Incidence of malignancy after intestinal transplant
control patients (NC).Bulk mRNA was extracted from mucosal samples.Paneth cells were analyzed histologically with HALO-AI.Data were analyzed on SAS, GraphPad Prism, R, nSolver, and PantherGO.Results: Compared to NC, CD specimens had acute inflammation and increased expression of inflammatory markers (IMs) and antimicrobial peptides (AMPs) by neutrophils (calprotectin p=0.006 and myeloperoxidase p<0.001) and Paneth cells (lysozyme p=0.001).In contrast, rejection specimens had minimal inflammatory infiltrate and no increase in IM/AMP expression.Correspondingly, Paneth cells were increased in CD (p<0.001) but decreased during rejection (p<0.001),coinciding with increased IFNg (p=0.021) (Fig. 1), which is known to be associated with Paneth cell loss.Pathway analysis showed increased Th1associated cytokines (CXCL9, CXCL10, CCL19) and less Th17associated cytokines (CCL20, IL1B, CCR4) and neutrophil chemotaxis pathways (CXCL2, CXCL5) during rejection, suggesting an immune response distinct from CD (Fig. 2).Conclusions: Our findings suggest different mucosal immune responses in ITx vs CD.While ITx rejection is characterized by a Th1-polarized immune response and IFNg-associated loss of Paneth cells and their products, CD is characterized by neutrophilic infiltrate, Th17-polarized immune response, and increased Paneth cells and their products.These findings provide insight for future diagnostic and therapeutic modalities.
Authors
- Nicola Colucci (ORCID: https://orcid.org/0000-0003-4939-981X)
- Philip Allan (ORCID: https://orcid.org/0000-0003-2682-772X)
- Neil Russell (ORCID: https://orcid.org/0000-0002-3265-4514)
- Charlotte Yates (ORCID: https://orcid.org/0000-0002-6431-4506)
- Emilio Canovai (ORCID: https://orcid.org/0000-0003-4921-466X)
- Charlotte Rutter (ORCID: https://orcid.org/0000-0003-1056-5841)
- Tim Ambrose (ORCID: https://orcid.org/0000-0001-9286-7485)
- Andrew Butler (ORCID: https://orcid.org/0000-0002-3031-3492)
- Michael J. Fitzpatrick
- Srikanth Reddy
- Mahesh Polamreddy
- Irum Amin
- Venkatesha Udupa
Institutions
- Churchill Hospital (GB)
- Cambridge University Hospitals NHS Foundation Trust (GB)
- University of Oxford (GB)
Publication Details
- Journal
- Intestinal failure.
- Published
- 2025-01-01
- DOI
- https://doi.org/10.1016/j.intf.2025.100130
- Primary Topic
- Metastasis and carcinoma case studies
- Type
- article
- Field-Weighted Citation Impact
- 0.00