RESUMEN
BACKGROUND: Endothelial cell dysfunction is believed to play an important role in the pathogenesis of plasma leakage in patients with acute dengue virus (DENV) infection. Several factors, produced by activated endothelial cells, have been associated with plasma leakage or severe disease in patients with infectious diseases. OBJECTIVES: The aim of this study was to investigate which of these markers could serve as a surrogate marker for the occurrence of plasma leakage in patients with acute DENV infection. STUDY DESIGN: A case-control study was performed in patients with acute DENV infection in Santos, Brazil. Plasma leakage was detected with X-ray and/or ultrasound examination at admission. Serum levels of soluble endoglin, endothelin-1, angiopoietin-2, VEGF, soluble VEGFR-2, MMP-2, MMP-9, TIMP-1 and TIMP-2 were determined using commercially available ELISAs. RESULTS: Increased levels of angiopoietin-2, endothelin-1 and MMP-2 and decreased levels of soluble VEGFR-2 were significantly associated with the occurrence of plasma leakage. An unsupervised cluster analysis confirmed that angiopoietin-2 and soluble VEGFR-2 were strongly associated with clinical apparent vascular leakage. CONCLUSION: Angiopoietin-2 and soluble VEGFR-2 can serve as surrogate markers for the occurrence of plasma leakage in patients with acute DENV infection.
Asunto(s)
Angiopoyetina 2/sangre , Permeabilidad Capilar/fisiología , Dengue Grave/sangre , Receptor 2 de Factores de Crecimiento Endotelial Vascular/sangre , Adolescente , Adulto , Anticuerpos Antivirales/inmunología , Afinidad de Anticuerpos/inmunología , Biomarcadores/sangre , Brasil , Estudios de Casos y Controles , Niño , Virus del Dengue/patogenicidad , Células Endoteliales/patología , Células Endoteliales/virología , Endotelina-1/sangre , Femenino , Humanos , Inmunoglobulina G/inmunología , Masculino , Metaloproteinasa 2 de la Matriz/sangre , Persona de Mediana Edad , Radiografía , Dengue Grave/diagnóstico por imagen , Dengue Grave/virología , Adulto JovenRESUMEN
BACKGROUND: Severe dengue virus (DENV) disease is associated with extensive immune activation, characterized by a cytokine storm. Previously, elevated lipopolysaccharide (LPS) levels in dengue were found to correlate with clinical disease severity. In the present cross-sectional study we identified markers of microbial translocation and immune activation, which are associated with severe manifestations of DENV infection. METHODS: Serum samples from DENV-infected patients were collected during the outbreak in 2010 in the State of São Paulo, Brazil. Levels of LPS, lipopolysaccharide binding protein (LBP), soluble CD14 (sCD14) and IgM and IgG endotoxin core antibodies were determined by ELISA. Thirty cytokines were quantified using a multiplex luminex system. Patients were classified according to the 2009 WHO classification and the occurrence of plasma leakage/shock and hemorrhage. Moreover, a (non-supervised) cluster analysis based on the expression of the quantified cytokines was applied to identify groups of patients with similar cytokine profiles. Markers of microbial translocation were linked to groups with similar clinical disease severity and clusters with similar cytokine profiles. RESULTS: Cluster analysis indicated that LPS levels were significantly increased in patients with a profound pro-inflammatory cytokine profile. LBP and sCD14 showed significantly increased levels in patients with severe disease in the clinical classification and in patients with severe inflammation in the cluster analysis. With both the clinical classification and the cluster analysis, levels of IL-6, IL-8, sIL-2R, MCP-1, RANTES, HGF, G-CSF and EGF were associated with severe disease. CONCLUSIONS: The present study provides evidence that both microbial translocation and extensive immune activation occur during severe DENV infection and may play an important role in the pathogenesis.
Asunto(s)
Traslocación Bacteriana/inmunología , Citocinas/sangre , Dengue Grave/complicaciones , Dengue Grave/patología , Adolescente , Adulto , Brasil/epidemiología , Niño , Brotes de Enfermedades , Femenino , Humanos , Masculino , Persona de Mediana Edad , Dengue Grave/inmunología , Adulto JovenRESUMEN
INTRODUCTION: This study prospectively accessed the immune response to the inactivated influenza vaccine in renal transplant recipients receiving either azathioprine or mycophenolate mofetil (MMF). Side effects were investigated. METHODS: Sixty-nine patients received one dose of inactivated trivalent influenza vaccine. Antihemagglutinin (HI) antibody response against each strain was measured before and one to six months after vaccination. RESULTS: Geometric mean HI antibody titers for H1N1 and H3N2 strains increased from 2.57 and 2.44 to 13.45 (p = 0.001) and 7.20 (p < 0.001), respectively. Pre- and post-vaccination protection rates for H1N1 and H3N2 increased from 8.7% to 49.3% (p < 0.001); and 36.3% (p < 0.001) and seroconversion rates were 36% and 25.3%, respectively. There was no response to influenza B. The use of MMF reduced the H1N1 and H3N2 protection rates and the seroconversion rate for the H1N1 strain when compared with the use of azathioprine, and subjects transplanted less than 87 months also had inferior antibody response. Adverse events were mild and there were no change on renal function post-vaccination. CONCLUSION: Renal transplant patients vaccinated against influenza responded with antibody production for influenza A virus strains, but not for influenza B. Use of MMF and shorter time from transplantation decreased the immune response to the vaccine.