Anaphylaxis: Mediators, Biomarkers, and Microenvironments.

The life-threatening nature of anaphylactic reactions has increased interest in discovering new biomarkers that could improve diagnosis and prevention. However, the diverse nature of the clinical features and the etiology and pathogenesis of anaphylaxis hinder the identification of valuable molecular indicators of disease. Most studies on anaphylaxis focus on the immune system. Anaphylactic reactions are characterized primarily by IgE-mediated activation of mast cells and basophils and release of mediators. Determination of serum tryptase levels is the main in vitro test used to confirm the reaction, although there are no biomarkers that can predict it. Nevertheless, recent research has postulated that alternative pathways, cell types, and systems are involved. Consequently, various molecular products have been explored and considered potential biomarkers, although none of them are yet used in clinical practice. The products that are altered in patients with anaphylaxis include vasoactive agents, proteases, proteoglycans, lipids, interleukins, cytokines, products of the complement-contact and coagulation systems, circulating proteins, extracellular vesicles, microRNAs, and metabolites. The recognition of biological processes and molecular pathways affecting the microenvironments involved in anaphylaxis will considerably improve clinical practice and the identification of better molecular markers. We offer a broad review of the various mediators described in anaphylaxis, consider their usefulness as potential biomarkers of this pathological event, and examine their role in the molecular basis of the reaction.

Allergen Profile of London Plane Tree Pollen: Clinical and Molecular Pattern in Central Spain.

BACKGROUND AND OBJECTIVES: Platanus acerifolia (London plane tree) is a deciduous tree of the Platanaceae family. Sensitization to this plant varies with geography. Madrid, located in central Spain, has one of the highest London plane tree pollen concentration levels on the Iberian Peninsula. We evaluated both the clinical characteristics and the molecular sensitization pattern of patients with allergy to London plane tree pollen in the region of Madrid. METHODS: Thirty-eight patients allergic to London plane tree pollen were selected according to their clinical symptoms and positive results in skin prick testing and/or specific IgE determination. Serum was collected, and allergen components were evaluated using immunodetection techniques as well as ImmunoCAP. The IgE-binding proteins detected were identified and characterized using mass spectrometry. RESULTS: Analysis of serum samples from allergic patients revealed 9 IgE-binding bands in London plane tree pollen extract. Among these, the 45-kDa protein, which corresponded to Pla a 2, was detected in 76.3% of patients. However, the 18-kDa (Pla a 1) and 9-kDa (Pla a 3) bands were detected in 44.7% and 23.7% of sera, respectively. These results were confirmed using purified proteins. Characterization of the allergen revealed the 27-kDa protein to be glutathione-S-transferase. CONCLUSIONS: The molecular profile of patients sensitized to London plane tree pollen differs from that reported in studies from other locations. In the population we studied, the prevalence of Pla a 2 was higher than that of Pla a 1 and Pla a 3. In addition, the minor allergen previously referred to as Pla a 4 was characterized as glutathione-S-transferase.

Allergen Profile of London Plane Tree Pollen: Clinical and Molecular Pattern in Central Spain

Background: Platanus acerifolia (London plane tree) is a deciduous tree of the Platanaceae family. Sensitization to this plant varies withgeography. Madrid, located in central Spain, has one of the highest London plane tree pollen concentration levels on the Iberian Peninsula.Objectives: We evaluated both the clinical characteristics and the molecular sensitization pattern of patients with allergy to London planetree pollen in the region of Madrid.Patients and Methods: Thirty-eight patients allergic to London plane tree pollen were selected according to their clinical symptoms andpositive results in skin prick testing and/or specific IgE determination. Serum was collected, and allergen components were evaluatedusing immunodetection techniques as well as ImmunoCAP. The IgE-binding proteins detected were identified and characterized usingmass spectrometry.Results: Analysis of serum samples from allergic patients revealed 9 IgE-binding bands in London plane tree pollen extract. Among these,the 45-kDa protein, which corresponded to Pla a 2, was detected in 76.3% of patients. However, the 18-kDa (Pla a 1) and 9-kDa (Pla a 3)bands were detected in 44.7% and 23.7% of sera, respectively. These results were confirmed using purified proteins. Characterization ofthe allergen revealed the 27-kDa protein to be glutathione-S-transferase.Conclusions: The molecular profile of patients sensitized to London plane tree pollen differs from that reported in studies from otherlocations. In the population we studied, the prevalence of Pla a 2 was higher than that of Pla a 1 and Pla a 3. In addition, the minorallergen previously referred to as Pla a 4 was characterized as glutathione-S-transferase. (AU)

Antecedentes: Platanus acerifolia es un árbol de hoja caduca de la familia Platanaceae. La sensibilización frente a esta planta varía enfunción de la zona geográfica. Madrid, ubicada en el centro de España, tiene uno de los mayores niveles de concentración de polen deeste árbol en la Península Ibérica.Objetivo: Evaluar las características clínicas y los patrones moleculares de sensibilización en pacientes con alergia al plátano de sombraen la región de Madrid.Pacientes y Métodos: Treinta y ocho pacientes alérgicos al polen del plátano de sombra fueron seleccionados de acuerdo con los síntomasclínicos, pruebas cutáneas positivas y/o IgE específica. El suero se recogió y se evaluaron los componentes alérgicos mediante técnicas deinmunodetección, así como ImmunoCAP. Las proteínas que unían IgE fueron identificadas y caracterizadas por espectrometría de masas.Resultados: El análisis de los sueros de los pacientes alérgicos reveló 9 bandas que captaban IgE en los extractos de polen de plátano desombra. Entre estas, la proteína de 45 kDa, correspondiente a Pla a 2, se detectó en el 76,3% de los pacientes. Sin embargo, las bandasde 18 kDa (Pla a 1) y 9 kDa (Pla a 3) fueron reconocidas en el 44,7% y 27,3%, respectivamente. Estos resultados se confirmaron usandoproteínas purificadas. La caracterización de los alérgenos identificó la proteína de 27 kDa como una glutatión S-transferasa.Conclusiones: El perfil molecular de los pacientes sensibilizados al polen del plátano de sombra varía respecto al descrito en estudios deotras localizaciones. Nuestra población muestra una mayor prevalencia de Pla a 2 comparado con Pla a 1 y Pla a 3. Además, el alérgenominoritario previamente denominado Pla a 4 fue caracterizado como una glutatión-S-transferasa. (AU)

Anaphylaxis: Mediators, Biomarkers, and Microenvironments

The life-threatening nature of anaphylactic reactions has increased interest in discovering new biomarkers that could improve diagnosis and prevention. However, the diverse nature of the clinical features and the etiology and pathogenesis of anaphylaxis hinder the identification of valuable molecular indicators of disease. Most studies on anaphylaxis focus on the immune system. Anaphylactic reactions are characterized primarily by IgE-mediated activation of mast cells and basophils and release of mediators. Determination of serum tryptase levels is the main in vitro test used to confirm the reaction, although there are no biomarkers that can predict it. Nevertheless, recent research has postulated that alternative pathways, cell types, and systems are involved. Consequently, various molecular products have been explored and considered potential biomarkers, although none of them are yet used in clinical practice. The products that are altered in patients with anaphylaxis include vasoactive agents, proteases, proteoglycans, lipids, interleukins, cytokines, products of the complement-contact and coagulation systems, circulating proteins, extracellular vesicles, microRNAs, and metabolites. The recognition of biological processes and molecular pathways affecting the microenvironments involved in anaphylaxis will considerably improve clinical practice and the identification of better molecular markers. We offer a broad review of the various mediators described in anaphylaxis, consider their usefulness as potential biomarkers of this pathological event, and examine their role in the molecular basis of the reaction (AU)

Porin: a new button mushroom (Agaricus bisporus) allergen

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[Photodynamic therapy in retinal pigment epithelium detachment associated with long term central serous chorioretinopathy]. / Terapia fotodinámica en DEP avascular asociado a coriorretinopatía serosa central de larga evolución.

PURPOSE: To present a case of long term central serous corioretinopathy associated with chronic detachment of the retinal pigment epithelium (RPE) and the effect of photodynamic therapy on it. CASE CLINIC: We present the case of a 46-year old man with long term chronic central serous chorioretinopathy (18 mo.) with chronic detachment of RPE in his left eye who underwent PDT with Verteporfin (Visudyne). BCVA improved from 0.7 to 1 and metamorphopsia disappeared within one month of treatment. The patient remained asymptomatic for a follow-up period of 15 months. DISCUSSION: Choroidal hyperpermeability is found in central serous chorioretinopathy as a primary involvement factor. PDT with Verteporfin induces a transient reduction in choriocapilaris blood flow and can be used as treatment in cases of chronic central serous chorioretinopathy.

Terapia fotodinámica en Dep avascular asociado a coriorretinopatía serosa central de larga evolución / Photodynamic therapy in retinal pigment epitheliyn detachment associated with long term central serous chorioretinopathy

Objetivo: Describir un caso de coriorretinopatía serosa central asociada a un DEP crónico y el resultado de terapia fotodinámica sobre el mismo. Caso clínico: Se presenta el caso de un hombre de 46 años con coriorretinopatía serosa central crónica de larga evolución (18 meses) con desprendimiento crónico del EPR en su ojo izquierdo que se sometió a tratamiento con terapia fotodinámica con Verteporfin (Visudyne). La AV mejoró de 0,7 a 1, desapareciendo la metamorfopsia en un mes tras el tratamiento. El paciente permaneció asintomático durante un periodo de seguimiento de 15 meses. Discusión: La hiperpermeabilidad coroidea es un factor primario en el desarrollo de la coriorretinopatía serosa central. La terapia fotodinámica con Verteporfin induce una reducción transitoria en el flujo sanguíneo de la coriocapilar y se puede usar como tratamiento en casos de coriorretinopatía serosa central crónica

Purpose: To present a case of long term central serous corioretinopathy associated with chronic detachment of the retinal pigment epithelium (RPE) and the effect of photodynamic therapy on it. Case clinic: We present the case of a 46-year old man with long term chronic central serous chorioretinopathy (18 mo.) with chronic detachment of RPE in his left eye who underwent PDT with Verteporfin (Visudyne). BCVA improved from 0.7 to 1 and metamorphopsia disappeared within one month of treatment. The patient remained asymptomatic for a follow-up period of 15 months. Discussion: Choroidal hyperpermeability is found in central serous chorioretinopathy as a primary involvement factor. PDT with Verteporfin induces a transient reduction in choriocapilaris blood flow and can be used as treatment in cases of chronic central serous chorioretinopathy (Arch Soc Esp Oftalmol 2008; 83: 545-548)

[Evaluation of four new discriminant functions for HRT II in glaucoma diagnosis]. / Evaluación de cuatro nuevas funciones discriminantes del HRT II para el diagnóstico del glaucoma.

PURPOSE: To assess the diagnostic usefulness of four linear discriminant functions for Heidelberg retina tomograph (HRT) II obtained in our population. METHODS: 450 eyes of 450 patients were studied. Eyes were classified as those of healthy subjects (101), those with ocular hypertension (126), those suspected to have glaucoma (121) or those with glaucoma (103). Intraocular pressure, optic nerve head appearance in stereophotographs, and standard automated perimetry results were assessed. ANOVAs among the groups were calculated for all global parameters and the 4 formulas. Receiver operating characteristic (ROC) curves were plotted for the 4 multivariate functions designed in our hospital and the areas under the ROC curves were compared. Sensitivity at 80% and 90% fixed specificities were also calculated. RESULTS: All functions discriminated well between healthy and glaucoma suspects, and between healthy and glaucomatous eyes. At 90% fixed specificity, sensitivities ranged from 54% to 60% in differentiating between healthy and glaucoma suspects, and from 65% to 68% in discriminating between control and glaucoma subjects. No differences were found between the areas under the ROC curves of these functions. CONCLUSIONS: The evaluated linear discriminant functions increased the diagnostic ability of HRT II isolated parameters in detecting glaucoma. These functions performed better than the HRT-provided discriminant functions.

[Diagnostic ability of GDx VCC for glaucoma diagnosis]. / Capacidad diagnóstica del GDx VCC para el diagnóstico del glaucoma.

PURPOSE: To assess the diagnostic ability of scanning laser polarimetry (GDx VCC) to differentiate between normal and glaucomatous eyes. METHODS: 417 eyes of 417 consecutive subjects were prospectively selected. They were classified into 60 healthy controls, 218 ocular hypertensive eyes, 68 glaucoma suspects, and 71 glaucomatous eyes, depending on intraocular pressure, optic nerve head morphology and standard automated perimetry results. All underwent a scanning laser polarimetry with the GDx VCC. Retinal nerve fiber layer (RNFL) parameters of the GDx-VCC were compared among the four groups. Receiver operating characteristic (ROC) curves were plotted between normal and glaucomatous eyes. The best parameters were defined according to the area under the ROC curve and the best sensitivity/specificity balance. RESULTS: Most parameters of GDx-VCC exhibited differences between the glaucoma group and the rest of the groups. Some parameters were also different between healthy patients and glaucoma suspects. The best parameter was the nerve fiber indicator (NFI; area under the ROC curve: 0.876). NFI, superior normalized area, and inferior normalized area yielded the highest sensitivities at 85% and 90% fixed specificity. CONCLUSIONS: Most RNFL parameters measured with the GDx-VCC provided good diagnostic ability for open-angle glaucoma. The best GDx-VCC parameter in differentiating between normal and glaucomatous eyes was the NFI.

Evaluación de cuatro nuevas funciones discriminantes del HRT II para el diagnóstico del glaucoma / Evaluation of four new discriminant functions for HRT II glaucoma diagnosis

Objetivo: Valorar la capacidad diagnóstica de cuatro fórmulas discriminantes diseñadas para el Heidelberg retina Tomograph (HRT) II a partir de nuestra población. Material y método: Se incluyeron 450 ojos de 450 pacientes. Fueron clasificados según la presión intraocular, morfología papilar en estereofotografías y los resultados de la perimetría automatizada convencional en 101 ojos normales, 126 hipertensos oculares, 121 sospechosos de glaucoma y 102 ojos con glaucoma. Se calcularon las ANOVAs entre los grupos para todos los parámetros globales y las cuatro fórmulas. Se trazaron las curvas ROC para las cuatro funciones discriminantes diseñadas en nuestro hospital y se compararon las áreas bajo las curvas. Se calcularon los valores de sensibilidad para especificidades fijadas en el 80% y 90%. Resultados: Las cuatro fórmulas discriminaron bien entre el grupo control y los sospechosos de glaucoma, y entre controles y glaucomas. Para una especificidad fijada en el 90%, las sensibilidades oscilaron entre el 54% y 60% para diferenciar entre sanos y sospechosos de glaucoma, y entre el 65% y 68% para diferenciar entre sanos y glaucomas. No se observaron diferencias en las áreas bajo la curva de las distintas fórmulas. Conclusiones: Las fórmulas discriminantes evaluadas aumentaron la capacidad diagnóstica de los parámetros aislados del HRT II para detectar glaucomas. Asimismo, mostraron mejor rendimiento que las fórmulas discriminantes incluidas en el HRT

Purpose: To assess the diagnostic usefulness of four linear discriminant functions for Heidelberg retina tomograph (HRT) II obtained in our population. Methods: 450 eyes of 450 patients were studied. Eyes were classified as those of healthy subjects (101), those with ocular hypertension (126), those suspected to have glaucoma (121) or those with glaucoma (103). Intraocular pressure, optic nerve head appearance in stereophotographs, and standard automated perimetry results were assessed. ANOVAs among the groups were calculated for all global parameters and the 4 formulas. Receiver operating characteristic (ROC) curves were plotted for the 4 multivariate functions designed in our hospital and the areas under the ROC curves were compared. Sensitivity at 80% and 90% fixed specificities were also calculated. Results: All functions discriminated well between healthy and glaucoma suspects, and between healthy and glaucomatous eyes. At 90% fixed specificity, sensitivities ranged from 54% to 60% in differentiating between healthy and glaucoma suspects, and from 65% to 68% in discriminating between control and glaucoma subjects. No differences were found between the areas under the ROC curves of these functions. Conclusions: The evaluated linear discriminant functions increased the diagnostic ability of HRT II isolated parameters in detecting glaucoma. These functions performed better than the HRT-provided discriminant functions (Arch Soc Esp Oftalmol 2008; 83: 349-356)