title: Heat shock protein-derived T-cell epitopes contribute to autoimmune inflammation in pediatric Crohn's disease.
abstract: Pediatric Crohn's disease is a chronic auto inflammatory bowel disorder affecting children under the age of 17 years. A putative etiopathogenesis of Crohn's disease (CD) is associated with disregulation of immune response to antigens commonly present in the gut microenvironment. Heat shock proteins (HSP) have been identified as ubiquitous antigens with the ability to modulate inflammatory responses associated with several autoimmune diseases. The present study tested the contribution of immune responses to HSP in the amplification of autoimmune inflammation in chronically inflamed mucosa of pediatric CD patients. Colonic biopsies obtained from normal and CD mucosa were stimulated with pairs of Pan HLA-DR binder HSP60-derived peptides (human/bacterial homologues). The modulation of RNA and protein levels of induced proinflammatory cytokines were measured. We identified two epitopes capable of sustaining proinflammatory responses, specifically TNF< and IFN induction, in the inflamed intestinal mucosa in CD patients. The responses correlated positively with clinical and histological measurements of disease activity, thus suggesting a contribution of immune responses to HSP in pediatric CD site-specific mucosal inflammation.
authors.affiliation: Department of Medicine/Pediatrics, University of California San Diego, La Jolla, California, United States of America.
authors.forename: Gisella L
authors.initials: GL
authors.lastname: Puga Yung
authors.forename: Meredith
authors.initials: M
authors.lastname: Fidler
authors.forename: Erika
authors.initials: E
authors.lastname: Albani
authors.forename: Naomi
authors.initials: N
authors.lastname: Spermon
authors.forename: Gijs
authors.initials: G
authors.lastname: Teklenburg
authors.forename: Robert
authors.initials: R
authors.lastname: Newbury
authors.forename: Nicole
authors.initials: N
authors.lastname: Schechter
authors.forename: Theo
authors.initials: T
authors.lastname: van den Broek
authors.forename: Berent
authors.initials: B
authors.lastname: Prakken
authors.forename: Rosario
authors.initials: R
authors.lastname: Billetta
authors.forename: Ranjan
authors.initials: R
authors.lastname: Dohil
authors.forename: Salvatore
authors.initials: S
authors.lastname: Albani
mesh_terms: D000293:Adolescent; D015551:Autoimmunity; D018834:Chaperonin 60 / Q000737:chemistry; D002648:Child; D002675:Child, Preschool; D003424:Crohn Disease / Q000276:immunology*; D016207:Cytokines / Q000378:metabolism; D018984:Epitopes, T-Lymphocyte / Q000737:chemistry*; D005260:Female; D006360:Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D007249:Inflammation; D008297:Male; D010641:Phenotype
chemical_list: D018834:Chaperonin 60; D016207:Cytokines; D018984:Epitopes, T-Lymphocyte; D006360:Heat-Shock Proteins