Gastroenterology

Gastroenterology

Volume 114, Issue 3, March 1998, Pages 471-481
Gastroenterology

Alimentary Tract
Abnormal intestinal intraepithelial lymphocytes in refractory sprue,☆☆

https://doi.org/10.1016/S0016-5085(98)70530-XGet rights and content

Abstract

Background & Aims: The etiology of refractory sprue is unclear. To gain insight into its pathogenesis, the phenotype and T-cell receptor (TCR) gene rearrangement status of intestinal lymphocytes were analyzed in a group of patients with clinical or biological features of celiac disease but either initially or subsequently refractory to a gluten-free diet. Methods: Intestinal biopsy specimens were obtained from 26 adults: 6 patients with refractory sprue, 7 patients with active celiac disease, and 13 normal controls. The phenotype of intestinal lymphocytes was studied by immunohistochemistry and, in 3 patients with refractory sprue, by cytometry of lymphocytes purified from intestinal biopsy specimens. TCR rearrangements were assessed by studying TCRγV-J junctional regions from DNA extracted from intestinal biopsy specimens and purified intestinal lymphocytes. Results: In the 6 patients with refractory sprue, but not in normal controls or patients with active celiac disease, the intestinal epithelium was massively infiltrated by small lymphocytes that lacked CD8, CD4, and TCR, contained intracytoplasmic but not surface CD3ϵ chains, and exhibited restricted TCRγ gene rearrangements. Conclusions: Refractory sprue is associated with an abnormal subset of intraepithelial lymphocytes containing CD3ϵ and restricted rearrangements of the TCRγ chain but lacking surface expression of T-cell receptors.

GASTROENTEROLOGY 1998;114:471-481

Section snippets

Patients with refractory sprue

Six consecutive female adult patients with refractory sprue were studied (group I, Table 1).

. Characteristics of patients with refractory sprue

Empty CellEmpty CellEmpty CellEmpty CellAntibodiesEmpty CellEmpty Cell
UPN (sex)Age at onset (yr)Presenting symptomsAssociated featuresAEAGSubsequent response to a GFDOutcome
1070 (F)46Weight loss, diarrhea, abdominal painSister with GFD-sensitive CDa+Partial response to GFD for 6 mo only; steroid responsiveAlive 5 yr after diagnosis; steroid dependent
Ulcerative jejunitis
1398 (F)46Diarrhea, malnutrition

Histological results

Sequential duodenal biopsy specimens for standard histology were available for review over a period of 5–12 years for 4 patients and a period of 1–2 years in the 2 other patients. In all patients, total (grade IV) to subtotal (grade III) villous atrophy was present in approximately more than two thirds of the intestinal mucosa examined (Figure 1A), whereas areas with partial villous atrophy were present in the remaining mucosa (Figure 1B).

. Histology and immunohistochemistry in 1 patient with

Discussion

This study provides evidence that patients with unclassified or refractory sprue may be differentiated from celiac disease by the partial or almost complete disappearance of normal subsets of IELs and their replacement by morphologically normal but phenotypically abnormal lymphocytes, which express intracytoplasmic CD3ϵ but not surface CD3ϵ, TCR, CD4, or CD8 and demonstrate restricted rearrangements of the TCRγ gene.

All patients fulfilled the criteria of refractory sprue described by Trier1, 2

Acknowledgements

The authors thank Pr. S. Chaussade (Department of Gastroenterology, Hôpital Cochin, Paris) for providing biopsy specimens from controls; Pr. B. Messing and Pr. C. Matuchansky (Department of Gastroenterology, Hôpital Saint Lazare, Paris) for providing data from 1 patient; Dr. F. Carnot (Department of Pathology, Hôpital Laënnec, Paris) for providing histological specimens; Dr. O. Hermine (Department of Hematology, Hôpital Necker, Paris), Pr. C. Matuchansky (Department of Gastroenterology, Hôpital

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    Address requests for reprints to: Christophe Cellier, Ph.D., Service de Gastroentérologie, Hôpital Laënnec, 42 rue de Sèvres, 75007 Paris, France. Fax: (33)1-4439-6812.

    ☆☆

    Supported by INSERM, the Assistance Publique des Hôpitaux de Paris (PHRC P960906), and the Fondation de France.

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