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.

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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
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article

Incidence of malignancy after intestinal transplant

Nicola Colucci, Philip Allan, Neil Russell, Charlotte Yates et al.
Intestinal failure.
Metastasis and carcinoma case studies
article

Incidence of malignancy after intestinal transplant

Nicola Colucci, Philip Allan, Neil Russell, Charlotte Yates, Emilio Canovai, Charlotte Rutter, Tim Ambrose, Andrew Butler, Michael J. Fitzpatrick, Srikanth Reddy, Mahesh Polamreddy, Irum Amin, Venkatesha Udupa
article en

Abstract

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.

Intestinal failure.Vol. 6
Churchill Hospital (GB), Cambridge University Hospitals NHS Foundation Trust (GB), University of Oxford (GB)
Openalex Percentile: Top 66%
Metastasis and carcinoma case studies
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