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Copyright © 2001 GERMC. Tous droits réservés.

*1: Lancet* 2000 Jul 15;356(9225):203-8**
Refractory sprue, cœliac disease, and enteropathy-associated T-cell lymphoma. French Cœliac Disease Study Group. Cellier C, Delabesse E, Helmer C, Patey N, Matuchansky C, Jabri B, Macintyre E, Cerf-Bensussan N, Brousse N Department of Gastroenterology, Hopital Laennec, INSERM E9925, Paris, France. christophe.cellier@egp.ap-hop-paris.fr BACKGROUND: Adult refractory sprue is a poorly defined disorder. We did a multicentre national study of patients with refractory sprue to characterise their clinical and pathological profile and outcome, and to assess the frequency and prognostic significance of phenotypic and molecular abnormalities in the intraepithelial T-cell population. METHODS: Patients with severe symptomatic villous atrophy mimicking cœliac disease but refractory to a strict gluten-free diet, and with no initial evidence of overt lymphoma, were diagnosed at gastrointestinal referral centres between 1974 and 1998. Fixed and/or frozen duodenojejunal biopsy samples were reanalysed and immunostained with CD3 and CD8 monoclonal antibodies to find out the phenotype of intraepithelial lymphocytes (IEL). TCRgamma gene rearrangements were assessed on frozen biopsy samples by multiplex fluorescent PCR. FINDINGS: There were 21 patients with refractory sprue and 20 controls with cœliacs disease. 16 (84%) of 19 assessed patients had an aberrant intraepithelial lymphoid intestinal population expressing intracytoplasmic CD3 but not surface CD8. Clonal intestinal TCRgamma gene rearrangements were found in 13 (76%) of 17 patients assessed; four (out of 12 assessed) had clonal dissemination to the blood. The 16 patients with an aberrant phenotype all had uncontrolled malabsorption; three subsequently developed overt T-cell lymphoma, and eight died. The three (16%) patients without aberrant clonal IEL made a complete clinical and histological recovery with steroid therapy plus a gluten-free diet. INTERPRETATION: An immunophenotypically aberrant clonal intraepithelial T-cell population (similar to that of most cases of enteropathy-associated T-cell lymphoma) can be found in up to 75% of patients with refractory cœliac sprue; its identification by simple diagnostic techniques represents a marker of poor outcome (including occurrence of overt T-cell lymphoma). We suggest that refractory sprue associated with an aberrant clonal IEL may be the missing link between cœliac disease and T-cell lymphoma and may be classified as cryptic enteropathy-associated T-cell lymphoma. Publication Types: Multicenter study Comment in: Lancet. 2000 Jul 15;356(9225):178-9 PMID: 10963198
*2: Histopathology* 2000 Jul;37(1):70-7**
Distinction between cœliac disease and refractory sprue: a simple immunohistochemical method. Patey-Mariaud De Serre N, Cellier C, Jabri B, Delabesse E, Verkarre V, Roche B, Lavergne A, Briere J, Mauvieux L, Leborgne M, Barbier JP, Modigliani R, Matuchansky C, MacIntyre E, Cerf-Bensussan N, Brousse N Department of Pathology and Universite René Descartes-Paris V (EA 219), INSERM E 9925, Paris, France. AIMS: We recently showed that refractory sprue is distinct from cœliac disease, the former being characterized by abnormal intraepithelial T-lymphocytes expressing a cytoplasmic CD3 chain (CD3c), lacking CD3 and CD8 surface expression, and showing TCRgamma gene rearrangements. To take advantage of the abnormal phenotype of CD3c + CD8 - intraepithelial lymphocytes (IEL) in refractory sprue we developed a simple method to distinguish cœliac disease from refractory sprue. METHODS AND RESULTS: Comparative immunohistochemical studies using anti-CD3 and anti-CD8 antibodies were applied on paraffin-embedded and frozen biopsy specimens in refractory sprue (n = 6), cœliac disease (n = 10), healthy controls (n = 5) and suspected refractory sprue (n = 6). Comparable results were obtained on fixed and frozen biopsy specimens. In four of the six patients with suspected refractory sprue, abnormal CD3c + CD8 - IEL and TCRgamma gene rearrangements were found, as in refractory sprue; the remaining two patients had normal (CD3 + CD8 +) IEL and no TCRgamma gene rearrangements. Both patients had cœliac disease, as one failed to comply with a gluten-free diet, while the other was a slow responder. CONCLUSION: This simplified immunostaining method using anti-CD3 and anti-CD8 antibodies on paraffin sections can distinguish active cœliac disease from refractory sprue and should prove useful in clinical practice. PMID: 10931221
*3: Gastroenterol Clin Biol* 2000 Apr;24(4):436-46**
[Etiological diagnosis of villous atrophy]. [Article in French] Patey-Mariaud De Serre N, Verkarre V, Cellier C, Cerf-Bensussan N, Schmitz J, Brousse N Service d'Anatomie et de Cytologie Pathologiques, Centre Hospitalier, Le Raincy-Montfermeil. Publication Types: Review Review, tutorial PMID: 10844289
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