Effect of elemental diet on mucosal immunopathology and clinical symptoms in type 1 refractory celiac disease

Clin Gastroenterol Hepatol. 2005 Sep;3(9):875-85. doi: 10.1016/s1542-3565(05)00295-8.


Background & aims: 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.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Biopsy
  • Body Mass Index
  • CD3 Complex / metabolism
  • CD8-Positive T-Lymphocytes / metabolism
  • Celiac Disease / diet therapy*
  • Celiac Disease / immunology
  • Celiac Disease / metabolism
  • Celiac Disease / pathology*
  • Diet, Protein-Restricted
  • Duodenum / immunology
  • Duodenum / pathology
  • Female
  • Flow Cytometry
  • Food, Formulated*
  • Humans
  • Immunohistochemistry
  • Immunophenotyping*
  • Interferon-gamma / metabolism
  • Interleukin-15 / metabolism
  • Intestinal Mucosa / immunology*
  • Intestinal Mucosa / metabolism
  • Intestinal Mucosa / pathology*
  • Male
  • Middle Aged
  • Norway
  • RNA, Messenger / metabolism
  • Receptors, Antigen, T-Cell / metabolism
  • T-Lymphocytes / metabolism
  • Treatment Outcome


  • CD3 Complex
  • Interleukin-15
  • RNA, Messenger
  • Receptors, Antigen, T-Cell
  • Interferon-gamma