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Rejection is one of the most important drawbacks for graft and patient survival in intestinal and multivisceral transplantation. However, there is no consensus on the diagnostic criteria for humoral rejection, and the literature about the role of donor-specific antibodies (DSA) on allograft outcome and the risk factors that contribute to their development is scant with contradictory results. The present study analyzes the role of DSA exclusively in a pediatric cohort of 43 transplants. Among our patients, 11.6% showed preformed DSA, but they did not correlate with more rejection or less allograft survival. Having previous transplants was the main sensitization factor with an odds ratio (OR) = 44.85 (P = 0.001). In total, 16.3% of recipients developed de novo donor-specific antibodies (dnDSA), mostly directed against human leukocyte antigen (HLA) class II, polyspecific and complement fixing. Additionally, the presence of dnDSA had a deleterious effect on graft rejection (hazard ratio [HR] = 11.00; P = 0.01) and survival (HR = 66.52; P < 0.001) in an observational period of 5 years after transplantation. The inclusion of the liver emerged as the main protective factor against dnDSA development with an OR = 0.07 (P = 0.007). The analysis of HLA compatibility at the serological and epitope level with the computational tools HLAMatchmaker and PIRCHE revealed no association between HLA mismatching and dnDSA. In conclusion, this study performed in pediatric recipients shows the deleterious effect of dnDSA on intestinal transplantation supported by the complement-fixing activity observed. Additionally, the liver inclusion in the allografts showed to be a protective factor against dnDSA generation., (Copyright © 2018 by the American Association for the Study of Liver Diseases.)

In intestinal allografts, endoscopy and histology detect the injury once changes in the bowel wall architecture have occurred. We aimed to identify a molecular signature that could predict early deterioration, within histologically indistinguishable biopsies with "minimal changes" (MC) pathology. Sixty biopsies from 12 adult recipients were longitudinally taken during 8years post-transplant. They were classified as either stable (STA) or non-stable (NSTA) according to the prospectively recorded number, frequency and severity of rejection events of the allograft. In a discovery set of MC samples analyzed by RNA-Seq, 816 genes were differentially expressed in STA vs NSTA biopsies. A group of 5 genes (ADH1C, SLC39A4, CYP4F2, OPTN and PDZK1) correctly classified all NSTA biopsies in the discovery set and all STA biopsies from an independent set. These results were validated by qPCR in a new group of MC biopsies. Based on a logistic regression model, a cutoff of 0.28 predicted the probability of being a NSTA biopsy with 85% sensitivity and 69% specificity. In conclusion, by analyzing MC samples early after transplantation, the expression of a 5-gene set may predict the evolution of the bowel allograft. This prognostic biomarker may be of help to personalize care of the intestinal transplant recipient., (Copyright © 2017. Published by Elsevier Inc.)

Summary: To review our experience using sirolimus in a single centre paediatric intestinal transplantation cohort. Intestinal transplant patients with more than 3 months follow‐up were divided into two groups according to their immunosuppression regimen: tacrolimus, (TAC group, n = 45 grafts) or sirolimus (SRL group, n = 38 grafts), which included those partially or completely converted from tacrolimus to sirolimus. The indications to switch were tacrolimus side effects and immunological complications. Survival and complications were retrospectively analysed comparing both groups. SRL was introduced 9 months (0 months–16.9 years) after transplant. The main cause for conversion was worsening renal function (45%), followed by haemolytic anaemia (21%) and graft‐versus‐host‐disease (16%). Both groups showed a similar overall patient/graft survival (P = 0.76/0.08) and occurrence of rejection (24%/17%, P = 0.36). Immunological complications did not recur after conversion. Renal function significantly improved in most SRL patients. After a median follow‐up of 65.17 months, 28/46 survivors were on SRL, 26 with monotherapy, with good graft function. Over one‐third of our patients eventually required SRL conversion that allowed to improve their kidney function and immunological events, without entailing additional complications or survival impairment. Further trials are warranted to clarify the potential improvement of the standard tacrolimus maintenance by sirolimus conversion or addition. [ABSTRACT FROM AUTHOR]

Background: Mesenchymal stromal cells (MSC) have been proposed as a promising complement to standard immunosuppression in solid organ transplantation because of their immunomodulatory properties. The present work addresses the role of adipose‐derived MSC (Ad‐MSC) in an experimental model of acute rejection in small bowel transplantation (SBT). Material/Methods: Heterotopic allogeneic SBT was performed. A single dose of 1.5x106 Ad‐MSC was intra‐arterially delivered just before graft reperfusion. Animals were divided into CONTROL (CTRL), CONTROL+Ad‐MSC (CTRL_MSC), tacrolimus (TAC), and TAC+Ad‐MSC (TAC_MSC) groups. Each Ad‐MSC groups was subdivided in autologous and allogeneic third‐party groups. Results: Rejection rate and severity were similar in MSC‐treated and untreated animals. CTRL_MSC animals showed a decrease in macrophages, T‐cell (CD4, CD8, and Foxp3 subsets) and B‐cell counts in the graft compared with CTRL, this decrease was attenuated in TAC_MSC animals. Pro‐ and anti‐inflammatory cytokines and some chemokines and growth factors increased in CTRL_MSC animals, especially in the allogeneic group, whereas milder changes were seen in the TAC groups. Conclusion: Ad‐MSC did not prevent rejection when administered just before reperfusion. However, they showed immunomodulatory effects that could be relevant for a longer‐term outcome. Interference between tacrolimus and the MSC effects should be addressed in further studies. [ABSTRACT FROM AUTHOR]