Refractory Celiac Disease

🧬 Refractory Celiac Disease (RCD): A Closer Look into Dysregulated T Cells

🔬 New Study Alert
Published in: Science Translational Medicine
Authors: Singh et al.
Key Insight: Chronic, treatment-resistant celiac disease is linked to T cells with lymphoma-associated mutations, revealing a potential therapeutic target.

❗ What is Refractory Celiac Disease?

• RCD1: Persistent symptoms without abnormal lymphoid cell infiltration.
• RCD2: Characterized by abnormal sCD3⁻ innate lymphoid cells in the gut lining.

🧫 What Did the Study Find?

Using multi-omic single-cell analysis of duodenal biopsies:

• ✅ RCD2 patients had sCD3⁻ lymphocytes with lymphoma driver mutations.
  • These cells are stuck in a T cell–ILC progenitor stage.
  • Showed active TCR recombination (TRA, TRB, TRD).
• ✅ RCD1 patients had sCD3⁺ T cells with similar lymphoma-associated mutations.
  • Found in 6 of 10 RCD1 patients.
  • Also found in 1 newly diagnosed celiac disease patient.
  • These mutant T cells formed large, clonal TCRαβ expansions.
  • Showed inflammatory & cytotoxic profiles.

💡 Implications

• RCD1, previously considered idiopathic, may also involve neoplastic T cell populations.
• Lymphoma driver mutations in both RCD1 and RCD2 suggest:
  • A shared pathogenic mechanism.
  • Potential for targeted therapy against these dysregulated T cells.

🧠 Editor’s Summary (Courtney Malo)

“These data provide a landscape of RCD1 and RCD2 and suggest that these T cells with lymphoma driver mutations may represent a therapeutic target.”

Source: https://www.science.org/doi/10.1126/scitranslmed.adp6812