GUT IMMUNOLOGY

Heterogeneity of intraepithelial lymphocytes in refractory sprue: potential implications of CD30 expression

I N Farstad¹, F-E Johansen¹, L Vlatkovic², J Jahnsen³, H Scott⁴, O Fausa⁵, A Bjørneklett⁵, P Brandtzaeg⁶, T S Halstensen⁷

¹ Department of Pathology, and Laboratory for Immunohistochemistry and Immunopathology (LIIPAT), Institute of Pathology, University of Oslo, Rikshospitalet, Oslo, Norway
² Department of Pathology, Aker University Hospital, Oslo, Norway
³ Medical Department, Aker University Hospital, Oslo, Norway
⁴ Department of Pathology, Institute of Pathology, University of Oslo, Rikshospitalet, Oslo, Norway
⁵ Medical department, University of Oslo, Rikshospitalet, Oslo, Norway
⁶ Laboratory for Immunohistochemistry and Immunopathology (LIIPAT), Institute of Pathology, University of Oslo, Rikshospitalet, Oslo, Norway
⁷ Laboratory for Immunohistochemistry and Immunopathology (LIIPAT), Institute of Pathology, and Institute of Oral Biology, University of Oslo, Rikshospitalet, Oslo, Norway

Correspondence to:
Correspondence to:
Dr I N Farstad, Institute of Pathology, Rikshospitalet, N-0027 Oslo, Norway;
i.n.farstad{at}labmed.uio.no

Background: Refractory sprue is defined as primary or secondary failure to respond to a gluten free diet in patients with coeliac disease-like enteropathy and may signify cryptic or overt enteropathy associated T cell lymphoma.

Aims: To study in detail jejunal morphology and immunophenotypes in patients with refractory sprue in the search for features that might be useful to predict prognosis.

Patients: Seven patients are described, representing all such cases identified in our hospital over a 13 year period.

Methods: Biopsy and/or surgical resection specimens were examined by morphology, immunohistochemistry, including enzymatic and immunofluorescent detection, and molecular biology.

Results: All patients had phenotypically abnormal intraepithelial lymphocytes (IELs) that lacked CD8, T cell receptor ß (or ), and/or expressed CD30 in addition to variable expression of the natural killer cell receptor CD94. A monoclonal T cell population was present in six cases, data from the seventh being inconclusive. Three patients had overt lymphoma with CD30+ tumour tissue intervening between intact mucosa that contained neoplastic IELs. Intriguingly, CD30+ IELs were observed both a long way away from, and in direct continuity with, the tumours in these patients. Such CD30+ cells were hardly detected in patients without tumours, two of which are in good health several years after the initial diagnosis.

Conclusions: Our data suggest that abnormal IELs in patients with refractory sprue are phenotypically heterogeneous. CD30 expression by these cells may indicate a worse prognosis, including the occurrence of overt lymphoma.

Keywords: refractory sprue; immunohistochemistry; intraepithelial lymphocytes; CD30; T cell lymphoma; enteropathy

Abbreviations: AGA, antigliadin antibodies; GFD, gluten free diet; EATL, enteropathy associated T cell lymphoma; EBV, Epstein-Barr virus; EMA, endomysial antibodies; IELs, intraepithelial lymphocytes; LCA, leucocyte common antigen; mAbs, monoclonal antibodies; PCR, polymerase chain reaction; TCR, T cell receptor

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