Refractory coeliac sprue is a diffuse gastrointestinal disease

• Published in: Gut 2003-02, Vol.52 (2), p.205-211
• Main Authors: Verkarre, V, Asnafi, V, Lecomte, T, Mariaud-De Serre, N Patey, Leborgne, M, Grosdidier, E, Le Bihan, C, Macintyre, E, Cellier, C, Cerf-Bensussan, N, Brousse, N
• Format: Article
• Language: English
• Subjects: ACD; active coeliac disease; Adult; Aged; Antibodies, Monoclonal - immunology; Antigens, CD - immunology; CD on a GFD; Celiac disease; Celiac Disease - immunology; Coeliac Disease; Colitis - immunology; Colon; Colon - immunology; EITCL; enteropathy-type intestinal T cell lymphoma; Female; Gastric Mucosa - immunology; Gastritis - immunology; Gastrointestinal diseases; Gene Rearrangement, gamma-Chain T-Cell Antigen Receptor - immunology; Genotype & phenotype; GFD; GFD-CD; Gluten; gluten free diet; Humans; IEL; Immunoglobulins; Intestinal Mucosa - immunology; intraepithelial lymphocyte; Lymphocyte Count; Lymphocytes; lymphocytic colitis; lymphocytic gastritis; Lymphoma; Male; Middle Aged; Nutrition research; Patients; PCR; Phenotype; polymerase chain reaction; Polymerase Chain Reaction - methods; Population; Prospective Studies; RCS; refractory coeliac sprue; refractory sprue; Rodents; Small intestine; Studies; T cell lymphoma; T cell receptor; T cell receptor gene rearrangement; T cell receptors; T-Lymphocytes - immunology; TCR
• ISSN: 0017-5749; 1468-3288; 1458-3288
• DOI: 10.1136/gut.52.2.205

Background: Refractory coeliac sprue (RCS) with an immunophenotypically aberrant clonal intraepithelial lymphocyte (IEL) population is considered a cryptic form of intestinal T cell lymphoma. Aims: To investigate the distribution of the abnormal and monoclonal IEL population in the digestive tract of RCS patients. Patients and methods: We compared the frequency of lymphocytic gastritis (LG) and lymphocytic colitis (LC), together with IEL phenotype and T cell clonality, in gastric and colonic samples from 15 adults with RCS (all with aberrant CD3 intracytoplasmic+ surface− CD8− clonal IELs on duodenojejunal biopsies), 18 patients with active coeliac disease (ACD), and 10 patients with coeliac disease (CD) on a gluten free diet (GFD-CD) by means of immunohistochemistry and multiplex polymerase chain reaction amplification of the T cell receptor γ gene (TCR-γ) rearrangement. Blood samples of nine RCS patients were also tested for clonality. Results: LG was found in 9/14 (64%), 11/18 (61%), and 3/10 (30%) patients with RCS, ACD, and GFD-CD, respectively, while LC was found in 6/11 (55%), 3/4 (75%), and 2/3 (66%) patients. Contrary to CD, all samples from patients with LG and LC showed an aberrant IEL phenotype. Monoclonal TCR-γ rearrangements were detected in 8/13 (62%), 8/10 (80%), and 4/9 (44%) of gastric, colonic, and blood samples, respectively, from RCS patients, while in CD patients such rearrangements were only found in 2/25 (8%) gastric samples. Conclusion: The immunophenotypically aberrant monoclonal IEL population present in the small intestine of patients with RCS frequently disseminates to the blood and the entire gastrointestinal epithelium, suggesting that this is a diffuse gastrointestinal disease.