title: Immunopathogenesis of olmesartan-associated enteropathy.
abstract: BACKGROUND
  Olmesartan-associated enteropathy (OAE) is characterised by diarrhoea, nausea, vomiting, abdominal pain, weight loss and severe sprue-like enteropathy, all of which are resolved after discontinuation of olmesartan medoximil.
  
  
  OBJECTIVE
  To determine the mechanistic similarities of OAE with coeliac sprue.
  
  
  METHODS
  Duodenal biopsies were extracted from OAE patients before (n = 11) or after (n = 17) discontinuation of olmesartan medoxomil (on or off olmesartan medoxomil). There were seven 'on/off' paired samples. Formalin-fixed biopsies were stained for CD8, CD4, FoxP3, IL-15R and psmad 2/3. Caco2 cells (human colonic epithelial line) were treated with olmesartan medoxomil and stained for IL-15, IL-15R and ZO-1.
  
  
  RESULTS
  In the 'on olmesartan medoxomil' duodenal biopsies, a significant increase in the numbers of CD8+ cells and the number of cells that are FoxP3+ (a regulatory T-cell marker) are present in the duodenum as compared to the duodenal biopsies from patients who discontinued olmesartan medoxomil. IL15R expression is also increased with olmesartan medoxomil use. Evaluation of the effect of olmesartan medoxomil upon Caco-2 cells demonstrated that IL15 expression is increased in response to olmesartan medoxomil treatment. Further, ZO-1, a tight junction protein, is disrupted in olmesartan medoxomil-treated Caco-2 cells.
  
  
  CONCLUSIONS
  Olmesartan-associated enteropathy shares many features with coeliac disease, including symptoms and immunopathogenic pathways, such as increased numbers of CD8+ cells and corresponding overexpression of IL15 by epithelial cells. Taken together, the treatment of epithelial cells with olmesartan medoxomil induces a response by intestinal epithelial cells that is similar to the innate effects of gluten upon the epithelium of coeliac patients.
authors.affiliation: Department of Immunology, Mayo Clinic, Rochester, MN, USA.|Department of Dermatology, Mayo Clinic, Rochester, MN, USA.|Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA.
authors.forename: E V
authors.initials: EV
authors.lastname: Marietta
authors.affiliation: Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA.
authors.forename: A M
authors.initials: AM
authors.lastname: Nadeau
authors.affiliation: Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA.
authors.forename: A K
authors.initials: AK
authors.lastname: Cartee
authors.affiliation: Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA.
authors.forename: I
authors.initials: I
authors.lastname: Singh
authors.affiliation: Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA.
authors.forename: A
authors.initials: A
authors.lastname: Rishi
authors.affiliation: Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA.
authors.forename: R S
authors.initials: RS
authors.lastname: Choung
authors.affiliation: Department of Anatomic Pathology, Mayo Clinic, Rochester, MN, USA.
authors.forename: T-T
authors.initials: TT
authors.lastname: Wu
authors.affiliation: Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA.
authors.forename: A
authors.initials: A
authors.lastname: Rubio-Tapia
authors.affiliation: Department of Immunology, Mayo Clinic, Rochester, MN, USA.|Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA.
authors.forename: J A
authors.initials: JA
authors.lastname: Murray
mesh_terms: D015746:Abdominal Pain / Q000209:etiology*; D001706:Biopsy; D018938:Caco-2 Cells; D002446:Celiac Disease / Q000175:diagnosis; D003967:Diarrhea / Q000139:chemically induced*; D004386:Duodenum / Q000187:drug effects* / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D009325:Nausea / Q000139:chemically induced; D000068557:Olmesartan Medoxomil / Q000009:adverse effects*; D050378:T-Lymphocytes, Regulatory / Q000378:metabolism; D014839:Vomiting / Q000139:chemically induced
chemical_list: D000068557:Olmesartan Medoxomil