2017 - CIRTA


1- Rejection of the Intestine Allograft

15.5 - Refinement of histological criteria of acute humoral rejection in small bowel transplantation

Presenter: Marion, Rabant, PARIS, France
Authors: Marion Rabant, Maud Racapé, Olivier Aubert, Laetitia-Marie Petit, Julie Bruneau, Patrick Barbet, Olivier Goulet, Christophe Chardot, Jean Luc Taupin, Florence Lacaille, Danielle Canioni, Jean-Paul Duong Van Huyen


Refinement of histological criteria of acute humoral rejection in small bowel transplantation

Marion Rabant1, Maud Racapé2, Olivier Aubert2, Laetitia-Marie Petit3, Julie Bruneau1, Patrick Barbet1, Olivier Goulet3, Christophe Chardot4, Jean Luc Taupin5, Florence Lacaille3, Danielle Canioni1, Jean-Paul Duong Van Huyen1.

1Pathology, Necker-Enfants malades Hospital, Paris, France; 2PARCC Research unit, European George Pompidou Hospital, Paris, France; 3Pediatric hepatogastroenterology, Necker-Enfants malades Hospital, Paris, France; 4Surgery, Necker-Enfants malades Hospital, Paris, France; 5Histocompatibility laboratory, Saint-Louis Hospital, Paris, France

Background: Diagnosis criteria of acute humoral rejection in small bowel transplantation (SBT) are not clearly defined, although the presence of preformed or de novo DSA has been reported to be deleterious for SBT survival.

Methods: We retrospectively studied all intestinal biopsies obtained in the first year of transplantation from our cohort of SBT patients (n=23) between May, 2009 and November, 2014. We systematically looked for C4d staining, semi-quantitatively assessed according to the Banff 2007 classification, and for signs of cellular rejection (apoptosis), vascular lesions (capillaritis, thrombosis, hemorrage congestion), oedema of the chorion, lamina propria inflammation and mucous ulcerations. Identification of anti-HLA DSAs and their ability to fix C1q was performed by Luminex Single Antigen.

Results: We assessed 345 biopsies (17±6 biopsies per patient) from these 23 patients. Among these patients, 3 did not develop DSAs. From the remaining 20 DSA+ patients, 7 (35%) had a C1q-binding DSA. 78 biopsies (22.6%) were C4d+ (grade≥2). Multivariate logistic regression analysis revealed that 3 histological parameters were independently and significatively associated with the presence of C4d on the biopsy: capillaritis (OR 2.883, p=0.003), mucosal ulceration (OR 3.429, p=0.003) and presence of apoptosis (OR 1.957, p=0.036). Patients with less than 15% of C4d+ biopsies had a better graft survival (86% at 2 years) compared to patients with 15 to 30% of C4d+ biopsies (53% at 2 years) and to patients with more than 30% of C4d+ biopsies (18% at 2 years, log-rank test p=0.0015).

Conclusion: The presence of C4d positive biopsies (grade≥2) in the first year of SBT is significantly associated with capillaritis, ulceration and apoptosis, as well as a worse graft survival at 2 years. These histological signs are relevant for acute humoral rejection diagnosis in SBT.


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