Complicated adult Celiac Disease

Principal Investigator: Professor Corazza G.R., First Department of Medicine, Fondazione IRCCS Policlinico S. Matteo, University of Pavia, Pavia, Italy


The natural history of complicated celiac disease is not well known. In some cases that are diagnosed late in adult age, the disease presents right from the start with complications (refractory celiac disease, ulcerative jejunoileitis, collagenous sprue and enteropathy-associated T-cell lymphoma). According to the data collected while carrying out this project, the prevalence of complicated celiac disease in Italy is around 0.75%. Complication predictors include diagnosis after the age of 50, a delay between onset of symptoms and diagnosis of more than 10 years, typical symptoms (frank malabsorption syndrome) and the presence of HLA-DQ2 homozygosis. On the basis of the diagnostic delay and the clinical presentation, the Pavia research group has constructed a mathematical model which makes it possible to estimate the risk and possible progression towards the complicated for of celiac disease. The study has also made it possible to define a number of aspects, about which little was formerly known, of the immunological pathogenetic mechanisms that underlie the complications of celiac disease, such as the role of the CD40/CD40L system which at mucosal level amplifies the inflammatory response by triggering an interaction between lymphocytes and antigen-presenting cells. Another important objective of the project is verification of the involvement of certain viruses, generally associated with the development of some tumors, in the natural history of complicated celiac disease. The presence of these viruses was therefore evaluated in the intestinal biopsies taken from 18 patients with complicated celiac disease and 26 patients with non-complicated celiac disease, by means of a highly sensitive method, named PCR, which can be used to detect the specific genomic sequences of the viruses. The study showed that 72% of the patients with complicated celiac disease tested positive for the presence of the Epstein-Barr virus, a significantly higher fraction compared to patients with non-complicated celiac disease (15.3%). In conclusion, the Epstein-Barr virus seems to have a role in the progression of celiac disease towards complicated forms, representing a basis for designing new studies into the mechanisms of the onset of complications in some subjects with celiac disease. The project also obtained encouraging preliminary results on the use of mesenchymal stem cells in regulating gliadin-specific T lymphocytes, i.e. the immune system cells involved in the intestinal inflammatory process induced by gluten. This result therefore provides a basis for the development of potential treatments of refractory celiac disease by means of the use of stem cells.


Publications Related to the FC Grant:

  1. Vittorio Perfetti, Laura Brunetti, Federico Biagi, et al TCRb clonality improves diagnostic yield of TCRg clonality in refractory coeliac disease. J Clin Gastroenterol 2012; in press.
  2. Di Sabatino A, Rovedatti L, Vetrano S, et al Involvement of CD40-CD40 ligand in uncomplicated and refractory celiac disease. Am J Gastroenterol 2011;106:519-27.
  3. Biagi F, Bianchi PI, Vattiato C, et al. The influence of HLA-DQ2 and DQ8 on severity in celiac disease. J Clin Gastroenterol 2012;46:46-50
  4. Ciccocioppo R, Russo ML, Bernardo ME, et al. Mesenchymal stromal cell infusions as rescue therapy in an adult with autoimmune enteropathy. Mayo Clinic Proceedings, in press.
  5. Ciccocioppo R, Bernardo ME, Russo ML, et al Hematopoietic stem cell transplantation restores gluten tolerance in celiac disease. Submitted for publication