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1.
Ann Rheum Dis ; 81(3): 386-397, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34844932

RESUMO

OBJECTIVES: Behçet's syndrome (BS) is a rare systemic vasculitis often complicated by thrombotic events. Given the lack of validated biomarkers, BS diagnosis relies on clinical criteria.In search of novel biomarkers for BS diagnosis, we determined the profile of plasmatic circulating microRNAs (ci-miRNAs) in patients with BS compared with healthy controls (HCs). METHODS: ci-miRNA profile was evaluated by microarray in a screening cohort (16 patients with BS and 18 HCs) and then validated by poly(T) adaptor PCR (PTA-PCR) in a validation cohort (30 patients with BS and 30 HCs). Two disease control groups (30 patients with systemic lupus erythematosus (SLE) and 30 patients with giant cell arteritis (GCA) were also analysed. RESULTS: From the microarray screening, 29 deregulated (differentially expressed (DE)) human ci-miRNAs emerged. A hierarchical cluster analysis indicated that DE ci-miRNAs clearly segregated patients from controls, independently of clinical features. PTA-PCR analysis on the validation cohort confirmed the deregulation of miR-224-5p, miR-206 and miR-653-5p. The combined receiver operating characteristic (ROC) curve analyses showed that such ci-miRNAs discriminate BS from HCs (and BS with active vs inactive disease), as well as BS from patients with SLE and GCA.The functional annotation analyses (FAAs) showed that the most enriched pathways affected by DE ci-miRNAs (ie, cell-matrix interaction, oxidative stress and blood coagulation) are related to thrombo-inflammatory mechanisms. Accordingly, the expression of the three ci-miRNAs from the validation cohort significantly correlated with leucocyte reactive oxygen species production and plasma lipid peroxidation. CONCLUSIONS: The ci-miRNA profile identified in this study may represent a novel, poorly invasive BS biomarker, while suggesting an epigenetic control of BS-related thrombo-inflammation.


Assuntos
Síndrome de Behçet/genética , MicroRNA Circulante/sangue , Tromboinflamação/genética , Adulto , Síndrome de Behçet/sangue , Biomarcadores/sangue , Estudos de Casos e Controles , Feminino , Perfilação da Expressão Gênica , Arterite de Células Gigantes/sangue , Arterite de Células Gigantes/genética , Humanos , Lúpus Eritematoso Sistêmico/sangue , Lúpus Eritematoso Sistêmico/genética , Masculino , MicroRNAs/sangue , Reação em Cadeia da Polimerase , Estudos Prospectivos , Curva ROC , Tromboinflamação/sangue
3.
J Autoimmun ; 121: 102652, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34000675

RESUMO

This study aimed to assess the implication of mucosal-associated invariant T (MAIT) cells in GCA. Blood samples were obtained from 34 GCA patients (before and after 3 months of treatment with glucocorticoids (GC) alone) and compared with 20 controls aged >50 years. MAIT cells, defined by a CD3+CD4-TCRγδ-TCRVα7.2+CD161+ phenotype, were analyzed by flow cytometry. After sorting, we assessed the ability of MAIT cells to proliferate and produce cytokines after stimulation with anti CD3/CD28 microbeads or IL-12 and IL-18. MAIT were stained in temporal artery biopsies (TAB) by confocal microscopy. MAIT cells were found in the arterial wall of positive TABs but was absent in negative TAB. MAIT frequency among total αß-T cells was similar in the blood of patients and controls (0.52 vs. 0.57%; P = 0.43) and not modified after GC treatment (P = 0.82). Expression of IFN-γ was increased in MAIT cells from GCA patients compared to controls (44.49 vs. 32.9%; P = 0.029), and not modified after 3 months of GC therapy (P = 0.82). When they were stimulated with IL-12 and IL-18, MAIT from GCA patients produced very high levels of IFN-γ and displayed a stronger proliferation compared with MAIT from controls (proliferation index 3.39 vs. 1.4; P = 0.032). In GCA, the functional characteristics of MAIT cells are modified toward a pro-inflammatory phenotype and a stronger proliferation capability in response to IL-12 and IL-18, suggesting that MAIT might play a role in GCA pathogenesis. Our results support the use of treatments targeting IL-12/IL-18 to inhibit the IFN-γ pathway in GCA.


Assuntos
Arterite de Células Gigantes/imunologia , Células T Invariantes Associadas à Mucosa/imunologia , Idoso , Biópsia , Estudos de Casos e Controles , Proliferação de Células , Células Cultivadas , Feminino , Arterite de Células Gigantes/sangue , Arterite de Células Gigantes/patologia , Voluntários Saudáveis , Humanos , Interferon gama/metabolismo , Interleucina-12/metabolismo , Interleucina-18/metabolismo , Masculino , Pessoa de Meia-Idade , Células T Invariantes Associadas à Mucosa/metabolismo , Cultura Primária de Células , Estudos Prospectivos , Transdução de Sinais/imunologia , Artérias Temporais/patologia , Técnicas de Cultura de Tecidos
4.
Ann Neurol ; 90(1): 118-129, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33993547

RESUMO

OBJECTIVE: The objective of this study was to characterize patients with extracranial giant cell arteritis with intracranial involvement. METHODS: In a multicenter retrospective study, we included 31 patients with systemic giant cell arteritis (GCA) with intracranial involvement. Clinical characteristics, pattern of arterial involvement, and cytokine profiles were assessed. Patients with GCA without intracranial involvement (n = 17), and with intracranial atherosclerosis (n = 25) served as controls. RESULTS: Erythrocyte sedimentation rate (ESR) was elevated in 18 patients (69.2%) with and in 16 patients (100%) without intracranial involvement (p = 0.02). Headache was complained by 15 patients (50.0%) with and 13 patients (76.5%) without intracranial involvement (p = 0.03). Posterior circulation arteries were affected in 26 patients (83.9%), anterior circulation arteries in 17 patients (54.8%), and both territories in 12 patients (38.7%). Patients with GCA had vertebral artery stenosis proximal and, in contrast, patients with atherosclerosis distal to the origin of posterior inferior cerebellar artery (PICA). Among patients with GCA with intracranial involvement, 11 patients (37.9%) had a rapid progressive disease course characterized by short-term recurrent ischemic events. The median modified Rankin Scale (mRS) at follow-up in these patients was 4 (interquartile range [IQR] = 2.0-6.0) and 4 patients (36.4%) died. Vessel wall expression of IL-6 and IL-17 was significantly increased in patients with rapid progressive course. INTERPRETATION: Typical characteristics of GCA, headache, and an elevated ESR, are frequently absent in patients with intracranial involvement. However, differentiation of intracranial GCA from atherosclerosis can be facilitated by the typical pattern of vertebral artery stenosis. About one-third of patients with intracranial GCA had a rapid progressive course with poor outcome. IL-17 and IL-6 may represent potential future treatment targets. ANN NEUROL 2021;90:118-129.


Assuntos
Sedimentação Sanguínea , Arterite de Células Gigantes/sangue , Idoso , Idoso de 80 Anos ou mais , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
6.
Int J Rheum Dis ; 24(6): 781-788, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33847438

RESUMO

AIM: Diagnosing and monitoring vascular activity in giant cell arteritis (GCA) is difficult due to the paucity of specific serological biomarkers. We assessed the utility of 8 novel biomarkers in an inception cohort of newly suspected GCA patients. METHOD: Consecutive patients were enrolled between May 2016 and December 2017. Serum was collected within 72 hours of commencing corticosteroids and at 6 months. It was analyzed for levels of intra-cellular adhesion molecule 1, vascular endothelial growth factor (VEGF), pentraxin 3, von Willebrand factor and procalcitonin (5-plex R&D Systems multiplex assay) and interleukin (IL)6, IL12 and interferon-γ (high-sensitivity 3-plex ProcartaPlex multiplex assay). A GCA specific positron emission tomography / computed tomography (PET/CT) scan was performed at enrolment with uptake in each vascular territory graded and summed to derive a total vascular score (TVS). RESULTS: For the 63 patients enrolled, 12 (19%) had a final diagnosis of biopsy-positive GCA and a further 9 had a clinical diagnosis of biopsy-negative GCA. None of the 8 biomarkers was significantly higher in GCA patients compared with those with alternative diagnoses, or demonstrated a positive correlation with the PET/CT TVS. This was in contrast to the C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) which were higher in the biopsy-positive GCA cohort (P < .04) and showed weak positive correlations with the TVS (correlation coefficient 0.34, P < .01). Procalcitonin did not distinguish between GCA and infection. Concentrations of CRP, ESR, VEGF and pentraxin 3 decreased between diagnosis and 6 months in GCA patients. CONCLUSION: This study did not identify new serological biomarkers to assist in diagnosing or assessing the vasculitis burden in GCA.


Assuntos
Biomarcadores/sangue , Arterite de Células Gigantes/diagnóstico , Corticosteroides/uso terapêutico , Idoso , Biópsia , Proteína C-Reativa , Ensaio de Imunoadsorção Enzimática , Fluordesoxiglucose F18/metabolismo , Arterite de Células Gigantes/sangue , Arterite de Células Gigantes/tratamento farmacológico , Arterite de Células Gigantes/patologia , Humanos , Interferon gama , Interleucina-12 , Interleucina-6/sangue , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Pró-Calcitonina/metabolismo , Sensibilidade e Especificidade , Componente Amiloide P Sérico , Fator A de Crescimento do Endotélio Vascular/sangue , Fator de von Willebrand/metabolismo
7.
Sci Rep ; 11(1): 6220, 2021 03 18.
Artigo em Inglês | MEDLINE | ID: mdl-33737697

RESUMO

Identifying comorbidities in polymyalgia rheumatica/giant cell arteritis (PMR/GCA) is crucial for patients' outcomes. The present study aimed to evaluate the impact of the inflammatory process and glucocorticoid treatment on aortic arterial stiffness and body composition in PMR/GCA. 77 patients with newly diagnosed PMR/GCA were treated with oral glucocorticoids and followed for 40 weeks. Aortic pulse wave velocity (PWV) was measured at baseline and during the follow-up period and compared to the results of temporal artery biopsy (TAB) and 18F-FDG PET/CT. Body composition was assessed by total body DXA at baseline and the end of the study. Of 77 patients (49 (63.6%) female, mean of age: (71.8 ± 8.0)), 64 (83.1%) had pure PMR, 10 (13.0%) concomitant PMR and GCA, and 3 (3.9%) pure GCA. Compared to baseline values, aortic PWV was initially decreased at week 16 (p = 0.010) and remained lower than baseline at week 28 (p = 0.002) and week 40 (p < 0.001), with no association with results of TAB and 18F-FDG PET/CT. Aortic PWV was significantly associated with age, male gender, left systolic and diastolic blood pressure, right diastolic blood pressure, and CRP. Total bone mineral content (BMC) was decreased in both genders (p < 0.001), while fat mass (FM) was significantly increased (p < 0.001). However, lean body mass did not significantly change during the study. Changes in FM were correlated with cumulative prednisolone dose (rho: 0.26, p = 0.031). Glucocorticoid treatment of patients with PMR/GCA had several prognostic impacts. Arterial stiffness was decreased due either to the treatment or a reduction in the inflammatory load. Additionally, treatment led to changes in body composition, including a decrease in BMC and FM excess.


Assuntos
Aorta/efeitos dos fármacos , Arterite de Células Gigantes/tratamento farmacológico , Glucocorticoides/uso terapêutico , Polimialgia Reumática/tratamento farmacológico , Prednisolona/uso terapêutico , Tecido Adiposo Branco/diagnóstico por imagem , Tecido Adiposo Branco/efeitos dos fármacos , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Aorta/metabolismo , Biópsia , Pressão Sanguínea/efeitos dos fármacos , Composição Corporal/efeitos dos fármacos , Densidade Óssea/efeitos dos fármacos , Proteína C-Reativa/metabolismo , Feminino , Fluordesoxiglucose F18/metabolismo , Arterite de Células Gigantes/sangue , Arterite de Células Gigantes/diagnóstico por imagem , Arterite de Células Gigantes/patologia , Humanos , Estudos Longitudinais , Masculino , Polimialgia Reumática/sangue , Polimialgia Reumática/diagnóstico por imagem , Polimialgia Reumática/patologia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Prognóstico , Análise de Onda de Pulso , Fatores Sexuais , Artérias Temporais/efeitos dos fármacos , Artérias Temporais/metabolismo , Rigidez Vascular/efeitos dos fármacos
8.
Int J Med Sci ; 18(7): 1532-1540, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33746569

RESUMO

Background: Neutrophil extracellular traps (NETs) have been implicated in host immune responses. Attempts have been made to examine how NETs affect the pathogenesis of complications such as autoimmune and vascular disorders. Aim: This study aimed to explore the relationship between NETs and vasculitis. Material and Methods: The current study entailed the searching of PsycINFO, PubMed, Web of Science, and CINAHL for articles related to the research topic. The search terms and phrases included "vasculitis," "NETs," "neutrophil extracellular traps," "NETosis," and "pathogenesis." The search was limited to articles published between 2009 and 2019. Results: Researchers have shown that NETs contribute to the pathogenesis of vasculitis through different mechanisms and processes, including renal failure and vascular damage. The protective effects of NETs have also been highlighted. Discussion: Overall, some scholars have shown the effectiveness of using DNase I and the PAD4 inhibitor Cl-amidine to treat vasculitis by restricting NET formation. However, observations have been noted in only animal experimental models. Conclusion: Neutrophil hyperactivity and its role in vasculitis are not yet fully understood. More studies aiming to determine the accurate function of NETs in vasculitis pathogenesis, particularly in humans, should be undertaken. Intensive research on NETs and vasculitis can increase the knowledge of medical practitioners and contribute to the development of new treatment methods to enhance patient outcomes in the future.


Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/imunologia , Armadilhas Extracelulares/imunologia , Arterite de Células Gigantes/imunologia , Neutrófilos/imunologia , Arterite de Takayasu/imunologia , Animais , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/sangue , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/tratamento farmacológico , Apoptose , Desoxirribonuclease I/farmacologia , Desoxirribonuclease I/uso terapêutico , Modelos Animais de Doenças , Armadilhas Extracelulares/efeitos dos fármacos , Arterite de Células Gigantes/sangue , Arterite de Células Gigantes/tratamento farmacológico , Humanos , Neutrófilos/citologia , Neutrófilos/efeitos dos fármacos , Neutrófilos/patologia , Ornitina/análogos & derivados , Ornitina/farmacologia , Ornitina/uso terapêutico , Proteína-Arginina Desiminase do Tipo 4/antagonistas & inibidores , Proteína-Arginina Desiminase do Tipo 4/metabolismo , Morte Celular Regulada/efeitos dos fármacos , Morte Celular Regulada/imunologia , Arterite de Takayasu/sangue , Arterite de Takayasu/tratamento farmacológico
9.
Curr Rheumatol Rep ; 23(3): 17, 2021 02 10.
Artigo em Inglês | MEDLINE | ID: mdl-33569633

RESUMO

PURPOSE OF REVIEW: Large vessel vasculitides (LVVs) are inflammatory conditions of the wall of large-sized arteries, mainly represented by giant cell arteritis (GCA) and Takayasu arteritis (TA). The inflammatory process within the vessel wall can lead to serious consequences such as development of aneurysms, strokes and blindness; therefore, early diagnosis and follow-up of LVV are fundamental. However, the arterial wall is poorly accessible and blood biomarkers are intended to help physicians not only in disease diagnosis but also in monitoring and defining the prognosis of these conditions, thus assisting therapeutic decisions and favouring personalised management. The field is the object of intense research as the identification of reliable biomarkers is likely to shed light on the mechanisms of disease progression and arterial remodelling. In this review, we will discuss the role of blood biomarkers in LVVs in the light of the latest evidence. RECENT FINDINGS: In clinical practice, the most widely performed laboratory investigations are the erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). However, these indices may be within normal limits during disease relapse and they are not reliable in patients receiving interleukin-6 (IL-6) receptor inhibitors. New biomarkers struggle to gain traction in clinical practice and no molecule with good accuracy has been identified to date. IL-6, a pro-inflammatory cytokine that drives CRP synthesis and increases the ESR, is one of the most promising biomarkers in the field. IL-6 analysis is increasingly performed, and serum levels are more sensitive than ESR for active GCA and might reflect persistent inflammation with high risk of relapse in patients on IL-6 receptor inhibitors. A future with biomarkers that reflect different disease features is an important aspiration. Accordingly, intense effort is being made to identify IL-6-independent inflammatory biomarkers, such as S100 proteins, pentraxin-3 and osteopontin. Moreover, metalloproteinases such as MMP2/9 and angiogenic modulators such as VEGF, YLK-40 and angiopoietins are being studied as markers of arterial remodelling. Lastly, biomarkers indicating organ damage may guide prognostic stratification as well as emergency therapeutic decisions: the most promising biomarkers so far identified are NT-proBNP, which reflects myocardial strain; pentraxin-3, which has been associated with recent optic nerve ischemia; and endothelin-1, which is associated with ischaemic complications. Currently, the use of these molecules in clinical practice is limited because of their restricted availability, lack of sufficient studies supporting their validity and associated costs. Further evidence is required to better interpret their biological and clinical value.


Assuntos
Arterite de Células Gigantes , Arterite de Takayasu , Biomarcadores/sangue , Citocinas/sangue , Arterite de Células Gigantes/sangue , Arterite de Células Gigantes/diagnóstico , Humanos , Prognóstico , Arterite de Takayasu/sangue , Arterite de Takayasu/diagnóstico , Vasculite/sangue , Vasculite/diagnóstico
10.
Medicine (Baltimore) ; 99(39): e22406, 2020 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-32991468

RESUMO

Giant cell arteritis (GCA) is the most common vasculitis in elderly, with ischemic and constitutional symptoms caused by vascular involvement and systemic inflammation. Early initiation of therapy results in prompt remission, while patients may still experience flares or severe complications during glucocorticoid tapering. This study was to identify the characteristics of Chinese GCA patients with different prognosis.Ninety-one patients diagnosed with GCA in Peking Union Medical College Hospital in the last 20 years were followed up. Those who were lost to follow up or were followed up for less than 1 year were excluded. According to the prognosis, patients were divided into the group of favourable prognosis (patients who sustained disease remission for over 1 year) and unfavorable prognosis (patients who had relapses or severe complications). Clinical data at disease onset and after treatment were collected and analysed between the 2 groups.Thirty-seven patients with favourable prognosis and 40 patients with unfavourable prognosis were admitted into the study. Fever as an onset symptom was less common in favourable group (P=.016). As for presentations of GCA, fever, tenderness and abnormal pulsation of temporal artery and jaw claudication were less frequently observed in patients with favourable prognosis (P=.029, .049, .043, respectively). At onset, medium-size arteries were affected more in unfavorable prognosis group (P = .048), and involvement of branches below the aortic arch were more common in favorable prognosis group (P = .034). Erythrocyte sedimentation rate in group of favourable prognosis were significantly lower after treatment (P = .041). Compared with healthy subjects, GCA patients had increased monocytes and decreased lymphocytes at disease onset (P < .01). Monocyte counts were higher in patients with favourable prognosis at disease onset (P = .043), while no significant differences were seen between the 2 groups after treatment. Lymphocyte counts were lower in patients with unfavourable prognosis (P = .014) after treatment.Complete blood count may reflect the disease status of GCA. Little change in monocyte during treatment and lower lymphocytes after treatment may serve as potential predictors of unfavourable clinical prognosis.


Assuntos
Arterite de Células Gigantes/sangue , Idoso , Contagem de Células Sanguíneas , Feminino , Arterite de Células Gigantes/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos
12.
Sci Rep ; 10(1): 6405, 2020 04 14.
Artigo em Inglês | MEDLINE | ID: mdl-32286393

RESUMO

The mechanisms regulating inflammation in large vessels vasculitis (LVV) are poorly understood. Interleukin 33 (IL-33) has been shown to license innate and adaptive immunity by enhancing Th2 cytokines production. We aimed to examine the role of IL-33 in the immunomodulation of T cell activation in LVV. T cell homeostasis and cytokines production were determined in peripheral blood from 52 patients with giant cell arteritis (GCA) and 50 healthy donors (HD), using Luminex assay, flow cytometry, quantitative RT-PCR and by immunofluorescence analysis in inflammatory aorta lesions. We found increased level of IL-33 and its receptor ST2/IL-1R4 in the serum of patient with LVV. Endothelial cells were the main source of IL-33, whereas Th2 cells, Tregs and mast cells (MC) express ST2 in LVV vessels. IL-33 had a direct immunomodulatory impact by increasing Th2 and Tregs. IL-33 and MC further enhanced Th2 and regulatory responses by inducing a 6.1 fold increased proportion of Tregs (p = 0.008). Stimulation of MC by IL-33 increased indoleamine 2 3-dioxygenase (IDO) activity and IL-2 secretion. IL-33 mRNA expression was significantly correlated with the expression of IL-10 and TGF-ß within aorta inflammatory lesions. To conclude, our findings suggest that IL-33 may exert a critical immunoregulatory role in promoting Tregs and Th2 cells in LVV.


Assuntos
Arterite de Células Gigantes/imunologia , Interleucina-33/imunologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Arterite de Células Gigantes/sangue , Arterite de Células Gigantes/patologia , Humanos , Inflamação/sangue , Inflamação/imunologia , Proteína 1 Semelhante a Receptor de Interleucina-1/metabolismo , Interleucina-33/sangue , Masculino , Mastócitos/imunologia , Células Th2/imunologia
13.
Rheumatology (Oxford) ; 59(11): 3229-3236, 2020 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-32240313

RESUMO

OBJECTIVES: To investigate metabolic features that may predispose to GCA in a nested case-control study. METHODS: Individuals who developed GCA after inclusion in a population-based health survey (the Malmö Preventive Medicine Project; N = 33 346) were identified and validated through a structured review of medical records. Four controls for every validated case were selected from the database. RESULTS: A total of 76 cases with a confirmed incident diagnosis of GCA (61% female, 65% biopsy positive, mean age at diagnosis 70 years) were identified. The median time from screening to diagnosis was 20.7 years (range 3.0-32.1). Cases had significantly lower fasting blood glucose (FBG) at baseline screening compared with controls [mean 4.7 vs 5.1 mmol/l (S.d. overall 1.5), odds ratio (OR) 0.35 per mmol/l (95% CI 0.17, 0.71)] and the association remained significant when adjusted for smoking [OR 0.33 per mmol/l (95% CI 0.16, 0.68)]. Current smokers had a reduced risk of GCA [OR 0.35 (95% CI 0.18, 0.70)]. Both cholesterol [mean 5.6 vs 6.0 mmol/l (S.d. overall 1.0)] and triglyceride levels [median 1.0 vs 1.2 mmol/l (S.d. overall 0.8)] were lower among the cases at baseline screening, with significant negative associations with subsequent GCA in crude and smoking-adjusted models [OR 0.62 per mmol/l (95% CI 0.43, 0.90) for cholesterol; 0.46 per mmol/l (95% CI 0.27, 0.81) for triglycerides]. CONCLUSION: Development of GCA was associated with lower FBG and lower cholesterol and triglyceride levels at baseline, all adjusted for current smoking, suggesting that metabolic features predispose to GCA.


Assuntos
Glicemia/análise , Colesterol/sangue , Jejum/sangue , Arterite de Células Gigantes/etiologia , Triglicerídeos/sangue , Idoso , Idoso de 80 Anos ou mais , Índice de Massa Corporal , Estudos de Casos e Controles , Intervalos de Confiança , Feminino , Arterite de Células Gigantes/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Fatores Sexuais , Fumantes , Fumar/sangue , Suécia
14.
Rheumatology (Oxford) ; 59(10): 2953-2959, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-32125431

RESUMO

OBJECTIVES: Vision complications and a stroke represent severe cranial ischaemic complications (sCIC) associated with increased morbidity and mortality in GCA. We aimed to determine the risk factors for sCIC in GCA. METHODS: We analysed the medical records of prospectively enrolled GCA patients diagnosed between September 2011 and August 2019, and compared the clinical and laboratory characteristics of patients with and without sCIC defined as either severe vision complications (diplopia, transient vision loss, permanent partial vision field/acuity defect and permanent visual loss) or stroke. RESULTS: During the 96-month observation period, we identified 295 new GCA patients [65.4% female, median (interquartile range) age 74.7 (67.3-80.0) years]. Sixty-one (20.7%) patients developed sCIC (52 isolated severe vision complications, 5 isolated ischaemic strokes and 4 patients with both complications). In a multivariable logistic regression model jaw claudication [odds ratio (OR) 3.43 (95% CI: 1.84, 6.42), P < 0.001], smoking [OR 1.92 (95% CI: 1.01, 3.65), P = 0.046] and increasing age [OR 1.08 (95% CI: 1.04, 1.13), P < 0.001] were significantly associated with sCIC. Higher CRP [OR 0.99 (0.99-1.00), P = 0.011] decreased the risk of sCIC. When considered separately, the odds for severe vision complications increased with age and jaw claudication, and decreased with polymyalgia rheumatica, constitutional symptoms and higher CRP. Atrial fibrillation emerged as the sole independent predictor of ischaemic stroke. CONCLUSION: Increasing age, jaw claudication and smoking predicted sCIC, while higher CRP decreased the risk of sCIC in our GCA cohort.


Assuntos
Isquemia Encefálica/complicações , Arterite de Células Gigantes/complicações , AVC Isquêmico/etiologia , Transtornos da Visão/etiologia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Anti-Inflamatórios não Esteroides/uso terapêutico , Aspirina , Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/epidemiologia , Proteína C-Reativa/metabolismo , Feminino , Arterite de Células Gigantes/sangue , Arterite de Células Gigantes/tratamento farmacológico , Arterite de Células Gigantes/epidemiologia , Humanos , Isquemia/complicações , AVC Isquêmico/epidemiologia , Arcada Osseodentária/irrigação sanguínea , Modelos Logísticos , Masculino , Metilprednisolona/uso terapêutico , Pessoa de Meia-Idade , Razão de Chances , Estudos Prospectivos , Fatores de Risco , Fumar/efeitos adversos , Transtornos da Visão/epidemiologia
15.
Clin Exp Rheumatol ; 38 Suppl 124(2): 23-30, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31573481

RESUMO

OBJECTIVES: To investigate serum levels of a panel of angiogenic inducers (VEGF, FGF-2, Angiopoietin 1, -2, soluble VCAM-1) and inhibitors (angiostatin, endostatin, pentraxin-3) in patients with giant cell arteritis (GCA) and Takayasu's arteritis (TAK), in order to gain further insights into the molecular mechanisms driving angiogenesis dysregulation in large-vessel vasculitis (LVV). METHODS: Sera were obtained from 33 TAK patients and 14 GCA patients and from two groups of age-matched normal controls (NC). Disease activity was assessed using 18F-FDG PET/CT and clinical indices including NIH/Kerr criteria and ITAS. Angiogenic and anti-angiogenic factor serum levels were evaluated using commercial ELISA kits. Pentraxin 3 (PTX3) serum levels were evaluated by non-commercial ELISA, as already described. RESULTS: Among the angiogenic factors, only VEGF serum levels were significantly higher in TAK patients compared to NC. No difference was found between angiogenic factor levels in GCA patients compared to those detected in NC. Anti-angiogenic factor (Angiostatin, Endostatin, PTX3) serum levels were significantly higher in both GCA and TAK patients compared to NC. Significant associations were observed between VEGF and PTX3 levels and disease activity evaluated using PET scan and clinical indices. Cluster analysis based on PET scan scores in TAK patients showed significant ordered differences in VEGF and angiostatin serum levels. Indeed, we noted a progressive increase of VEGF and angiostatin from NC to the cluster including patients with the highest and more diffuse scan positivity. CONCLUSIONS: Our overall results demonstrate a circulating molecular profile characterised by a prevailing expression of anti-angiogenic soluble factors.


Assuntos
Proteínas Angiogênicas/sangue , Proteínas Angiostáticas/sangue , Arterite de Células Gigantes/sangue , Arterite de Takayasu/sangue , Angiopoietina-1 , Angiopoietina-2 , Angiostatinas , Proteína C-Reativa , Endostatinas , Fator 2 de Crescimento de Fibroblastos , Humanos , Neovascularização Patológica/sangue , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Tomografia por Emissão de Pósitrons , Componente Amiloide P Sérico , Molécula 1 de Adesão de Célula Vascular , Fator A de Crescimento do Endotélio Vascular
16.
J Rheumatol ; 47(1): 99-107, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-30877209

RESUMO

OBJECTIVE: Disease activity in large-vessel vasculitis (LVV) is traditionally assessed by clinical and serological variables rather than vascular imaging. This study determined the effect of treatment on 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) vascular activity in relation to clinical- and serologic-based assessments. METHODS: Patients with giant cell arteritis (GCA) or Takayasu arteritis (TA) were prospectively evaluated at 6-month intervals in an observational cohort. Treatment changes were made at least 3 months before the followup visit and categorized as increased, decreased, or unchanged. Imaging (FDG-PET qualitative analysis), clinical, and serologic (erythrocyte sedimentation rate, C-reactive protein) assessments were determined at each visit and compared over interval visits. RESULTS: Serial assessments were performed in 52 patients with LVV (GCA = 31; TA = 21) over 156 visits. Increased, decreased, or unchanged therapy was recorded for 36-, 23-, and 32-visit intervals, respectively. When treatment was increased, there was significant reduction in disease activity by imaging, clinical, and inflammatory markers (p ≤ 0.01 for each). When treatment was unchanged, all 3 assessments of disease activity remained similarly unchanged over 6-month intervals. When treatment was reduced, PET activity significantly worsened (p = 0.02) but clinical and serologic activity did not significantly change. Treatment of GCA with tocilizumab and of TA with tumor necrosis factor inhibitors resulted in significant improvement in imaging and clinical assessments of disease activity, but only rarely did the assessments both become normal. CONCLUSION: In addition to clinical and serologic assessments, vascular imaging has potential to monitor disease activity in LVV and should be tested as an outcome measure in randomized clinical trials.


Assuntos
Antirreumáticos/uso terapêutico , Produtos Biológicos/uso terapêutico , Arterite de Células Gigantes/diagnóstico por imagem , Arterite de Células Gigantes/tratamento farmacológico , Glucocorticoides/uso terapêutico , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Arterite de Takayasu/diagnóstico por imagem , Arterite de Takayasu/tratamento farmacológico , Inibidores do Fator de Necrose Tumoral/uso terapêutico , Adulto , Idoso , Sedimentação Sanguínea/efeitos dos fármacos , Proteína C-Reativa/análise , Quimioterapia Combinada , Feminino , Fluordesoxiglucose F18/administração & dosagem , Seguimentos , Arterite de Células Gigantes/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Compostos Radiofarmacêuticos/administração & dosagem , Arterite de Takayasu/sangue , Resultado do Tratamento , Adulto Jovem
17.
Rheumatology (Oxford) ; 59(1): 176-184, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31292652

RESUMO

OBJECTIVES: PMR frequently co-occurs with GCA. So far, a simple biomarker for detecting concomitant arterial inflammation in PMR patients is lacking. Furthermore, biomarkers predicting disease course in PMR are awaited. We here investigated the diagnostic and prognostic value of acute-phase markers (ESR, CRP, IL-6, serum amyloid A) and angiogenesis markers (VEGF, soluble Tie2, angiopoietin-1, angiopoietin-2) in isolated PMR and PMR/GCA overlap patients. METHODS: We prospectively included 39 treatment-naïve PMR patients, of whom 10 patients also showed evidence of large vessel GCA by PET-CT. Age-matched healthy controls (n = 32) and infection controls (n = 13) were included for comparison. Serum marker levels were measured by an ELISA or Luminex assay. Receiver operating characteristic and Kaplan-Meier analyses were used to asses diagnostic and prognostic accuracy, respectively. RESULTS: All acute-phase and angiogenesis markers, except angiopoietin-1, were higher in isolated PMR patients than in healthy controls. Angiopoietin-2, ESR and soluble Tie-2 were significantly higher in patients with PMR/GCA overlap than in isolated PMR patients. Angiopoeietin-2, but not soluble Tie2, outperformed ESR and CRP in discriminating patients with and without overlapping GCA (area under the curve: 0.90; sensitivity: 100%; specificity: 76%). Moreover, high angiopoietin-2 levels were associated with long-term glucocorticoid requirement. CONCLUSION: Assessment of angiopoietin-2 at baseline may assist diagnosis of concomitant vasculitis in PMR. Moreover, high levels of angiopoietin-2 were associated with an unfavourable disease course in isolated PMR patients. These findings imply that angiopoietin-2 is an interesting diagnostic and prognostic biomarker in PMR.


Assuntos
Angiopoietina-2/sangue , Arterite de Células Gigantes/etiologia , Polimialgia Reumática/sangue , Prednisolona/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Proteína C-Reativa/metabolismo , Ensaio de Imunoadsorção Enzimática , Feminino , Seguimentos , Arterite de Células Gigantes/sangue , Arterite de Células Gigantes/diagnóstico , Glucocorticoides/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Polimialgia Reumática/complicações , Polimialgia Reumática/diagnóstico , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Prognóstico , Estudos Prospectivos
19.
Reumatol Clin (Engl Ed) ; 16(1): 38-41, 2020.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-29550251

RESUMO

OBJECTIVE: Polymyalgia rheumatica (PR) can be associated with large vessel vasculitis (LVV). We evaluate the diagnostic role of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) and its impact on the treatment of LVV associated with PR. MATERIALS AND METHODS: Retrospective study of patients diagnosed with PR. Data was collected from health records. Blood analysis included acute-phase reactants (APR), C-reactive protein (CRP) and erythrocyte sedimentation rate. An 18F-FDG PET/CT scan was performed in those patients whose symptoms persisted, in those with elevated APR, those who required higher doses of steroids or those who had atypical features of PR (low-grade fever, weight loss, among others). RESULTS: Twenty-three were eligible; 48% (n = 11) of the patients were diagnosed with LVV associated with PR. The site was heterogeneous, but mostly involved the aorta. In 80% of the patients with LVV, a disease-modifying antirheumatic drug was added to their treatment. Elevated CRP values were associated with the likelihood of presenting LVV. CONCLUSIONS: LVV is not uncommon, clinical features and elevated CRP levels should raise suspicion of LVV associated with PR. 18F-FDG PET/CT is useful in identifying LVV associated with PR.


Assuntos
Fluordesoxiglucose F18 , Polimialgia Reumática/complicações , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Compostos Radiofarmacêuticos , Vasculite Reumatoide/diagnóstico por imagem , Proteínas de Fase Aguda/análise , Idoso , Aortite/diagnóstico por imagem , Sedimentação Sanguínea , Proteína C-Reativa/análise , Feminino , Arterite de Células Gigantes/sangue , Arterite de Células Gigantes/complicações , Humanos , Masculino , Polimialgia Reumática/sangue , Polimialgia Reumática/tratamento farmacológico , Estudos Retrospectivos , Vasculite Reumatoide/sangue , Vasculite Reumatoide/tratamento farmacológico , Vasculite Reumatoide/etiologia
20.
Sci Rep ; 9(1): 14364, 2019 10 07.
Artigo em Inglês | MEDLINE | ID: mdl-31591421

RESUMO

Giant cell arteritis (GCA) is a medium- and large-vessel vasculitis with an onset age after 50 years. Takayasu arteritis (TA), which is also a large-vessel vasculitis with an onset age earlier than 40 years, was suggested to be associated with tuberculosis (TB). However, the association between GCA and TB was rarely reported. This study was to retrospectively analyze clinical data of GCA patients at Peking Union Medical College Hospital and elucidate the association between GCA and TB. Ninety-one patients diagnosed with GCA were included in the study. A total of 20 patients (22.0%) had a history of active tuberculosis and received anti-tuberculosis therapy. On comparing the clinical features of patients with GCA and concomitant TB and those without TB, obvious weight loss (P = 0.011), lower percentage of dyslipidemia (P = 0.042), higher percentage of anti-phospholipid antibodies (P = 0.010), and lower white blood cells (P = 0.006) were noted in the TB group. In conclusion, this study demonstrated the percentage of TB history in patients with GCA was higher than that in the Chinese general population. Clinicians should recognize the possibility of comorbid TB in patients with obvious weight loss and relatively lower white blood cell count.


Assuntos
Arterite de Células Gigantes/epidemiologia , Arterite de Takayasu/epidemiologia , Tuberculose/epidemiologia , Idade de Início , Idoso , Anticorpos Antifosfolipídeos/sangue , China/epidemiologia , Feminino , Arterite de Células Gigantes/sangue , Arterite de Células Gigantes/complicações , Arterite de Células Gigantes/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Arterite de Takayasu/sangue , Arterite de Takayasu/complicações , Arterite de Takayasu/patologia , Tuberculose/sangue , Tuberculose/complicações , Tuberculose/patologia
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