(18)F-Fluorodeoxyglucose positron emission tomography and serum cytokines and matrix metalloproteinases in the assessment of disease activity in Takayasu's arteritis.

OBJECTIVE: To evaluate (18)F-fluorodeoxyglucose ((18)F-FDG) uptake on positron emission tomography-computed tomography (PET-CT) and serum levels of different cytokines and matrix metalloproteinases (MMPs) in patients with Takayasu arteritis (TA) and associations with disease activity. METHODS: Serum levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-2, IL-6, IL-8, IL-12, IL-18, MMP-3 and MMP-9 were measured in 36 TA patients and 36 controls. Maximum standard uptake value (SUVmax) of (18)F-FDG in arterial walls was determined by PET-CT scans. TA patients were classified as active disease, inactive disease and possible active disease. RESULTS: Serum IL-6 and MMP-3 levels were higher in TA patients than in controls (p<0.001). Serum IL-6 was higher in patients with active disease and in patients with possible active disease than in inactive disease (p<0.0001). Patients with active disease had higher serum TNFα levels than patients with inactive disease (p=0.049) while patients with possible active disease presented higher IL-18 levels than patients with inactive disease (p=0.046). Patients with active disease had higher SUVmax values than those with inactive disease (p=0.042). By receiver operating characteristic (ROC) curve SUVmax was predictive of active disease in TA and values ≥1.3 were associated with disease activity (p=0.039). Serum TNF-α levels were higher in patients with SUVmax≥1.3 than <1.3 (p=0.045) and controls (p=0.012). Serum IL-6 levels were higher in patients with SUVmax≥1.3 than in controls (p<0.001). No differences regarding other biomarkers were found between TA patients and controls. CONCLUSIONS: Higher serum IL-6 and TNFα levels as well as higher (18)F-FDG uptake in arterial wall are associated with active TA.

18F-Fluorodeoxyglucose positron emission tomography and serum cytokines and matrix metalloproteinases in the assessment of disease activity in Takayasu's arteritis / Tomografia por emissão de pósitrons com 18F-fluordesoxiglicose e citocinas séricas e metaloproteinases da matriz na avaliação da atividade da doença na arterite de Takayasu

ABSTRACT Objective: To evaluate 18F-fluorodeoxyglucose (18F-FDG) uptake on positron emission tomography–computed tomography (PET–CT) and serum levels of different cytokines and matrix metalloproteinases (MMPs) in patients with Takayasu arteritis (TA) and associations with disease activity. Methods: Serum levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-2, IL-6, IL-8, IL-12, IL-18, MMP-3 and MMP-9 were measured in 36 TA patients and 36 controls. Maximum standard uptake value (SUVmax) of 18F-FDG in arterial walls was determined by PET–CT scans. TA patients were classified as active disease, inactive disease and possible active disease. Results: Serum IL-6 and MMP-3 levels were higher in TA patients than in controls (p < 0.001). Serum IL-6 was higher in patients with active disease and in patients with possible active disease than in inactive disease (p < 0.0001). Patients with active disease had higher serum TNFα levels than patients with inactive disease (p = 0.049) while patients with possible active disease presented higher IL-18 levels than patients with inactive disease (p = 0.046). Patients with active disease had higher SUVmax values than those with inactive disease (p = 0.042). By receiver operating characteristic (ROC) curve SUVmax was predictive of active disease in TA and values ≥1.3 were associated with disease activity (p = 0.039). Serum TNF-α levels were higher in patients with SUVmax ≥ 1.3 than <1.3 (p = 0.045) and controls (p = 0.012). Serum IL-6 levels were higher in patients with SUVmax ≥ 1.3 than in controls (p < 0.001). No differences regarding other biomarkers were found between TA patients and controls. Conclusions: Higher serum IL-6 and TNFα levels as well as higher 18F-FDG uptake in arterial wall are associated with active TA.

RESUMO Objetivo: Avaliar a captação de 18F-fluordesoxiglicose (FDG) na tomografia por emissão de pósitrons – tomografia computadorizada (PET-CT) – e os níveis séricos de diferentes citocinas e da metaloproteinases da matriz (MMP) em pacientes com arterite de Takayasu (AT) e associações com a atividade da doença. Métodos: Foram mensurados os níveis séricos do fator de necrose tumoral-α (TNF-α), interleucina (IL)-2, IL-6, IL-8, IL-12, IL-18, MMP-3 e MMP-9 em 36 pacientes com AT e 36 controles. O valor padronizado de captação máximo (SUVmax) de 18F-FDG nas paredes arteriais foi determinado por exames de PET-CT. Os pacientes com AT foram classificados como doença ativa, doença inativa e possível doença ativa. Resultados: Os níveis séricos de IL-6 e MMP-3 foram mais altos em pacientes com AT do que nos controles (p < 0,001). Os níveis séricos de IL-6 foram mais elevados em pacientes com doença ativa e em pacientes com possível doença ativa do que naqueles com doença inativa (p < 0,0001). Os pacientes com doença ativa apresentaram níveis séricos mais elevados de TNF-α do que os pacientes com doença inativa (p = 0,049), enquanto os indivíduos com possível doença ativa apresentaram maiores níveis séricos de IL-18 do que os pacientes com doença inativa (p = 0,046). Aqueles com doença ativa apresentaram maiores valores de SUVmax do que aqueles com doença inativa (p = 0,042). De acordo com a curva ROC, o SUVmax foi capaz de predizer a doença ativa na AT e valores ≥ 1,3 estavam associados à atividade da doença (p = 0,039). Os níveis séricos de TNF-α foram maiores em pacientes com SUVmax ≥ 1,3 do que naqueles com valor < 1,3 (p = 0,045) e controles (p = 0,012). Os níveis séricos de IL-6 foram mais elevados em pacientes com SUVmax ≥ 1,3 do que nos controles (p < 0,001). Não foram encontradas diferenças em relação a outros biomarcadores entre pacientes com AT e controles. Conclusões: Níveis séricos elevados de IL-6 e TNF-α, bem como uma maior captação arterial de 18F-FDG, estão associados à AT ativa.

[18F-Fluorodeoxyglucose positron emission tomography and serum cytokines and matrix metalloproteinases in the assessment of disease activity in Takayasu's arteritis]. / Tomografia por emissão de pósitrons com 18F-fluordesoxiglicose e citocinas séricas e metaloproteinases da matriz na avaliação da atividade da doença na arterite de Takayasu.

OBJECTIVE: To evaluate 18F-fluorodeoxyglucose (FDG) uptake on positron emission tomography-computed tomography (PET-CT)-and serum levels of different cytokines and matrix metalloproteinases (MMPs) in patients with Takayasu's arteritis (TA) and associations with disease activity. METHODS: Serum levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-2, IL-6, IL-8, IL-12, IL-18, MMP-3 and MMP-9 were measured in 36 TA patients and 36 controls. Maximum standard uptake value (SUVmax) of 18F-FDG in arterial walls was determined by PET-CT scans. TA patients were classified as active disease, inactive disease and possible active disease. RESULTS: Serum IL-6 and MMP-3 levels were higher in TA patients than in controls (p<0.001). Serum IL-6 was higher in patients with active disease and in patients with possible active disease than in inactive disease (p<0.0001). Patients with active disease had higher serum TNFα levels than patients with inactive disease (p=0.049) while patients with possible active disease presented higher IL-18 levels than patients with inactive disease (p=0.046). Patients with active disease had higher SUVmax values than those with inactive disease (p=0.042). By ROC curve SUVmax was predictive of active disease in TA and values ≥1.3 were associated with disease activity (p=0.039). Serum TNF-α levels were higher in patients with SUVmax ≥1.3 than<1.3 (p=0.045) and controls (p=0.012). Serum IL-6 levels were higher in patients with SUVmax ≥1.3 than in controls (p<0.001). No differences regarding other biomarkers were found between TA patients and controls. CONCLUSIONS: Higher serum IL-6 and TNFα levels as well as higher arterial 18F-FDG uptake are associated with active TA.

Antiplatelet therapy for the prevention of arterial ischemic events in takayasu arteritis.

BACKGROUND: Vessel wall inflammation, atherosclerosis and hypercoagulability may be responsible for ischemic events in Takayasu arteritis (TA). No study has evaluated the effect of antiplatelet therapy for the prevention of ischemic events in TA. METHODS AND RESULTS: Forty-eight patients who met the ACR Classification Criteria for TA under follow-up at the Vasculitis Unit of Universidade Federal de São Paulo were evaluated retrospectively for clinical manifestations, therapy and arterial ischemic events. The mean age at study was 38.0 years and the mean age at TA diagnosis was 29.1 years. Women comprised for 89.6% of patients and 60.4% were Caucasian. Risk factors for cardiovascular disease were found in 44 patients (91.7%) The most common comorbidities for TA patients were hypertension (77.1%), high low-density lipoprotein (45.8%) and obesity (16.7%). Antiplatelet therapy was used by 62.5% of patients whereas anticoagulants were used by 12.5%. Acute ischemic events occurred in 29.2% of patients. TA patients with ischemic events used significantly less antiplatelet agents (14.3%) than those without ischemic events (82.4%), P<0.0001. No difference concerning ischemic events was observed in patients on anticoagulant therapy (P=0.339). The 3 deaths of TA patients were observed only in those who had presented ischemic events (P=0.021). Antiplatelet agents had a protective effect against ischemic events (hazard ratio =0.055, 95% confidence interval: 0.06-0.514; P=0.011). CONCLUSIONS: Antiplatelet therapy is associated with a lower frequency of ischemic events in patients with TA.