title: Effect of elemental diet on mucosal immunopathology and clinical symptoms in type 1 refractory celiac disease.
abstract: OBJECTIVE
  Patients with celiac disease (CD) who do not improve or exhibit villous atrophy on a gluten-free diet may have type 1 refractory CD (RCD) with a polyclonal mucosal T-cell infiltrate, or type 2 RCD with a monoclonal infiltrate, also termed cryptic T-cell lymphoma. Both conditions are difficult to treat. Here we describe the effects of a nonimmunogenic elemental diet on clinical symptoms and mucosal immunopathology in type 1 RCD.
  
  
  METHODS
  Ten CD patients on a strict gluten-free diet were diagnosed with type 1 RCD after extensive clinical evaluation in a tertiary referral hospital. A 4-week amino-acid-based liquid elemental diet regimen was given with no other treatment, except in 1 patient who also received methotrexate. Duodenal biopsy specimens were obtained before and after treatment for histologic assessment, immunophenotyping of intraepithelial lymphocytes, T-cell receptor clonality, mucosal interleukin (IL)-15 expression, flow-cytometric analysis of interferon (IFN)-gamma-secreting T cells, and whole biopsy specimen IFN-gamma messenger RNA determination.
  
  
  RESULTS
  Nine patients completed the treatment; however, 1 patient did not tolerate the diet. Histologic improvement and reduced epithelial IL-15 were seen in 8 patients, whereas IFN-gamma-secreting mucosal T cells and IFN-gamma messenger RNA levels decreased in 4 and 7 patients, respectively. Clinical improvement was noted in 6 patients, with 1 patient showing normalization of hypoalbuminemia. Three patients could discontinue their total parenteral nutrition.
  
  
  CONCLUSIONS
  Persistent mucosal IFN-gamma and IL-15 production often occurs in type 1 RCD despite conventional treatment. Elemental diet is a therapeutic option that can provide long-term immunopathologic and clinical improvement of this difficult condition.
authors.affiliation: Laboratory for Immunohistochemistry and Immunopathology, Institute of Pathology, University of Oslo, Oslo, Norway.
authors.forename: Richard Willfred
authors.initials: RW
authors.lastname: Olaussen
authors.forename: Astrid
authors.initials: A
authors.lastname: Løvik
authors.forename: Stig
authors.initials: S
authors.lastname: Tollefsen
authors.forename: Per Arne
authors.initials: PA
authors.lastname: Andresen
authors.forename: Morten H
authors.initials: MH
authors.lastname: Vatn
authors.forename: Thomas
authors.initials: T
authors.lastname: De Lange
authors.forename: Jorunn
authors.initials: J
authors.lastname: Bratlie
authors.forename: Per
authors.initials: P
authors.lastname: Brandtzaeg
authors.forename: Inger Nina
authors.initials: IN
authors.lastname: Farstad
authors.forename: Knut E A
authors.initials: KE
authors.lastname: Lundin
mesh_terms: D000328:Adult; D000368:Aged; D001706:Biopsy; D015992:Body Mass Index; D017252:CD3 Complex / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D002446:Celiac Disease / Q000178:diet therapy* / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D018753:Diet, Protein-Restricted; D004386:Duodenum / Q000276:immunology / Q000473:pathology; D005260:Female; D005434:Flow Cytometry; D005526:Food, Formulated; D006801:Humans; D007150:Immunohistochemistry; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000378:metabolism; D019409:Interleukin-15 / Q000378:metabolism; D007413:Intestinal Mucosa / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009664:Norway; D012333:RNA, Messenger / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D017252:CD3 Complex; D019409:Interleukin-15; D012333:RNA, Messenger; D011948:Receptors, Antigen, T-Cell; D007371:Interferon-gamma