Infections in Intestinal and Multivisceral Transplantation

Girlanda, Raffaele; TimponeJr., Joseph G.; Soriano, Kevin; Fishbein, Thomas M.

doi:10.1007/978-1-4939-9034-4_5

Cited by 5 publications

(5 citation statements)

References 147 publications

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“…Namely, the propensity of donor lymphocytes transferred with the gut‐associated lymphoid tissue to cause graft‐versus‐host disease (GvHD), and the high early risk of post‐transplant lymphoproliferative disease (PTLD) with acquired Epstein–Barr virus (Berger et al., 2012; Santarsieri et al., 2022). Bacterial flora transferred with the graft also exposes patients to a greater infection risk when heavily immunosuppressed (Girlanda et al., 2019).…”

Section: Introductionmentioning

confidence: 99%

Exploring the immunological relevance of pre‐transplant donor‐specific antibody in intestinal transplantation, with special consideration to the liver

McArdle,

Cope,

Chaudhry

et al. 2024

Int J Immunogenetics

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Despite recent advances that have improved outcomes following intestinal transplantation (ITx), achieving long‐term patient survival and rejection‐free survival is still challenging. Understanding the relevance of pre‐transplant human leukocyte antigen (HLA) donor‐specific antibody (DSA) in ITx and the immunomodulatory potential of the liver within the allograft is crucial to providing an accurate assessment of pre‐transplant immunological risk, which could influence and improve post‐transplant outcomes further. This was the primary objective of this retrospective study of 95 adult ITx transplants which took place at Cambridge University Hospitals (United Kingdom) between 2007 and 2019. Two novel programs were developed and validated to identify DSA (tested by Luminex single antigen beads) in this dataset. Data analysis utilised Kaplan–Meier survival methods, and statistical analysis was performed using log‐rank tests and adjusted Cox models. Fifty‐four (57%) ITx cases contained a liver, and 36 (38%) were sensitised to HLA. Pre‐transplant DSA > 500 mean fluorescent intensity appeared to negatively affect post‐ITx patient survival and rejection outcomes. Additionally, liver‐inclusive allografts seemed to show particular resistance to HLA class I DSA. Our data hints towards consistency with other ITx studies where deleterious effects of DSA have been demonstrated, and where liver inclusion is protective from HLA class I DSA. This is in line with current national guidelines for immunological risk. Our publicly available research programs could support future large or multicentre studies where statistically relevant data might be gained.

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Section: Introductionmentioning

confidence: 99%

Exploring the immunological relevance of pre‐transplant donor‐specific antibody in intestinal transplantation, with special consideration to the liver

McArdle,

Cope,

Chaudhry

et al. 2024

Int J Immunogenetics

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“…Despite lymphodepleting induction therapy, high rejection rates limit transplant success and graft survival remains about 50% after 5 years 16 . Infection 17 , post-transplant lymphoproliferative disease 18 and graft-versus-host disease (GVHD) 19,20 also cause significant morbidity and mortality. At the time of transplant, lymphodepleting therapy reduces the recipient lymphoid mass while donor lymphocytes are transferred via the allograft at variable levels among isolated intestinal transplantation (iITx), liver-intestinal transplantation (LITx), and multivisceral transplantation (MVTx).…”

Section: Introductionmentioning

confidence: 99%

Dynamic establishment and maintenance of the human intestinal B cell population and repertoire following transplantation

Fu,

Hsiao,

Waffarn

et al. 2023

Preprint

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It is unknown how intestinal B cell populations and B cell receptor (BCR) repertoires are established and maintained over time in humans. Following intestinal transplantation (ITx), surveillance ileal mucosal biopsies provide a unique opportunity to map the dynamic establishment of gut lymphocyte populations. Using polychromatic flow cytometry that includes HLA allele group-specific mAbs distinguishing donor from recipient cells along with high throughput BCR sequencing, we tracked the establishment of recipient B cell populations and BCR repertoire in the allograft mucosa of ITx recipients. We confirm the early presence of naïve donor B cells in the circulation and, for the first time, document the establishment of recipient B cell populations, including B resident memory cells, in the intestinal allograft mucosa. Recipient B cell repopulation of the allograft was most rapid in infant (<1 year old)-derived allografts and, unlike T cell repopulation, did not correlate with rejection rates. While recipient memory B cell populations were increased in graft mucosa compared to circulation, naïve recipient B cells remained detectable in the graft mucosa for years. Comparisons of peripheral and intra-mucosal B cell repertoires in the absence of rejection revealed increased BCR mutation rates and clonal expansion in graft mucosa compared to circulating B cells, but these parameters did not increase markedly after the first year post-transplant. Furthermore, clonal mixing between the allograft mucosa and the circulation was significantly greater in ITx recipients, even years after transplantation, than in healthy control adults. Collectively, our data demonstrate intestinal mucosal B cell repertoire establishment from a circulating pool, a process that continues for years without evidence of establishment of a stable mucosal B cell repertoire.

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“…Infectious complications are common after intestinal and multivisceral transplantation, representing a relevant cause of morbidity and mortality among recipients, with reports indicating a risk of up to 90% for bacterial infections [ 6 ], 15–30% for cytomegalovirus infections and 30–50% for mycoses, respectively [ 7 ]. Of all bacterial infections observed in the early postoperative period, 60% evolve into bloodstream infections [ 8 ]. Solid organ transplant recipients are at high risk for infections caused by multidrug-resistant organisms (MDROs) [ 9 ] associated with a high attack rate and mortality, with studies reporting rates of up to 52% and 41%, respectively [ 10 ].…”

Section: Introductionmentioning

confidence: 99%

“…The translocation of microorganisms from the lumen of an intestinal allograft to sterile sites in the recipient is a plausible pathophysiological mechanism of postoperative infection [ 8 ]. However, according to current definitions adopted in Europe and the United States, donor-derived infections are considered proven or certain when clear laboratory evidence of the presence of the same infectious agent in the donor and the recipient is available.…”

Section: Introductionmentioning

confidence: 99%

Donor-derived vancomycin-resistant enterococci transmission and bloodstream infection after intestinal transplantation

Correa-Martínez

Becker

Schwierzeck

et al. 2020

Antimicrob Resist Infect Control

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Background Transplant recipients are at high risk for infections. However, donor-recipient transmission of multidrug-resistant organisms (MDROs) remains mostly unaddressed in the protocols of pre-transplant infection and colonization screening. Vancomycin-resistant enterococci (VRE) are MDROs that colonize the gastrointestinal tract and are associated with a significant burden of disease. Besides the high mortality of invasive VRE infections, chronic colonization leads to costly isolation measures in the hospital setting. Whereas most post-transplantation VRE infections are endogenous and thus preceded by colonization of the recipient, conclusive evidence of VRE transmission via allograft in the context of intestinal transplantation is lacking. Case presentation We describe a donor-derived VRE infection after intestinal transplantation including small bowel and right hemicolon. The recipient, a 54-year old male with history of mesenteric ischemia and small bowel perforation due to generalized atherosclerosis and chronic stenosis of the celiac trunk and the superior mesenteric artery, developed an intra-abdominal infection and bloodstream infection after transplantation. VRE isolates recovered from the patient as well as from the allograft prior to transplantation were analyzed via whole genome sequencing. Isolates showed to be genetically identical, thus confirming the transmission from donor to recipient. Conclusions This case underlines the relevance of donor-recipient VRE transmission and invasive infection in the context of intestinal transplantation, highlighting the need for preoperative MDRO screening that facilitates the prompt and effective treatment of possible infections as well as the timely establishment of contact precautions to prevent further spread.

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Infections in Intestinal and Multivisceral Transplantation

Cited by 5 publications

References 147 publications

Exploring the immunological relevance of pre‐transplant donor‐specific antibody in intestinal transplantation, with special consideration to the liver

Exploring the immunological relevance of pre‐transplant donor‐specific antibody in intestinal transplantation, with special consideration to the liver

Dynamic establishment and maintenance of the human intestinal B cell population and repertoire following transplantation

Donor-derived vancomycin-resistant enterococci transmission and bloodstream infection after intestinal transplantation

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