Oral Presentation International Celiac Disease Symposium 2026

Combined immunophenotyping reveals disease-stage-related patterns of gluten-specific CD4+ T cells and TG2-specific plasma cells in potential, untreated and treated celiac disease (145920)

Jørgen Jahnsen 1 , Knut EA Lundin 2 3 , Ludvig M Sollid 2 4 , Louise Fremgaard Risnes 2 4 5
  1. Department of Gastroenterology, Akershus University Hospital, Lørenskog, Norway
  2. Norwegian Coeliac Disease Research Centre, University of Oslo, Oslo, Norway
  3. Department of Gastroenterology, Oslo University Hospital, Oslo, Norway
  4. Department of Immunology, Oslo University Hospital, Oslo, Norway
  5. Department of Gastroenterology, Oslo University Hospital, Oslo, Norway

Background: Gluten-specific CD4+ T cells and transglutaminase 2 (TG2)-specific plasma cells (PCs) are central components of celiac disease (CeD) pathogenesis. Both cell types are readily detected in untreated CeD (UCeD) and treated (TCeD) subjects. Whether the cells are present in potential CeD (PCeD; positive IgA-TG2 and/or IgG-DGP, Marsh 0/1) is less known.

Materials and methods: By flow cytometry, we combined HLA-DQ2.5:gluten-tetramers and TG2-tetramers to immunophenotype single-cell suspensions of duodenal biopsies of PCeD, UCeD, TCeD and control subjects (Table1). An HLA-DQ2.5:gluten-tetramer test that distinguishes CeD from healthy controls (PMID:29146521) was applied to available blood samples.  

Results: Frequencies of TG2-specific PCs in tissue were above controls for PCeD albeit lower than for UCeD and TCeD (Table1). Frequencies of gluten-specific CD4+ T-cells in tissue were more comparable to controls except for two subjects. These two subjects scored positive for the HLA-DQ2.5:gluten-tetramer test, whereas 3/6 PCeD and 4/4 controls scored negative. Intestinal gluten-specific CD4+ T cells of UCeD were phenotypically distinct from TCeD. PCeD showed variable marker expressions with the largest difference from UCeD in expression of CD39. One PCeD subject developed CeD within 3 years, coinciding with rising IgA-TG2 levels and frequencies of TG2-specific PCs (2.4% to 8.3%) and gluten-specific CD4+ T cells (0.09% to 0.54%), alongside a positive HLA-DQ2.5:gluten-tetramer test. For another PCeD subject followed longitudinally, the frequencies of tissue TG2-specific PCs (1.7% to 2.8%) and gluten-specific CD4+ T cells (from 0.06% to 0.16%) remained fairly stable. The blood HLA-DQ2.5:gluten-tetramer test converted to negative and with serum IgA-TG2 levels being slightly elevated.

Conclusions: In PCeD, intestinal TG2-specific PCs are present at frequencies higher than observed for control subjects while this was not the case for gluten-specific CD4+ T cells. The findings suggest that disease development may depend on a critical presence of gluten-specific CD4+ T cells, particularly in the gut tissue.

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