Mucosal intraepithelial T-lymphocytes in refractory celiac disease:: A neoplastic population with a variable CD8 phenotype

Celiac disease (CD) is characterized by villous atrophy and an increase in intraepithelial lymphocytes (IEL). The IEL usually exhibit a suppressor/cytotoxic phenotype (CD3(+) and CD8(+)) and display a polyclonal profile for T-cell receptor (TCR) rearrangement as opposed to the monoclonality of refractory CD (RCD) with CD8(-) IEL. A complication of CD is the loss of response to a gluten-free diet called RCD that may progress to an enteropathy-associated T-cell lymphoma. We reviewed 20 uncomplicated CD and 23 complicated CD (19 RED and 4 diagnosed at the same time as enteropathy-associated T-cell lymphoma). In complicated CD, the IEL phenotype was CD8(-) in 9 cases and CD8(+) in 14 cases. In 100% of cases, IEL showed a monoclonal TCR rearrangement. All the 9 CD8(-) complicated CD exhibited a monoclonal TCR rearrangement and 3 of them were associated with a T-cell lymphoma (2 at the same time as CD and 1 after 43-mo follow-up) and bore the same monoclonal rearrangement in IEL and in lymphoma. Interestingly, the 13 cases (100%) of CID with a CD8(+) phenotype were also found monoclonal and 2 of them were associated with a T-cell lymphoma diagnosed at the same time as CD and exhibiting the same rearrangement in IEL and in lymphoma. An aberrant CD3(+) CD8(-) IEL phenotype is a good criterion for RCD diagnosis. However, cases with a normal CD3(+) CD8(+) IEL phenotype may correspond to RCD. In such cases, we suggest that molecular analysis of TCR-gamma genes is a useful method for identifying cases with RCD.