Updates on acute and chronic rejection in small bowel and multivisceral allografts

Ruiz, Phillip

doi:10.1097/mot.0000000000000075

Cited by 35 publications

(17 citation statements)

References 52 publications

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“…With no reliable noninvasive markers, rejection has always been the most feared complication after ITX, and clinical symptoms like diarrhea, abdominal distension and febrile temperature were often seen and treated preemptively as surrogate markers of rejection . Histology of mucosal specimen remains the gold standard for detecting rejection , but it also yields the risk of graft ulceration or perforation and diagnostic pitfalls. In contrast, the skin component of the transplanted AW is easily accessible and can be monitored more consistently and less harmfully than visceral organs during the rejection process.…”

Section: Discussionmentioning

confidence: 99%

Abdominal Wall Transplantation: Skin as a Sentinel Marker for Rejection

Gerlach

Vrakas

Sawitzki

et al. 2016

American Journal of Transplantation

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These authors contributed equally.Abdominal wall transplantation (AWTX) has revolutionized difficult abdominal closure after intestinal transplantation (ITX). More important, the skin of the transplanted abdominal wall (AW) may serve as an immunological tool for differential diagnosis of bowel dysfunction after transplant. Between August 2008 and October 2014, 29 small bowel transplantations were performed in 28 patients (16 male, 12 female; aged 41 AE 13 years). Two groups were identified: the solid organ transplant (SOT) group (n = 15; 12 ITX and 3 modified multivisceral transplantation [MMVTX]) and the SOT-AWTX group (n = 14; 12 ITX and 2 MMVTX), with the latter including one ITX-AWTX retransplantation. Two doses of alemtuzumab were used for induction (30 mg, 6 and 24 h after reperfusion), and tacrolimus (trough levels 8-12 ng/mL) was used for maintenance immunosuppression. Patient survival was similar in both groups (67% vs. 61%); however, the SOT-AWTX group showed faster posttransplant recovery, better intestinal graft survival (79% vs. 60%), a lower intestinal rejection rate (7% vs. 27%) and a lower rate of misdiagnoses in which viral infection was mistaken and treated as rejection (14% vs. 33%). The skin component of the AW may serve as an immune modulator and sentinel marker for immunological activity in the host. This can be a vital tool for timely prevention of intestinal graft rejection and, more important, avoidance of overimmunosuppression in cases of bowel dysfunction not related to graft rejection.

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Section: Discussionmentioning

confidence: 99%

Abdominal Wall Transplantation: Skin as a Sentinel Marker for Rejection

Gerlach

Vrakas

Sawitzki

et al. 2016

American Journal of Transplantation

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“…Fundamentally, the adaptive immune response, principally comprised of recipient-derived T-cell and B-cell subpopulations, has a complex interplay with innate immune populations including NK cells, dendritic cells, innate lymphoid cells, and macrophages [49]. Our study assessed several crucial aspects involving NK cell activity, T-cell subpopulations, and related cytokines to determine the effect of Ad/HO-1/BMMSCs on acute rejection.…”

Section: Discussionmentioning

confidence: 99%

Heme oxygenase-1-transduced bone marrow mesenchymal stem cells in reducing acute rejection and improving small bowel transplantation outcomes in rats

et al. 2016

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BackgroundWe determined whether bone marrow mesenchymal stem cells (BMMSCs) transduced with heme oxygenase-1 (HO-1), a cytoprotective and immune-protective factor, could improve outcomes for small bowel transplantation (SBTx) in rats.MethodsWe performed heterotopic SBTx from Brown Norway rats to Lewis rats, before infusing Ad/HO-1-transduced BMMSCs (Ad/HO-1/BMMSCs) through the superficial dorsal veins of the penis. Respective infusions with Ad/BMMSCs, BMMSCs, and normal saline served as controls. The animals were sacrificed after 1, 5, 7, or 10 days. At each time point, we measured small bowel histology and apoptosis, HO-1 protein and mRNA expression, natural killer (NK) cell activity, cytokine concentrations in serum and intestinal graft, and levels of regulatory T (Treg) cells.ResultsThe saline-treated control group showed aggravated acute cellular rejection over time, with mucosal destruction, increased apoptosis, NK cell activation, and upregulation of proinflammatory and immune-related mediators. Both the Ad/BMMSC-treated group and the BMMSC-treated group exhibited attenuated acute cellular rejection at an early stage, but the effects receded 7 days after transplantation. Strikingly, the Ad/HO-1/BMMSC-treated group demonstrated significantly attenuated acute cellular rejection, reduced apoptosis and NK cell activity, and suppressed concentrations of inflammation and immune-related cytokines, and upregulated expression of anti-inflammatory cytokine mediators and increased Treg cell levels.ConclusionOur data suggest that Ad/HO-1-transduced BMMSCs have a reinforced effect on reducing acute rejection and protecting the outcome of SBTx in rats.

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“…62,136,137 The full thickness specimen showed histologic features pathognomonic of chronic rejection with severe obliterative arteriopathy, mesenteric sclerosis, and mesenteric lymph node depletion, with no evidence of granulomatous disease. 138,139 At the same time, another CD patient developed acute gastrointestinal symptoms 6 months after transplantation and the diagnosis of CD recurrence was suspected based upon clinical, endoscopic, and histopathologic findings. A few days later, the patient developed irreversible exfoliative rejection that required allograft enterectomy with no evidence of CD recurrence in the removed allograft.…”

Section: Disease Recurrencementioning

confidence: 99%

Management of Crohnʼs Disease in the New Era of Gut Rehabilitation and Intestinal Transplantation

Nyabanga

Kochhar

Costa

et al. 2016

Inflammatory Bowel Diseases

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Despite recent therapeutic advances, patients with Crohn's disease (CD) continue to experience high recurrence with cumulative structural damage and ultimate loss of nutritional autonomy. With short bowel syndrome, strictures, and enteric fistulae being the underlying pathology, CD is the second common indication for home parenteral nutrition (HPN). With development of intestinal failure, nutritional management including HPN is required as a rescue therapy. Unfortunately, some patients do not escape the HPN-associated complications. Therefore, the concept of gut rehabilitation has evolved as part of the algorithmic management of these patients, with transplantation being the ultimate life-saving therapy. With type 2 intestinal failure, comprehensive rehabilitative measures including nutritional care, pharmacologic manipulation, autologous reconstruction, and bowel lengthening is often successful, particularly in patients with quiescent disease. With type 3 intestinal failure, transplantation is the only life-saving treatment for patients with HPN failure and intractable disease. With CD being the second common indication for transplantation in adults, survival outcome continues to improve because of surgical innovation, novel immunosuppression, and better postoperative care. Despite being a rescue therapy, the procedure has achieved survival rates similar to other solid organs, and comparable to those who continue to receive HPN therapy. With similar technical, immunologic, and infectious complications, survival is similar in the CD and non-CD recipients. Full nutritional autonomy is achievable in most survivors with better quality of life and long-term cost-effectiveness. CD recurrence is rare with no impact on graft function. Further progress is anticipated with new insights into the pathogenesis of CD and mechanisms of transplant tolerance.

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Updates on acute and chronic rejection in small bowel and multivisceral allografts

Cited by 35 publications

References 52 publications

Abdominal Wall Transplantation: Skin as a Sentinel Marker for Rejection

Abdominal Wall Transplantation: Skin as a Sentinel Marker for Rejection

Heme oxygenase-1-transduced bone marrow mesenchymal stem cells in reducing acute rejection and improving small bowel transplantation outcomes in rats

Management of Crohnʼs Disease in the New Era of Gut Rehabilitation and Intestinal Transplantation

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