasound in the diagnosis and follow-up of TA as well as the current data on the efficacy of tocilizumab in the treatment of TA.


Assuntos
Anti-Inflamatórios/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Artéria Axilar/diagnóstico por imagem , Artéria Carótida Primitiva/diagnóstico por imagem , Meios de Contraste/administração & dosagem , Fosfolipídeos/administração & dosagem , Hexafluoreto de Enxofre/administração & dosagem , Arterite de Takayasu/diagnóstico por imagem , Arterite de Takayasu/tratamento farmacológico , Ultrassonografia Doppler em Cores , Adulto , Feminino , Humanos , Valor Preditivo dos Testes , Recidiva , Arterite de Takayasu/imunologia , Resultado do Tratamento , Adulto Jovem
15.
J Vasc Surg ; 67(5): 1501-1511, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29242069

RESUMO

OBJECTIVE: The objective of this study was to describe large-vessel vasculitis (LVV) in patients with human immunodeficiency virus (HIV) infection. It is a retrospective single-center study conducted between 2000 and 2015 through a university hospital of 11 HIV-infected patients with LVV. METHODS: The characteristics and outcome of 11 HIV-infected patients with LVV (7 patients fulfilled international criteria for Takayasu arteritis, 5 patients had histologic findings of vasculitis, and 5 patients had imaging features of aortitis) were analyzed and compared with those of 82 patients with LVV but without HIV infection. RESULTS: Concerning the HIV-infected patients with LVV (n = 11), the mean age was 40 years (range, 36-56 years), and 55% of patients were female. At diagnosis of LLV, the mean initial CD4 cell count was 455 cells/mm3 (range, 166-837 cells/mm3), and the median HIV viral load was 9241 copies. Vascular lesions were located in the aorta (n = 7), in supra-aortic trunks (n = 7), and in digestive arteries (n = 3). Inflammatory aorta infiltrates showed a strong expression of interferon-γ and interleukin 6. In HIV-negative LVV patients (n = 82), the median age was 42 years, and 88% of the patients were women. Thirty patients had an inflammatory syndrome. Seventy patients had been treated with glucocorticosteroids and 57 with immunosuppressive treatments. Compared with their negative counterparts, HIV-positive patients with LVV were more frequently male (P = .014), had more vascular complications (ie, Ishikawa score; P = .017), and had more frequent revascularization (P = .047). After a mean follow-up of 96 months, four relapses of vasculitis were reported, and one patient died. Regardless of the HIV virologic response, antiretroviral therapy improved LVV in only one case. CONCLUSIONS: LVV in HIV-infected patients is a rare and severe entity.


Assuntos
Aortite , Infecções por HIV , Arterite de Takayasu , Adulto , Antivirais/uso terapêutico , Aortite/tratamento farmacológico , Aortite/epidemiologia , Aortite/imunologia , Aortite/virologia , Contagem de Linfócito CD4 , Feminino , Glucocorticoides/uso terapêutico , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Infecções por HIV/imunologia , Infecções por HIV/virologia , Humanos , Imunossupressores/uso terapêutico , Masculino , Pessoa de Meia-Idade , Paris/epidemiologia , Recidiva , Estudos Retrospectivos , Arterite de Takayasu/tratamento farmacológico , Arterite de Takayasu/epidemiologia , Arterite de Takayasu/imunologia , Arterite de Takayasu/virologia , Fatores de Tempo , Resultado do Tratamento , Carga Viral , Adulto Jovem
16.
Presse Med ; 46(7-8 Pt 2): e189-e196, 2017.
Artigo em Francês | MEDLINE | ID: mdl-28803683

RESUMO

Takayasu arteritis (TAK) is a vasculitis of the large arteries. The arterial wall, target of the immune reaction, is composed of vascular dendritic cells, endothelial cells, vascular smooth muscle cells and fibroblasts, which engage in an interaction with T cells and macrophages to, ultimately, cause luminal stenosis or aneurysmal wall damage of the vessel. A multitude of cytokines have been identified to increase in case of TAK and to be linked to disease activity. A better understanding of the physiopathological pathways and mechanisms involved, might enable a more tailored therapeutic approach in TAK.


Assuntos
Arterite de Takayasu/imunologia , Proteínas 14-3-3/metabolismo , Anticorpos/análise , Anticorpos Antifosfolipídeos/análise , Apoptose , Linfócitos B/metabolismo , Diferenciação Celular , Células Endoteliais/imunologia , Proteínas de Choque Térmico/metabolismo , Humanos , Imunidade Inata , Interferon gama/metabolismo , Interleucinas/metabolismo , Mycobacterium tuberculosis , Receptores de Antígenos de Linfócitos T/metabolismo , Células Th17/citologia
17.
Autoimmun Rev ; 16(10): 1071-1078, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28778711

RESUMO

There is a growing need for disease related biomarkers in Takayasu arteritis (TA).The assessment of pro-inflammatory cytokines and chemokines in TA may provide a better understanding of its pathophysiology, and circulating levels of these mediators may act as biomarkers of disease activity. Serum level of interleukin 6 (IL-6) is a potential biomarker for TA, which is mostly associated with TA status and disease activity. Associations between TA and serum/plasma levels of other cytokines are less clear. mRNA expression of IL-4 and tumor necrosis factor α (TNFα) are constitutively increased in peripheral blood mononuclear cells (PBMC) from TA patients and the expression of both cytokines increases even more after PBMC stimulation in vitro, while the expression of IL-10 mRNA decreases. In addition, circulating T cells from TA patients produce increased levels of both Th1- and Th17-related cytokines upon in vitro stimulation. In the aorta from TA patients, an increased expression of interferon γ (IFNγ), IL-6, IL-12 and IL-17 has been described. Regarding circulating chemokines in TA, serum/plasma levels of IL-8 (CXCL8), CCL2 and CCL5 were shown to be elevated in TA patients compared with healthy controls as well as in TA patients with active disease compared with those in remission. Serum IL-6 seems to be the best biomarker for disease state and disease activity in TA and increased Th1 and Th17 responses are predominant in the pathophysiology of TA.


Assuntos
Biomarcadores/sangue , Quimiocinas/imunologia , Citocinas/imunologia , Arterite de Takayasu/imunologia , Humanos
18.
Z Rheumatol ; 76(6): 509-523, 2017 Aug.
Artigo em Alemão | MEDLINE | ID: mdl-28638968

RESUMO

According to the Chapel Hill Classification, large vessel vasculitides encompass giant cell arteritis (GCA) and the histologically related Takakaysu arteritis (TAK). The two diseases lack autoantibodies and present with a systemic inflammatory response. GCA typically shows a sudden onset with profound sickness, loss of appetite and of body weight, and temporal headache. Due to the substantial risk of sudden blindness, diagnostic work-up has to be performed immediately and treatment started without delay. A close association between polymyalgia rheumatica (PMR) and GCA is well established. Takayasu arteritis very often begins in adolescence. In contrast to GCA, the general symptoms are much less pronounced and aside from occasional carotidodynia there is a lack of diagnostic symptoms. TAK is often diagnosed in late stages due to exercise-induced claudication.


Assuntos
Arterite de Células Gigantes , Polimialgia Reumática , Arterite de Takayasu , Adolescente , Arterite de Células Gigantes/imunologia , Arterite de Células Gigantes/terapia , Humanos , Polimialgia Reumática/imunologia , Polimialgia Reumática/terapia , Arterite de Takayasu/imunologia , Arterite de Takayasu/terapia
19.
BMJ Open ; 7(4): e014451, 2017 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-28473512

RESUMO

BACKGROUND: Platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR) have been reported to reflect the inflammatory response and disease activity in a variety of autoimmune diseases. OBJECTIVES: This study aimed to evaluate the value of PLR and NLR as markers to monitor disease activity in Takayasu's arteritis (TAK). METHODS: A retrospective case-control study involving 88 patients with TAK and 78 healthy controls was performed. We compared the PLR and NLR between patients and healthy controls, and also analysed the correlations between PLR or NLR and indices of TAK disease activity. RESULTS: Increased PLR and NLR were observed in patients with TAK. PLR was positively correlated with hs-C-reactive protein (hs-CRP) (r=0.239, p=0.010) and erythrocyte sedimentation rate (ESR) (r=0.270, p=0.010). NLR also exhibited a positive relationship with Kerr's score (r=0.284, p=0.002), hs-CRP (r=0.313, p=0.006) and ESR (r=0.249, p=0.019). A PLR level of 183.39 was shown to be the predictive cut-off value for TAK (sensitivity 37.8%, specificity 93.0%, area under the curve (AUC)=0.691). A NLR level of 2.417 was found to be the predictive cut-off value for TAK (sensitivity 75.6%, specificity 55.8%, AUC=0.697). CONCLUSIONS: PLR and NLR could be useful markers to reflect inflammation and disease activity in patients with TAK.


Assuntos
Plaquetas/citologia , Contagem de Células , Linfócitos/citologia , Neutrófilos/citologia , Arterite de Takayasu/sangue , Arterite de Takayasu/imunologia , Adolescente , Adulto , Biomarcadores/sangue , Estudos de Casos e Controles , Feminino , Humanos , Inflamação/sangue , Inflamação/imunologia , Contagem de Linfócitos , Linfócitos/imunologia , Masculino , Pessoa de Meia-Idade , Neutrófilos/imunologia , Valor Preditivo dos Testes , Curva ROC , Estudos Retrospectivos , Adulto Jovem
20.
Clin Exp Rheumatol ; 35 Suppl 103(1): 102-110, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28466804

RESUMO

OBJECTIVES: To investigate serum levels of IL- 6 and soluble IL-6 receptor (sIL-6R) in patients with large-vessel vasculitis and their relationship with disease activity. METHODS: Sera were obtained from 33 Takayasu's arteritis (TAK) patients and 14 giant cell arteritis (GCA) patients, and from 60 age-matched normal controls (NCs). Disease activity was assessed using 18F-FDG PET/CT and clinical indices including NIH/Kerr criteria and ITAS. Among TAK patients with active disease at baseline, clinical records and serum samples from 11 TAK patients were available for the longitudinal study. IL-6 and sIL-6R serum levels were evaluated using commercial ELISA kits. RESULTS: IL-6 and sIL-6R serum levels were significantly higher in both GCA and TAK patients compared to NCs. IL-6 levels in TAK patients were significantly increased irrespective of disease phase, while a significant increase in sIL-6R concentrations was only found in TAK patients with active disease. Conversely, in GCA, IL-6 levels were significantly raised only in patients with active diseases, whereas sIL-6R levels appeared to be significantly higher irrespective of disease activity. Longitudinal analysis showed that levels of sIL-6R in TAK patients were significantly higher only at baseline, compared to NCs, whereas IL-6 levels were found to be significantly increased at each follow-up time point. CONCLUSIONS: These overall results might suggest a role for sIL-6R as a potential biomarker for disease activity in TAK patients, whereas in GCA, modifications of IL-6 might better identify patients with active disease.


Assuntos
Arterite de Células Gigantes/sangue , Interleucina-6/sangue , Receptores de Interleucina-6/sangue , Arterite de Takayasu/sangue , Idoso , Biomarcadores/sangue , Estudos de Casos e Controles , Análise por Conglomerados , Estudos Transversais , Ensaio de Imunoadsorção Enzimática , Feminino , Fluordesoxiglucose F18/administração & dosagem , Arterite de Células Gigantes/diagnóstico por imagem , Arterite de Células Gigantes/imunologia , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Valor Preditivo dos Testes , Prognóstico , Compostos Radiofarmacêuticos/administração & dosagem , Índice de Gravidade de Doença , Arterite de Takayasu/diagnóstico por imagem , Arterite de Takayasu/imunologia , Fatores de Tempo , Regulação para Cima
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