Mucosal Intraepithelial T-lymphocytes in Refractory Celiac Disease: A Neoplastic Population With a Variable CD8 Phenotype

Abstract

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 RCD 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 CD 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.

Continual monitoring of intraepithelial lymphocyte immunophenotype and clonality is more important than snapshot analysis in the surveillance of refractory coeliac disease

“…However, in a small proportion of biopsies, only one of the abnormalities was detected. Such inconsistency has been described 5 13 20 23. The lack of 100% sensitivity and specificity of these methodologies might be a cause for the inconsistency, but true non-concordance between IEL immunophenotype and clonality probably exists.…”

“…Similarly, T cell clonality analysis also has its limitations due to the oligoclonal nature of the T cell repertoire in the normal gut mucosa21 and use of non-standardised PCR primers and protocols in previous studies before the BIOMED-2 era 22. This may potentially account for the variable incidences of monoclonality and also the variable correlations between monoclonality and the aberrant immunophenotype in both CD and RCD groups from previous studies 6 7 11 20 23. Furthermore, most of the previous studies were a snapshot analysis of biopsies taken at a single time point or within a short period, and the natural course of IEL immunophenotypic and clonality changes during the disease progression from CD to RCD and EATL is poorly understood.…”

Immunohistochemical and T-Cell Receptor Gene Rearrangement Analyses as Predictors of Morbidity and Mortality in Refractory Celiac Disease

“…4,6 This CD3 À CD8 À phenotype (CD3 + CD8 À by immunohistochemistry) is frequently, but not always, associated with the presence of a monoclonal IEL population by TCR gene rearrangement analysis, as cases of RCD type II with a CD8 + IEL phenotype have been reported. [6][7][8] Analysis of IEL phenotype by immunohistochemistry and/or TCR gene rearrangement by PCR analysis has, therefore, become part of the diagnostic workup of RCD.…”

Aspects moléculaires des lymphomes T périphériques (2)

“…Il existe un continuum entre MCR de type II et LTAE. En effet, on détecte, au cours de l'évolution naturelle de la maladie, le même clone T aux stades de MCR II et de LTAE [94,97] + , quelques résultats suggèrent l'implication de la cellule souche hématopoïétique dans le processus de transformation tumorale. Dans un modèle de souris transgénique exprimant Tax, il a été en effet rapporté que les cellules souches leucémiques capables de propager la maladie dans des receveurs secondaires avaient un phénotype de progéniteur précoce ayant conservé ses capacités de différenciation en cellules lymphoïdes et myéloïdes [88].…”