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Seminars in Immunopathology

, Volume 34, Issue 4, pp 601–613 | Cite as

Refractory celiac disease: from bench to bedside

  • Georgia Malamut
  • Bertrand Meresse
  • Christophe Cellier
  • Nadine Cerf-BensussanEmail author
Review

Abstract

Refractory celiac disease is defined by the persistence of symptoms of malnutrition and intestinal villous atrophy for more than 6–12 months despite strict gluten-free diet in celiac patients. Diagnosis of this rare condition is made after excluding other causes of chronic small intestinal inflammation and villous atrophy and inadvertent intake of gluten. Over the past 15 years, multidisciplinary approaches have been developed to assess the mechanism of resistance to the diet, and two distinct entities have been delineated. Type II refractory celiac disease (RCD) can be defined as a low-grade intraepithelial lymphoma. RCD II is characterised by a massive accumulation of abnormal IEL that display an aberrant hybrid NK/T cell phenotype, contain clonal T cell rearrangement(s) and can mediate a cytolytic attack of the gut epithelium. This condition has a severe prognosis, largely due to the frequent transformation of RCDII IEL into overt aggressive enteropathy-type-associated T cell lymphoma. In contrast, in type I RCD, intestinal lymphocytes have a normal phenotype, and this generally milder condition remains often difficult to differentiate from uncomplicated CD except for the resistance to gluten-free diet (GFD). Several mechanisms may underlie resistance to gluten. Herein, we review the distinctive characteristics of RCD I and RCD II, the mechanisms underlying the onset of resistance to GFD, the risk of developing high grade lymphoma and possible clues to improve their treatment.

Keywords

Celiac disease Intraepithelial lymphocytes Colllagenous sprue Enteropathy-type-associated lymphoma Gluten 

Notes

Acknowledgements

The authors acknowledge funding from INSERM, Ligue Contre le Cancer, Fondation Pour la Recherche Médicale, Agence Nationale pour la Recherche, Association pour la Recherche contre le Cancer, Association française des Patients Intolérants au Gluten, Fondation Princesse Grace. They thank all members of INSERM U989 for sharing work and helpful discussions. They also thank members of GERMC and CELAC for providing samples and sharing data from their patients as well as for helpful discussions.

Authors declare no conflict of interest

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Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • Georgia Malamut
    • 1
    • 2
    • 3
  • Bertrand Meresse
    • 1
    • 2
  • Christophe Cellier
    • 1
    • 2
    • 3
  • Nadine Cerf-Bensussan
    • 1
    • 2
    • 4
    Email author
  1. 1.INSERM, U989ParisFrance
  2. 2.Institut IMAGINEUniversité Paris Descartes and Paris Sorbonne CitéParisFrance
  3. 3.APHP Gastroenterology departmentHôpital Européen Georges PompidouParisFrance
  4. 4.Université Paris Descartes, Inserm U989ParisFrance

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