Objective: Aberrant immunophenotype and monoclonality of intraepithelial lymphocytes (IEL) are frequently found in refractory celiac disease (RCD). However, the utility of continual monitoring of IEL immunophenotype and clonality in the surveillance of RCD remains to be studied.
Design: The diagnostic and follow-up biopsies from 33 CD, 7 suspected RCD, 41 RCD and 20 enteropathy associated T-cell lymphoma (EATL) (including 11 evolved from RCD) patients were investigated by CD3e/CD8 double immunohistochemistry and PCR-based clonality analysis of the rearranged TCR genes.
Results: An aberrant immunophenotype (CD3ϵ+CD8- IEL ≥40%) and monoclonality were detected occasionally in CD biopsies, either transiently in CD patients not compliant with a gluten free diet or in those who subsequently developed suspected RCD, RCD or EATL. In contrast, the aberrant immunophenotype and monoclonality were respectively found in 30 of 41 (73%) and 24 of 37 (65%) biopsies at the time of RCD diagnosis. Among the RCD patients who did not show these abnormalities in their diagnostic biopsies, 8 of 10 (80%) and 5 of 11 (45%) cases gained aberrant immunophenotype and monoclonality respectively during follow-up. Irrespective of whether detected in diagnostic or follow-up biopsies, persistence of both abnormalities was characteristic of RCD. Importantly, the presence of concurrent persistent monoclonality and aberrant immunophenotype, especially <≥>80% CD3ϵ+CD8- IEL, was a strong predictor of EATL development in RCD patients (P=0.001).
Conclusions: Continual monitoring of both immunophenotype and clonality of IEL is more important than snapshot analysis for RCD diagnosis and follow-up, and could provide a useful tool for surveillance of patients at risk of EATL.