Single-Cell Analysis of Refractory Celiac Disease Demonstrates Inter- and Intra-Patient Aberrant Cell Heterogeneity
Tessa Dieckman, Mette Schreurs, Ahmed Mahfouz, Yvonne Kooy–Winkelaar, Andra Neefjes‐Borst, Gerd Bouma, Frits Koning
Abstract
BACKGROUND & AIMS: aberrant cell population. However, RCDII pathogenesis is ill-defined. Here, we aimed at single-cell characterization of the innate and adaptive immune system in RCDII. METHODS: Paired small intestinal and blood samples from 12 RCDII patients and 6 healthy controls were assessed by single-cell mass cytometry with a 39-cell surface marker antibody panel, designed to capture heterogeneity of the innate and adaptive immune system. A second single-cell mass cytometry panel that included transcription factors and immune checkpoints was used for analysis of paired samples from 5 RCDII patients. Single-cell RNA sequencing analysis was performed on duodenal samples from 2 RCDII patients. Finally, we developed a 40-marker imaging mass cytometry antibody panel to evaluate cell-cell interactions in duodenal biopsy specimens of RCDII patients. RESULTS: antigen-presenting cells (APCs) in situ. In addition, we observed phenotypic discrepancy between peripheral and duodenal aberrant cells. CONCLUSIONS: Novel high-dimensional single-cell technologies show substantial intertumoral and intratumoral heterogeneity in the aberrant cell population in RCDII. This may underlie variability in refractory disease status between patients and responsiveness to therapy, pointing to the need for personalized therapy in RCDII based on patient-specific immune profiles.