During a dengue outbreak on the Caribbean island Aruba, highly elevated levels of ferritin were d... more During a dengue outbreak on the Caribbean island Aruba, highly elevated levels of ferritin were detected in dengue virus infected patients. Ferritin is an acute-phase reactant and hyperferritinaemia is a hallmark of diseases caused by extensive immune activation, such as haemophagocytic lymphohistiocytosis. The aim of this study was to investigate whether hyperferritinaemia in dengue patients was associated with clinical markers of extensive immune activation and coagulation disturbances. Levels of ferritin, standard laboratory markers, sIL-2R, IL-18 and coagulation and fibrinolytic markers were determined in samples from patients with uncomplicated dengue in Aruba. Levels of ferritin were significantly increased in dengue patients compared to patients with other febrile illnesses. Moreover, levels of ferritin associated significantly with the occurrence of viraemia. Hyperferritinaemia was also significantly associated with thrombocytopenia, elevated liver enzymes and coagulation di...
Helper T cell differentiation (Th) is a key event in the development of the adaptive immune respo... more Helper T cell differentiation (Th) is a key event in the development of the adaptive immune response. By the production of a range of cytokines, Th cells determine the type of immune response that is raised against an invading pathogen. Th cells can adopt many different phenotypes and Th phenotype decision-making is crucial in mounting effective host responses. This review discusses the different Th phenotypes that have been identified and how Th cells adopt a particular phenotype. The regulation of Th phenotypes has been studied extensively using mathematical models, which have explored the role of regulatory mechanisms like autocrine cytokine signalling and cross-inhibition between self-activating transcription factors. At the single cell level, Th responses tend to be heterogeneous, but corrections can be made soon after T cell activation. Although pathogens and the innate immune system provide signals that direct the induction of Th phenotypes, these instructive mechanisms could be easily subverted by pathogens. We discuss a model of success-driven feedback would select the most appropriate phenotype for clearing a pathogen. Given the heterogeneity in the induction phase of the Th response, such a success-driven feedback loop would allow the selection of effective Th phenotypes while terminating incorrect responses. This article is protected by copyright. All rights reserved.
To investigate which cytokines and chemokines are involved in the immunopathogenesis of acute ret... more To investigate which cytokines and chemokines are involved in the immunopathogenesis of acute retinal necrosis (ARN), and whether cytokine profiles are associated with clinical manifestations, such as visual outcome. Serum and aqueous humor (AH) samples of 19 patients with ARN were analyzed by multiplex immunoassay. Infectious controls consisted of 18 patients with rubella virus-associated Fuchs' uveitis and 20 patients with ocular toxoplasmosis all confirmed by intraocular fluid analyses. The control group consisted of seven paired AH and serum samples from seven noninflammatory control patients with age-related cataract. In each sample, 4 anti-inflammatory, 12 proinflammatory, 2 vascular, and 4 other immune mediators were measured. In addition, various clinical characteristics were assessed. In ARN, 10 of the 22 mediators, including most proinflammatory and vascular mediators such as IL-6, IL-8, IL-18, MIF, MCP-1, Eotaxin, IP-10, IL-15, sICAM-1, and sVCAM-1, were significantly elevated when compared to all controls. In addition, one anti-inflammatory mediator (IL-10) was significantly elevated in ARN as compared to the controls. No association was found between the time of sampling and the extent and levels of immune mediator expression. The pathogenesis of ARN is characterized by the presence of predominantly proinflammatory cytokines and chemokines with high expression levels as compared to other infectious causes of uveitis. There are no indications for an obvious Th-1 or Th-17 pathway. The combined data suggest that immune mediator expression is related to severity of disease, which is more fulminant in ARN, rather than to a specific uveitis entity.
During a dengue outbreak on the Caribbean island Aruba, highly elevated levels of ferritin were d... more During a dengue outbreak on the Caribbean island Aruba, highly elevated levels of ferritin were detected in dengue virus infected patients. Ferritin is an acute-phase reactant and hyperferritinaemia is a hallmark of diseases caused by extensive immune activation, such as haemophagocytic lymphohistiocytosis. The aim of this study was to investigate whether hyperferritinaemia in dengue patients was associated with clinical markers of extensive immune activation and coagulation disturbances. Levels of ferritin, standard laboratory markers, sIL-2R, IL-18 and coagulation and fibrinolytic markers were determined in samples from patients with uncomplicated dengue in Aruba. Levels of ferritin were significantly increased in dengue patients compared to patients with other febrile illnesses. Moreover, levels of ferritin associated significantly with the occurrence of viraemia. Hyperferritinaemia was also significantly associated with thrombocytopenia, elevated liver enzymes and coagulation di...
Helper T cell differentiation (Th) is a key event in the development of the adaptive immune respo... more Helper T cell differentiation (Th) is a key event in the development of the adaptive immune response. By the production of a range of cytokines, Th cells determine the type of immune response that is raised against an invading pathogen. Th cells can adopt many different phenotypes and Th phenotype decision-making is crucial in mounting effective host responses. This review discusses the different Th phenotypes that have been identified and how Th cells adopt a particular phenotype. The regulation of Th phenotypes has been studied extensively using mathematical models, which have explored the role of regulatory mechanisms like autocrine cytokine signalling and cross-inhibition between self-activating transcription factors. At the single cell level, Th responses tend to be heterogeneous, but corrections can be made soon after T cell activation. Although pathogens and the innate immune system provide signals that direct the induction of Th phenotypes, these instructive mechanisms could be easily subverted by pathogens. We discuss a model of success-driven feedback would select the most appropriate phenotype for clearing a pathogen. Given the heterogeneity in the induction phase of the Th response, such a success-driven feedback loop would allow the selection of effective Th phenotypes while terminating incorrect responses. This article is protected by copyright. All rights reserved.
To investigate which cytokines and chemokines are involved in the immunopathogenesis of acute ret... more To investigate which cytokines and chemokines are involved in the immunopathogenesis of acute retinal necrosis (ARN), and whether cytokine profiles are associated with clinical manifestations, such as visual outcome. Serum and aqueous humor (AH) samples of 19 patients with ARN were analyzed by multiplex immunoassay. Infectious controls consisted of 18 patients with rubella virus-associated Fuchs' uveitis and 20 patients with ocular toxoplasmosis all confirmed by intraocular fluid analyses. The control group consisted of seven paired AH and serum samples from seven noninflammatory control patients with age-related cataract. In each sample, 4 anti-inflammatory, 12 proinflammatory, 2 vascular, and 4 other immune mediators were measured. In addition, various clinical characteristics were assessed. In ARN, 10 of the 22 mediators, including most proinflammatory and vascular mediators such as IL-6, IL-8, IL-18, MIF, MCP-1, Eotaxin, IP-10, IL-15, sICAM-1, and sVCAM-1, were significantly elevated when compared to all controls. In addition, one anti-inflammatory mediator (IL-10) was significantly elevated in ARN as compared to the controls. No association was found between the time of sampling and the extent and levels of immune mediator expression. The pathogenesis of ARN is characterized by the presence of predominantly proinflammatory cytokines and chemokines with high expression levels as compared to other infectious causes of uveitis. There are no indications for an obvious Th-1 or Th-17 pathway. The combined data suggest that immune mediator expression is related to severity of disease, which is more fulminant in ARN, rather than to a specific uveitis entity.
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