International Journal of Molecular Sciences · 2 authors, 3 centres
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This narrative review integrates knowledge on intestinal transplant immunobiology and graft rejection mechanisms, highlighting the lack of reliable noninvasive biomarkers for monitoring rejection. It discusses allorecognition pathways, resident memory T cells, and potential biomarkers like citrulline and calprotectin, but notes that none are specific enough for clinical use.
Intestinal transplantation (ITx) is a lifesaving option for patients with irreversible intestinal failure, but it has a strong allogenic response leading to high rejection rates. The graft's immunogenicity is due to its lymphoid structures and exposure to microbiota. Methods: This is a narrative review that integrates basic immunological mechanisms and clinical biomarker research from experimental and human studies. Key Results: The review describes allorecognition pathways (direct, indirect, semi-direct, inverted direct) and the role of lymphoid structures in alloresponse. It highlights resident memory T cells (Trm) as key players in rejection. Biomarkers discussed include citrulline (sensitivity >80%, specificity 58%), fecal calprotectin (sensitivity 83%, specificity 77% at 92 mg/L), granzyme B and perforin (sensitivity 80% and 70%, specificity 87% for both), ST2 (sensitivity 62%, specificity 72.2%), and microbiome alterations (e.g., reduction in Firmicutes from 81% to 29% during rejection). Omics approaches have identified potential metabolites and proteins. Limitations: No noninvasive biomarkers are specific enough for diagnosis; issues with sensitivity, specificity, and confounding factors like immunosuppression and other conditions. Clinical studies are small and heterogeneous. Implications: Future research should explore two-way allogenicity, memory T cells, and advanced omics to develop better biomarkers for rejection monitoring.
