{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:48:24Z","timestamp":1787028504256,"version":"build-2736575974"},"reference-count":113,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2023,2,25]],"date-time":"2023-02-25T00:00:00Z","timestamp":1677283200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Agencia I+D+I of the Argentinean government","award":["PICTA 2021 0060"],"award-info":[{"award-number":["PICTA 2021 0060"]}]},{"name":"Agencia I+D+I of the Argentinean government","award":["ALFGBG-965015"],"award-info":[{"award-number":["ALFGBG-965015"]}]},{"name":"Agencia I+D+I of the Argentinean government","award":["ALFGBG-872411"],"award-info":[{"award-number":["ALFGBG-872411"]}]},{"name":"Swedish government and the country councils","award":["PICTA 2021 0060"],"award-info":[{"award-number":["PICTA 2021 0060"]}]},{"name":"Swedish government and the country councils","award":["ALFGBG-965015"],"award-info":[{"award-number":["ALFGBG-965015"]}]},{"name":"Swedish government and the country councils","award":["ALFGBG-872411"],"award-info":[{"award-number":["ALFGBG-872411"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Intestinal transplantation (ITx) remains a lifesaving option for patients suffering from irreversible intestinal failure and complications from total parenteral nutrition. Since its inception, it became obvious that intestinal grafts are highly immunogenic, due to their high lymphoid load, the abundance in epithelial cells and constant exposure to external antigens and microbiota. This combination of factors and several redundant effector pathways makes ITx immunobiology unique. To this complex immunologic situation, which leads to the highest rate of rejection among solid organs (&gt;40%), there is added the lack of reliable non-invasive biomarkers, which would allow for frequent, convenient and reliable rejection surveillance. Numerous assays, of which several were previously used in inflammatory bowel disease, have been tested after ITx, but none have shown sufficient sensibility and\/or specificity to be used alone for diagnosing acute rejection. Herein, we review and integrate the mechanistic aspects of graft rejection with the current knowledge of ITx immunobiology and summarize the quest for a noninvasive biomarker of rejection.<\/jats:p>","DOI":"10.3390\/ijms24054541","type":"journal-article","created":{"date-parts":[[2023,2,27]],"date-time":"2023-02-27T03:23:36Z","timestamp":1677468216000},"page":"4541","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Intestinal Transplant Immunology and Intestinal Graft Rejection: From Basic Mechanisms to Potential Biomarkers"],"prefix":"10.3390","volume":"24","author":[{"given":"Martin","family":"Rumbo","sequence":"first","affiliation":[{"name":"Instituto de Estudios Inmunol\u00f3gicos y Fisiopatol\u00f3gicos, Facultad de Ciencias Exactas, Universidad Nacional de La Plata\u2014CONICET, Boulevard 120 y 62, La Plata 1900, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3783-5207","authenticated-orcid":false,"given":"Mihai","family":"Oltean","sequence":"additional","affiliation":[{"name":"The Transplant Institute, Sahlgrenska University Hospital, 413 45 Gothenburg, Sweden"},{"name":"Department of Surgery at Institute of Clinical Sciences, Sahlgrenska Academy at the University of Gothenburg, 413 90 Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1016\/j.gtc.2018.01.011","article-title":"Adult Intestinal Transplantation","volume":"47","author":"Matsumoto","year":"2018","journal-title":"Gastroenterol. Clin. N. Am."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1111\/ajt.12979","article-title":"Intestinal transplant registry report: Global activity and trends","volume":"15","author":"Grant","year":"2015","journal-title":"Am. J. Transplant."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1097\/00007890-199901150-00022","article-title":"The role of CD8 and CD4 T cells in intestinal allograft rejection: A comparison of monoclonal antibody-treated and knockout mice","volume":"67","author":"He","year":"1999","journal-title":"Transplantation"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"959","DOI":"10.1097\/00007890-199710150-00004","article-title":"Treatment with either anti-CD4 or anti-CD8 monoclonal antibodies blocks \u03b1\u03b2 T cell-mediated rejection of intestinal allografts in mice","volume":"64","author":"Newell","year":"1997","journal-title":"Transplantation"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1239","DOI":"10.1016\/S0041-1345(98)01978-2","article-title":"Differential effect of an anti-CD8 monoclonal antibody on rejection of murine intestine and cardiac allografts","volume":"31","author":"He","year":"1999","journal-title":"Transplant. Proc."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2358","DOI":"10.4049\/jimmunol.163.5.2358","article-title":"Cutting edge: Blockade of the CD28\/B7 costimulatory pathway inhibits intestinal allograft rejection mediated by CD4+ but not CD8+ T cells","volume":"163","author":"Newell","year":"1999","journal-title":"J. Immunol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1351","DOI":"10.1097\/00007890-200105150-00033","article-title":"CD8 T cell-mediated rejection of intestinal allografts is resistant to inhibition of the CD40\/CD154 costimulatory pathway","volume":"71","author":"Guo","year":"2001","journal-title":"Transplantation"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"4796","DOI":"10.4049\/jimmunol.167.9.4796","article-title":"Cutting Edge: Membrane Lymphotoxin Regulates CD8 + T Cell-Mediated Intestinal Allograft Rejection","volume":"167","author":"Guo","year":"2001","journal-title":"J. Immunol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1034\/j.1600-6143.2003.00088.x","article-title":"Role of 4-1BB in allograft rejection mediated by CD8+ T cells","volume":"3","author":"Wang","year":"2003","journal-title":"Am. J. Transplant."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/S0966-3274(02)00055-2","article-title":"Pathways of allorecognition: Implications for transplantation tolerance","volume":"10","author":"Game","year":"2002","journal-title":"Transpl. Immunol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1038\/nri3738","article-title":"Regional specialization within the intestinal immune system","volume":"14","author":"Mowat","year":"2014","journal-title":"Nat. Rev. Immunol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/j.immuni.2021.11.008","article-title":"Epithelial colonization by gut dendritic cells promotes their functional diversification","volume":"55","author":"Rivera","year":"2022","journal-title":"Immunity"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1038\/s41385-021-00448-w","article-title":"Dendritic cell functions in the inductive and effector sites of intestinal immunity","volume":"15","author":"Luciani","year":"2022","journal-title":"Mucosal Immunol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2548","DOI":"10.3389\/fimmu.2018.02548","article-title":"T cell Allorecognition Pathways in Solid Organ Transplantation","volume":"9","author":"Siu","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2643","DOI":"10.4049\/jimmunol.1102830","article-title":"Germinal center alloantibody responses are mediated exclusively by indirect-pathway CD4 T follicular helper cells","volume":"188","author":"Conlon","year":"2012","journal-title":"J. Immunol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"4828","DOI":"10.4049\/jimmunol.173.8.4828","article-title":"A novel pathway of alloantigen presentation by dendritic cells","volume":"173","author":"Herrera","year":"2004","journal-title":"J. Immunol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"12788","DOI":"10.1073\/pnas.1513533112","article-title":"CD8 T-cell recognition of acquired alloantigen promotes acute allograft rejection","volume":"112","author":"Harper","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1097\/MOT.0000000000000372","article-title":"Donor-derived exosomes: The trick behind the semidirect pathway of allorecognition","volume":"22","author":"Morelli","year":"2017","journal-title":"Curr. Opin. Organ Transplant."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1097\/MOT.0b013e3283534eb0","article-title":"How can pathologists help to diagnose late complications in small bowel and multivisceral transplantation?","volume":"17","author":"Ruiz","year":"2012","journal-title":"Curr. Opin. Organ Transplant."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1016\/j.transproceed.2016.10.025","article-title":"Successful Rescue of Late-onset Antibody-mediated Rejection 12 Years After Living-donor Intestinal Transplantation: A Case Report","volume":"49","author":"Wu","year":"2017","journal-title":"Transplant. Proc."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"3181","DOI":"10.1016\/j.transproceed.2019.08.012","article-title":"Severe Late-Onset Acute Cellular Rejection in a Pediatric Patient With Isolated Small Intestinal Transplant Rescued With Aggressive Immunosuppressive Approach: A Case Report","volume":"51","author":"Narang","year":"2019","journal-title":"Transplant. Proc."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2563","DOI":"10.1111\/j.1600-6143.2006.01516.x","article-title":"Donor lymphoid organs are a major site of alloreactive T-cell priming following intestinal transplantation","volume":"6","author":"Wang","year":"2006","journal-title":"Am. J. Transplant."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1111\/j.1365-2249.2010.04192.x","article-title":"Analysis of immune cells draining from the abdominal cavity as a novel tool to study intestinal transplant immunobiology","volume":"162","author":"Meier","year":"2010","journal-title":"Clin. Exp. Immunol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2148","DOI":"10.1111\/ajt.12797","article-title":"Immunological status of isolated lymphoid follicles after intestinal transplantation","volume":"14","author":"Meier","year":"2014","journal-title":"Am. J. Transplant."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1038\/s41385-021-00389-4","article-title":"Human gut-associated lymphoid tissues (GALT); diversity, structure, and function","volume":"14","author":"Fenton","year":"2021","journal-title":"Mucosal Immunol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1111\/j.1365-2249.2009.03883.x","article-title":"Comparative analysis of mononuclear cells isolated from mucosal lymphoid follicles of the human ileum and colon","volume":"156","author":"Junker","year":"2009","journal-title":"Clin. Exp. Immunol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"eabg1046","DOI":"10.1126\/scitranslmed.abg1046","article-title":"Inverted direct allorecognition triggers early donor-specific antibody responses after transplantation","volume":"14","author":"Charmetant","year":"2022","journal-title":"Sci. Transl. Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"eadd2145","DOI":"10.1126\/scitranslmed.add2145","article-title":"Passenger donor lymphocytes: To affinity and beyond","volume":"14","author":"Manook","year":"2022","journal-title":"Sci. Transl. Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1016\/S0198-8859(03)00113-7","article-title":"Four-color flow cytometric analysis of peripheral blood donor cell chimerism","volume":"64","author":"Metes","year":"2003","journal-title":"Hum. Immunol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"777756","DOI":"10.3389\/fimmu.2021.777756","article-title":"High Throughput Human T Cell Receptor Sequencing: A New Window Into Repertoire Establishment and Alloreactivity","volume":"12","author":"Fu","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"eaah3732","DOI":"10.1126\/sciimmunol.aah3732","article-title":"Bidirectional intragraft alloreactivity drives the repopulation of human intestinal allografts and correlates with clinical outcome","volume":"1","author":"Zuber","year":"2016","journal-title":"Sci. Immunol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1016\/j.humimm.2017.12.011","article-title":"Immune monitoring of transplant patients in transient mixed chimerism tolerance trials","volume":"79","author":"Sykes","year":"2018","journal-title":"Hum. Immunol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1639","DOI":"10.1097\/TP.0000000000001064","article-title":"A new window into the human alloresponse","volume":"100","author":"DeWolf","year":"2016","journal-title":"Transplantation"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1055\/s-0038-1632375","article-title":"Modified Multivisceral Transplantation with Native Spleen Removal in Rats","volume":"29","author":"Stringa","year":"2019","journal-title":"Eur. J. Pediatr. Surg."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1016\/j.stem.2018.11.007","article-title":"Human Intestinal Allografts Contain Functional Hematopoietic Stem and Progenitor Cells that Are Maintained by a Circulating Pool","volume":"24","author":"Fu","year":"2019","journal-title":"Cell Stem Cell"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"e141698","DOI":"10.1172\/JCI141698","article-title":"Lymphohematopoietic graft-versus-host responses promote mixed chimerism in patients receiving intestinal transplantation","volume":"131","author":"Fu","year":"2021","journal-title":"J. Clin. Investig."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1132","DOI":"10.1097\/TP.0000000000004000","article-title":"Emerging Concepts of Tissue-resident Memory T Cells in Transplantation","volume":"106","author":"Fu","year":"2022","journal-title":"Transplantation"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"eabc8122","DOI":"10.1126\/sciimmunol.abc8122","article-title":"Resident memory T cells form during persistent antigen exposure leading to allograft rejection","volume":"6","author":"Tieu","year":"2021","journal-title":"Sci. Immunol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"eabk0270","DOI":"10.1126\/sciadv.abk0270","article-title":"Skin and heart allograft rejection solely by long-lived alloreactive TRM cells in skin of severe combined immunodeficient mice","volume":"8","author":"Tian","year":"2022","journal-title":"Sci. Adv."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1238","DOI":"10.1111\/ajt.16283","article-title":"Rejection of intestinal allotransplants is driven by memory T helper type 17 immunity and responds to infliximab","volume":"21","author":"Kroemer","year":"2020","journal-title":"Am. J. Transplant."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1038\/s41385-020-0315-5","article-title":"CD4+ T cells persist for years in the human small intestine and display a TH1 cytokine profile","volume":"14","author":"Landsverk","year":"2021","journal-title":"Mucosal Immunol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2412","DOI":"10.1084\/jem.20190414","article-title":"Resident memory CD8 T cells persist for years in human small intestine","volume":"216","author":"Landsverk","year":"2019","journal-title":"J. Exp. Med."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1038\/276711a0","article-title":"Occurrence of Ia antigens on tissues of non-lymphoid origin","volume":"276","author":"Wiman","year":"1978","journal-title":"Nature"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1038\/293150a0","article-title":"Graft-versus-host disease induces expression of Ia antigen in rat epidermal cells and gut epithelium","volume":"293","author":"Mason","year":"1981","journal-title":"Nature"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1307","DOI":"10.1016\/j.cell.2018.10.008","article-title":"T Helper Cell Cytokines Modulate Intestinal Stem Cell Renewal and Differentiation","volume":"175","author":"Biton","year":"2018","journal-title":"Cell"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"109916","DOI":"10.1016\/j.celrep.2021.109916","article-title":"Epithelial-myeloid exchange of MHC class II constrains immunity and microbiota composition","volume":"37","author":"Stephens","year":"2021","journal-title":"Cell Rep."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"e46","DOI":"10.4110\/in.2022.22.e46","article-title":"Context-Dependent Regulation of Type17 Immunity by Microbiota at the Intestinal Barrier","volume":"22","author":"Akuzum","year":"2022","journal-title":"Immune Netw."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1038\/nature12240","article-title":"Innate lymphoid cells regulate CD4+ T-cell responses to intestinal commensal bacteria","volume":"498","author":"Hepworth","year":"2013","journal-title":"Nature"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"744","DOI":"10.1038\/s41586-022-05141-x","article-title":"ILC3s select microbiota-specific regulatory T cells to establish tolerance in the gut","volume":"610","author":"Lyu","year":"2022","journal-title":"Nature"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"101288","DOI":"10.1016\/j.trim.2020.101288","article-title":"Acute cellular rejection in small-bowel transplantation impairs NCR+ innate lymphoid cell subpopulation 3\/interleukin 22 axis","volume":"60","author":"Rumbo","year":"2020","journal-title":"Transpl. Immunol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1111\/ajt.16163","article-title":"Type 3 innate lymphoid cells are associated with a successful intestinal transplant","volume":"21","author":"Kang","year":"2021","journal-title":"Am. J. Transplant."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1111\/ajt.13435","article-title":"Innate Lymphoid Cells Groups 1 and 3 in the Epithelial Compartment of Functional Human Intestinal Allografts","volume":"16","author":"Talayero","year":"2016","journal-title":"Am. J. Transplant."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1729","DOI":"10.1097\/01.tp.0000188168.45003.63","article-title":"Utilization of dried blood spot citrulline level as a noninvasive method for monitoring graft function following intestinal transplantation","volume":"80","author":"Hee","year":"2005","journal-title":"Transplantation"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1124","DOI":"10.1111\/j.1600-6143.2004.00469.x","article-title":"An analysis of the association between serum citrulline and acute rejection among 26 recipients of intestinal transplant","volume":"4","author":"Pappas","year":"2004","journal-title":"Am. J. Transplant."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1039","DOI":"10.1111\/ctr.12630","article-title":"Plasma citrulline after small bowel transplantation: Effect of time from transplantation, acute cellular rejection, and renal failure","volume":"29","author":"Pironi","year":"2015","journal-title":"Clin. Transplant."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1111\/j.1600-6143.2004.00338.x","article-title":"Defining normal plasma citrulline in intestinal transplant recipients","volume":"4","author":"Gondolesi","year":"2004","journal-title":"Am. J. Transplant."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"2786","DOI":"10.1111\/j.1600-6143.2006.01513.x","article-title":"The value of plasma citrulline to predict mucosal injury in intestinal allografts","volume":"6","author":"Gondolesi","year":"2006","journal-title":"Am. J. Transplant."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1451","DOI":"10.1097\/00007890-199605270-00006","article-title":"Small bowel allograft rejection detected by serum intestinal fatty acid-binding protein is reversible","volume":"61","author":"Morrissey","year":"1996","journal-title":"Transplantation"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1058","DOI":"10.1097\/00007890-200104270-00008","article-title":"Lack of utility of intestinal fatty acid binding protein levels in predicting intestinal allograft rejection","volume":"71","author":"Kaufman","year":"2001","journal-title":"Transplantation"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1023\/A:1020505512364","article-title":"New insights into the fatty acid-binding protein (FABP) family in the small intestine","volume":"239","author":"Besnard","year":"2002","journal-title":"Mol. Cell. Biochem."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1111\/j.1432-2277.2003.tb00351.x","article-title":"Histamine-degrading enzymes as cellular markers of acute small bowel allograft rejection","volume":"16","author":"Klaus","year":"2003","journal-title":"Transpl. Int."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1002\/micr.10131","article-title":"Laser-Doppler flowmetry is reliable for early diagnosis of small-bowel acute rejection in the mouse","volume":"23","author":"Dindelegan","year":"2003","journal-title":"Microsurgery"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.jss.2003.12.028","article-title":"Increased apoptosis is specific for acute rejection in rat small bowel transplant","volume":"119","author":"Fishbein","year":"2004","journal-title":"J. Surg. Res."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1241","DOI":"10.1097\/01.TP.0000062840.49159.2F","article-title":"A schema for histologic grading of small intestine allograft acute rejection","volume":"75","author":"Wu","year":"2003","journal-title":"Transplantation"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1016\/j.transproceed.2004.01.079","article-title":"Histological criteria for the identification of acute cellular rejection in human small bowel allografts: Results of the pathology workshop at the VIII International Small Bowel Transplant Symposium","volume":"36","author":"Ruiz","year":"2004","journal-title":"Transplant. Proc."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"3061","DOI":"10.1016\/j.transproceed.2003.10.073","article-title":"Granzyme B and perforin as predictive markers for acute rejection in human intestinal transplantation","volume":"35","author":"Corti","year":"2003","journal-title":"Transplant. Proc."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1778","DOI":"10.1097\/TP.0b013e318177dfe4","article-title":"Blood monitoring of granzyme b and perforin expression after intestinal transplantation: Considerations on clinical relevance","volume":"85","author":"Altimari","year":"2008","journal-title":"Transplantation"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"8017","DOI":"10.1073\/pnas.0912678107","article-title":"Epithelial-derived IL-33 and its receptor ST2 are dysregulated in ulcerative colitis and in experimental Th1\/Th2 driven enteritis","volume":"107","author":"Pastorelli","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"938","DOI":"10.1111\/ajt.13542","article-title":"Elevated ST2 Distinguishes Incidences of Pediatric Heart and Small Bowel Transplant Rejection","volume":"16","author":"Mathews","year":"2016","journal-title":"Am. J. Transplant."},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Oltean, M., Bagge, J., Dindelegan, G., Kenny, D., Molinaro, A., Hellstr\u00f6m, M., Nilsson, O., Sihlbom, C., Casselbrant, A., and Davila, M. (2021). The Proteomic Signature of Intestinal Acute Rejection in the Mouse. Metabolites, 12.","DOI":"10.3390\/metabo12010023"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"690","DOI":"10.1097\/00007890-199409270-00009","article-title":"The correlation of intragraft cytokine expression with rejection in rat small intestine transplantation","volume":"58","author":"McDiarmid","year":"1994","journal-title":"Transplantation"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"989","DOI":"10.1097\/00007890-199511000-00019","article-title":"Differential expression of adhesion molecules during rat small bowel allograft rejection","volume":"60","author":"Reid","year":"1995","journal-title":"Transplantation"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1016\/j.transproceed.2003.12.022","article-title":"Intragraft heat shock protein-60 expression after small bowel transplantation in the mouse","volume":"36","author":"Oltean","year":"2004","journal-title":"Transplant. Proc."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/j.jss.2008.01.019","article-title":"Inducible nitric oxide synthase expression in the intestinal muscularis mediates severe smooth muscle dysfunction during acute rejection in allogenic rodent small bowel transplantation","volume":"150","author":"Schaefer","year":"2008","journal-title":"J. Surg. Res."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1038\/s41423-019-0216-2","article-title":"The innate immune response to allotransplants: Mechanisms and therapeutic potentials","volume":"16","author":"Ochando","year":"2019","journal-title":"Cell. Mol. Immunol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1038\/s41581-022-00600-0","article-title":"Activation and regulation of alloreactive T cell immunity in solid organ transplantation","volume":"18","author":"Duneton","year":"2022","journal-title":"Nat. Rev. Nephrol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1006\/jsre.1994.1121","article-title":"Intragraft expression of messenger RNA for interleukin-6 and tumor necrosis factor-alpha is a predictor of rat small intestine transplant rejection","volume":"57","author":"Farmer","year":"1994","journal-title":"J. Surg. Res."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1080\/00365520310000852","article-title":"Expression of mucosal addressin cell adhesion molecule-1 (MAdCAM-1) during small-bowel graft rejection in rats","volume":"38","author":"Fujisaki","year":"2003","journal-title":"Scand. J. Gastroenterol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1465","DOI":"10.1097\/TP.0b013e31816fc189","article-title":"Acute rejection and the muscularis propria after intestinal transplantation: The alloresponse, inflammation, and smooth muscle function","volume":"85","author":"Schaefer","year":"2008","journal-title":"Transplantation"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1283","DOI":"10.1016\/S0041-1345(00)01227-6","article-title":"Upregulated intragraft gene expression, ICAM-1 and IL-2R molecules, and apoptotic epithelial cells during rejection of rat small intestine allografts","volume":"32","author":"Li","year":"2000","journal-title":"Transplant. Proc."},{"key":"ref_81","first-page":"1417","article-title":"Circulating adhesion molecules and other soluble markers of immune activation in human small bowel and small bowel plus liver transplantation","volume":"26","author":"Satoh","year":"1994","journal-title":"Transplant. Proc."},{"key":"ref_82","first-page":"1152","article-title":"Serum levels of interleukin-6, tumor necrosis factor-alpha, and interleukin-2 in rejecting human small bowel allografts","volume":"24","author":"Noguchi","year":"1992","journal-title":"Transplant. Proc."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1111\/j.1365-2559.1993.tb00167.x","article-title":"In situ expression of cytokines and serine esterase B in small-bowel allograft rejection","volume":"22","author":"Peuchmaur","year":"1993","journal-title":"Histopathology"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"E137","DOI":"10.1111\/ctr.12078","article-title":"Serum albumin level during intestinal exfoliative rejection: A potential predictor of graft recovery and patient outcome","volume":"27","author":"Zambernardi","year":"2013","journal-title":"Clin. Transplant."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1111\/j.1432-2277.2011.01259.x","article-title":"Characteristic immune, apoptosis and inflammatory gene profiles associated with intestinal acute cellular rejection in formalin-fixed paraffin-embedded mucosal biopsies","volume":"24","author":"Asaoka","year":"2011","journal-title":"Transpl. Int."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1016\/j.trim.2011.07.005","article-title":"Effects of immunosuppressive therapy after experimental small bowel transplantation in rats","volume":"25","author":"Pech","year":"2011","journal-title":"Transpl. Immunol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1545","DOI":"10.1111\/j.1600-6143.2010.03117.x","article-title":"Influence of immunosuppression on alloresponse, inflammation and contractile function of graft after intestinal transplantation","volume":"10","author":"Fujishiro","year":"2010","journal-title":"Am. J. Transplant."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1365","DOI":"10.1111\/ctr.12464","article-title":"Immunosuppressive therapies after intestinal transplant modulate the expression of Th1 signature genes during acute cellular rejection. Implications in the search for rejection biomarkers","volume":"28","author":"Zambernardi","year":"2014","journal-title":"Clin. Transplant."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"e14378","DOI":"10.1111\/ctr.14378","article-title":"REG3\u03b1 is a novel biomarker that potentially correlates with acute allograft rejection after intestinal transplantation","volume":"35","author":"Smullin","year":"2021","journal-title":"Clin. Transplant."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1111\/j.1600-6143.2010.03383.x","article-title":"De novo donor HLA-specific antibodies after heart transplantation are an independent predictor of poor patient survival","volume":"11","author":"Smith","year":"2011","journal-title":"Am. J. Transplant."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"2193","DOI":"10.1681\/ASN.2020010019","article-title":"Eplet Mismatch Load and De Novo Occurrence of Donor-Specific Anti-HLA Antibodies, Rejection, and Graft Failure after Kidney Transplantation: An Observational Cohort Study","volume":"31","author":"Senev","year":"2020","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"3047","DOI":"10.1111\/j.1600-6143.2012.04237.x","article-title":"Preformed and de novo donor specific antibodies in visceral transplantation: Long-term outcome with special reference to the liver","volume":"12","author":"Wu","year":"2012","journal-title":"Am. J. Transplant."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1111\/tri.12250","article-title":"Clinical relevance of the de novo production of anti-HLA antibodies following intestinal and multivisceral transplantation","volume":"27","author":"Gerlach","year":"2014","journal-title":"Transpl. Int."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"e49","DOI":"10.1097\/TP.0000000000000614","article-title":"Prospective Monitoring of Donor-specific Anti-HLA Antibodies After Intestine\/Multivisceral Transplantation: Significance of De Novo Antibodies","volume":"99","author":"Kubal","year":"2015","journal-title":"Transplantation"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1097\/SLA.0b013e3180f61af4","article-title":"Calprotectin: A novel noninvasive marker for intestinal allograft monitoring","volume":"246","author":"Sudan","year":"2007","journal-title":"Ann. Surg."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"1281","DOI":"10.1097\/TP.0b013e31816dcea2","article-title":"Fecal calprotectin level measurements in small bowel allograft monitoring: A pilot study","volume":"85","author":"Akpinar","year":"2008","journal-title":"Transplantation"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.transproceed.2009.12.013","article-title":"Evaluation of Calprotectin Level in Intestinal Content as an Early Marker for Graft Rejection","volume":"42","author":"Cagnola","year":"2010","journal-title":"Transplant. Proc."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1080\/00365521.2017.1411523","article-title":"The endoscopic surveillance of the transplanted small intestine: A single center experience and a proposal for a grading score","volume":"53","author":"Varkey","year":"2018","journal-title":"Scand. J. Gastroenterol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1097\/TP.0b013e31821d262b","article-title":"Proteomic analysis reveals innate immune activity in intestinal transplant dysfunction","volume":"92","author":"Kumar","year":"2011","journal-title":"Transplantation"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1038\/s41467-017-02573-2","article-title":"Maturation of the gut microbiome and risk of asthma in childhood","volume":"9","author":"Stokholm","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"5881","DOI":"10.1038\/s41467-020-19589-w","article-title":"Imidazole propionate is increased in diabetes and associated with dietary patterns and altered microbial ecology","volume":"11","author":"Molinaro","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1159\/000516922","article-title":"The Comparison of fecal microbiota in left-side and right-side human colorectal cancer","volume":"62","author":"Miyake","year":"2021","journal-title":"Eur. Surg. Res."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"2683","DOI":"10.1016\/j.transproceed.2006.07.035","article-title":"Infectious complications after multivisceral transplantation in adults","volume":"38","author":"Oltean","year":"2006","journal-title":"Transplant. Proc."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/j.jss.2018.01.011","article-title":"Posttransplant complications in adult recipients of intestine grafts without bowel decontamination","volume":"225","author":"Clouse","year":"2018","journal-title":"J. Surg. Res."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1097\/00007691-199512000-00007","article-title":"Mode of action of tacrolimus (FK506): Molecular and cellular mechanisms","volume":"17","author":"Thomson","year":"1995","journal-title":"Ther. Drug. Monit."},{"key":"ref_106","doi-asserted-by":"crossref","unstructured":"Rivera, A., and Heitman, J. (2023). Natural product ligands of FKBP12: Immunosuppressive antifungal agents FK506, rapamycin, and beyond. PLoS Pathog., 19.","DOI":"10.1371\/journal.ppat.1011056"},{"key":"ref_107","doi-asserted-by":"crossref","unstructured":"Zaza, G., Dalla Gassa, A., Felis, G., Granata, S., Torriani, S., and Lupo, A. (2017). Impact of maintenance immunosuppressive therapy on the fecal microbiome of renal transplant recipients: Comparison between an everolimus- and a standard tacrolimus-based regimen. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0178228"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"17187","DOI":"10.1073\/pnas.0904847106","article-title":"Human gut microbiome adopts an alternative state following small bowel transplantation","volume":"106","author":"Hartman","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1111\/j.1600-6143.2011.03860.x","article-title":"Characterization of the ileal microbiota in rejecting and nonrejecting recipients of small bowel transplants","volume":"12","author":"Oh","year":"2012","journal-title":"Am. J. Transplant."},{"key":"ref_110","doi-asserted-by":"crossref","unstructured":"Girlanda, R., Liggett, J.R., Jayatilake, M., Kroemer, A., Guerra, J.F., Hawksworth, J.S., Radkani, P., Matsumoto, C.S., Zasloff, M., and Fishbein, T.M. (2022). The Microbiome and Metabolomic Profile of the Transplanted Intestine with Long-Term Function. Biomedicines, 10.","DOI":"10.3390\/biomedicines10092079"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"626","DOI":"10.1681\/ASN.2015010107","article-title":"Urine Metabolite Profiles Predictive of Human Kidney Allograft Status","volume":"27","author":"Suhre","year":"2016","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_112","doi-asserted-by":"crossref","unstructured":"Sigdel, T.K., Schroeder, A.W., Yang, J.Y.C., Sarwal, R.D., Liberto, J.M., and Sarwal, M.M. (2020). Targeted Urine Metabolomics for Monitoring Renal Allograft Injury and Immunosuppression in Pediatric Patients. J. Clin. Med., 9.","DOI":"10.3390\/jcm9082341"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"S18","DOI":"10.1111\/j.1600-6143.2012.04183.x","article-title":"Metabolomics of human intestinal transplant rejection","volume":"12","author":"Girlanda","year":"2012","journal-title":"Am. J. 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