Refractory coeliac sprue is a diffuse gastrointestinal disease.
BACKGROUND
Refractory coeliac sprue (RCS) with an immunophenotypically aberrant clonal intraepithelial lymphocyte (IEL) population is considered a cryptic form of intestinal T cell lymphoma.


OBJECTIVE
To investigate the distribution of the abnormal and monoclonal IEL population in the digestive tract of RCS patients.


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 gamma gene (TCR-gamma) 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-gamma 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.


CONCLUSIONS
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.
Verkarre
V
V
Department of Pathology and Université René Descartes-Paris V (EA219), AP-HP, Hôpital Necker-Enfants Malades, 75015 Paris, France. virginie.verkarre@nck.ap-hop-paris.fr
Asnafi
V
V
Lecomte
T
T
Patey Mariaud-de Serre
N
N
Leborgne
M
M
Grosdidier
E
E
Le Bihan
C
C
Macintyre
E
E
Cellier
C
C
Cerf-Bensussan
N
N
Brousse
N
N
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000276:immunology; D015703:Antigens, CD / Q000276:immunology; D002446:Celiac Disease / Q000276:immunology*; D003092:Colitis / Q000276:immunology; D003106:Colon / Q000276:immunology*; D005260:Female; D005753:Gastric Mucosa / Q000276:immunology*; D005756:Gastritis / Q000276:immunology; D015334:Gene Rearrangement, gamma-Chain T-Cell Antigen Receptor / Q000276:immunology; D006801:Humans; D007413:Intestinal Mucosa / Q000276:immunology; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D016133:Polymerase Chain Reaction / Q000379:methods; D011446:Prospective Studies; D013601:T-Lymphocytes / Q000276:immunology*
D000911:Antibodies, Monoclonal; D015703:Antigens, CD