Evaluation of c4d deposition and circulating antibody in small bowel transplantation

N Patey-Mariaud de Serre1, D Canioni, F Lacaille

  • 1Necker Enfants Malades-Pathology, Tumorothèque, Paris, France. natacha.patey-mariaud@nck.aphp.fr

Insights

Defining antibody-mediated rejection (AMR) in small bowel transplantation (SBTx) is challenging. Vascular lesions, not C4d deposition or donor-specific antibodies (DSA), appear to be a key indicator of acute rejection (AR) and poor outcomes in pediatric SBTx.

Area of Science:

  • Transplantation immunology
  • Gastroenterology
  • Pediatric surgery

Background:

  • Consensus criteria for antibody-mediated rejection (AMR) exist for kidney and heart transplants, involving histology, donor-specific antibodies (DSA), and C4d deposition.
  • Such criteria are not established for small bowel transplantation (SBTx), hindering accurate diagnosis and management of AMR in these patients.

Purpose of the Study:

  • To investigate the utility of established AMR criteria (histology, DSA, C4d) in pediatric small bowel transplantation (SBTx).
  • To identify reliable markers for acute rejection (AR) and predict outcomes in SBTx recipients.

Main Methods:

  • Retrospective analysis of 91 biopsies from 12 pediatric SBTx recipients (including retransplantation and combined liver-SBTx).
  • Evaluation of histological changes, vascular lesions, C4d deposition, and circulating donor-specific antibodies (DSA) in sera.
  • Standardized grading scheme for acute rejection (AR) and assessment of clinical outcomes.

Main Results:

  • C4d deposition was observed in 37% of biopsies and 50% with severe vascular lesions, but showed no clinical relevance to SBTx outcome.
  • Donor-specific antibodies (DSA) were not detected in any patient sera.
  • Severe vascular lesions were consistently associated with acute rejection (AR) and poor graft outcomes, with high mortality or graft loss for grades 2-3 AR within three months.

Conclusions:

  • C4d deposition and DSA are not reliable indicators of AMR in pediatric SBTx.
  • Grading of vascular lesions is a crucial marker for identifying acute rejection (AR) potentially resistant to standard treatment, guiding consideration for alternative therapies in SBTx.

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