2013 Research Award Recipient
Principle Investigator: María Vicario Pérez, PhD
Senior Investigator
Digestive Diseases Research Unit
Hospital Vall d’Hebron
Barcelona, Spain
Dr. Vicario is senior researcher at the Vall d’Hebron Institut de Recerca, in Barcelona, Spain. She graduated in Pharmacy at Universidad Complutense de Madrid and received her Master’s degree in Physiology of the Gastrointestinal Tract, and her PhD in Pharmacy at the Universitat de Barcelona. She completed her four-year postdoctoral fellowship in Mucosal Immunology both in the Digestive Diseases Research Unit at Hospital Vall d’Hebron and in the Allergy and Immunology Unit in Cincinnati Children’s Hospital Medical Center, in Cincinnati, Ohio. Her research is focused on the study of neuro-immune mechanisms underlying gastrointestinal dysfunction as a potential nexus to prevalent diseases, associated with altered motility and hypersensitivity. She combines the study of esophageal inflammatory diseases and functional gastrointestinal disorders with academic and mentorship activities. She has recently been awarded the “2012 Rising Star Award” of the Spanish Society of Pathological Diseases.
Title: Distinctive humoral activity in the intestinal mucosa of IBS. New approach to IBS etiopathogenesis.
Background: Despite the high prevalence of irritable bowel syndrome (IBS), specific diagnostic procedures as well as efficacious therapies are lacking, accounting for an enormous economic impact for the society. Low-grade intestinal inflammation and abnormal immunological function are implicated in IBS pathophysiology. Most studies identify mast cells and T lymphocytes as the main populations accounting for the inflammatory infiltrate. Moreover, studies in our group have demonstrated the association between mast cells and structural abnormalities in the epithelial barrier, both related to the severity of symptoms.
Importantly, the intestine harbors the largest immunological organ in the body in terms of number of leukocytes and antibody production, being the humoral response a key element of the barrier function and intestinal homeostasis. However, in IBS, a disorder characterized by altered intestinal permeability and increased local immunological activity, the contribution of B lymphocytes has not been addressed. Interestingly, data from our group, indicate increased density of both B lymphocytes and plasma cells, the latter displaying closer proximity to nerve endings in the jejunal mucosa in diarrhoea-predominant IBS compared to controls. Although preliminary, molecular markers of class-switch recombination are highly expressed in the intestinal mucosa of patients and not in blood, suggesting increased local immune mechanisms in IBS.
Aims: To identify the contribution of B cells to the pathophysiology of IBS and characterize the intestinal Ig profile secreted, as well as the neuroimmune mechanisms promoting plasma cell survival and Ig production, in order to identify new disease mechanisms and design innovative therapeutic strategies for IBS.
Methods: We will obtain peripheral blood, jejunal aspirate, jejunal biopsies and feaces from IBS (Rome III criteria) and healthy volunteers, in which cellular and molecular components of the humoral response will be studied. Furthermore, we will study the association between biological findings and clinical symptoms (based on Rome III criteria). In parallel, neuro-immune mechanisms of Ig production will also be studied.