Presentación    
DRUG HYPERSENSIBILITY AND
INNATE IMMUNE RESPONSE
Composition
Name
Position
Institution
Teresa Bellón Heredia
Investigadora Senior (Contrato Miguel Servet -I2)
Jefe de laboratorio
Hospital Universitario La Paz
María del Rosario Cabañas Moreno
Facultativo Especialista de Área en Alergología
Hospital Universitario La Paz
Francisco José de Abajo Iglesias
Facultativo Especialista de Área en Farmacología
Profesor Titular. Facultad de Medicina
Hospital Universitario Príncipe de Asturias.
Universidad de Alcalá
Jessica González Ramos
Médico Interno Residente en Dermatología
Hospital Universitario La Paz
Victoria Lerma Hambleton
Coordinadora de casos del estudio PIELenRed
Hospital Universitario Príncipe de Asturias
Aranzazú Isabel Rodríguez Sanz
Investigadora Postdoctoral
Hospital Universitario La Paz
Gaston Roustan Gullón
Facultativo Especialista de Área en Dermatología
Profesor Asociado. Facultad de Medicina
Hospital Universitario Puerta de Hierro
Universidad Autónoma de Madrid
 
Strategic Objective
Cutaneous adverse drug reactions are unpredictable and represent a plethora of skin diseases with various degrees of severity. The spectrum ranges from mild to potentially fatal multisystem maladies. Those of most concern are usually referred to as severe cutaneous adverse reactions (SCARs), and include acute generalized exanthematous pustulosis (AGEP), drug reaction with eosinophilia and systemic symptoms (DRESS), also known as drug induced hypersensitivity syndrome or hypersensitivity syndrome (DIHS/HSS), Stevens-Johnson’s syndrome (SJS), and toxic epidermal necrolysis (TEN). Among them, SJS and TEN are the most severe clinical entities and are nowadays considered as variants of the same disease characterized by keratinocyte necrosis and epidermal detachment with the formation of subepidermal bullae. From the immunopatohogenic point of view, SCARs are T-cell mediated type IV hypersensitivity reactions. However, T cells can orchestrate different types of immune responses and this functional heterogeneity has led to a further sub-classification into type IVa-IVd hypersensitivity that considers the distinct cytokine production pattern by T cell subpopulations, and emphasizes the participation of different effector cells causing inflammation and tissue damage. Current knowledge supports the active participation of cytotoxic lymphocytes in different clinical entities.
Our project aims to a better understanding of the immune mechanisms underlying the etiopathogenesis of these diseases. The study is performed in the framework of the consortium PIELenRed (Plataforma interdisciplinar para el estudio de reacciones cutáneas graves en red) integrated by researchers belonging to different hospitals in Madrid.
Reactivation of latent herpesvirus has been described during the development of some of the previously mentioned clinical entities. In order to improve our understanding of the behaviour of the immune system during viral replication, collaboration has been established with the Kidney Transplant Unit (Nephrology Service, HULP). Kidney transplant recipients are being followed immediately before and after transplant in order to identify patients with active CMV replication.

General objectives for the next 5 years
The objectives are:
i) Biobanking of samples of severe cutaneous adverse reactions to medications (DRESS, AGEP and SJS/TEN) associated to the registry PIELenRed, and integrated in the international registry RegiSCAR.
ii) To investigate in vitro test for drug causality assessement.
iii) To explore the involvement of the innate immune response (in particular natural cytotoxic activity ) during the development of SCARs.
iv) Identification of biomarkers of susceptibility .
v) To find biomarkers for disease and response to treatments.
vi) To explore the potential of microRNAs in SJS/TEN as biomarkers of disease and of response to treatments, as well as their relationship with pathogenic mechanisms.
vii) To analyze the evolution of the cytotoxic response in patients with CMV replication.
viii) Compare  the innate  immune response in patients with CMV replication after kidney transplant and in patients with SCARs.
Research Lines
• Biobanking of biological samples from patients with severe cutaneous adverse reactions to medications (DRESS, AGEP and SJS/TEN). 
• Development and evaluation of in vtro tests for drug causality assessment.
• Identification of biomarkers of susceptibility.
• Involvement of NK receptors in the etiopathogenesis of Stevens-Johnson syndrome /Toxic epidermal necrolysis (SJS/TEN).
• Differential analysis of the cytokine pattern involved in different SCARs (AGEP, DRESS and SJS/TEN).
• Analysis of miRNAs as biomarkers of disease and response to treatments.