Mucosal Vascular Alterations in Isolated Small‐Bowel Allografts: Relationship to Humoral Sensitization

Abstract

Acute vascular rejection (AVR) in human small-bowel transplantation is an inadequately characterized entity whose frequency and severity is not well understood. As compared to severe AVR, changes identifying early, mild or evolving AVR are not known. We created a scoring system to evaluate subtle mucosal vascular changes and examined 188 biopsies from 21 patients obtained in the first 3 months post transplant. A majority of patients had a transient rise in vascular injury, often within 30 days of transplant. Small-vessel congestion and erythrocyte extravasation were the most common alterations. The vascular injury score was not related to acute cellular rejection, HLA type or HLA antigen disparities. However, the patients with the vascular changes had significantly higher peak panel reactive antibodies (PRA) and a higher incidence of positive T-cell and B-cell crossmatch. Finally, graft survival was significantly lower in the patients demonstrating the early vascular lesions. These data suggest that the vascular injury is partially associated with humoral presensitization of the recipient and may be a form of acute vascular rejection. Since these vascular changes are frequent, we advocate early post-transplant monitoring to identify and manage potentially high-risk patients.

Evaluation of C4d Deposition and Circulating Antibody in Small Bowel Transplantation

“…During one study using C4d staining, the authors concluded there was a limited relevance of C4d (16). Another study suggested that vascular injury is partially associated with humoral presensitization and could be a form of acute vascular rejection (11). In a third study, the development of DSA was shown to be significantly associated with acute rejection (AR) episodes (10).…”

“…The surrounding interstitium was assessed for the presence of extravasated erythrocytes and edema (11).…”

“…As the lesions due to AMR in the kidney differ from those described in cellular rejection, we have hypothesized that humoral rejection after SBTx could appear as a specific, but not yet recognized, histological pattern associated with a characteristic C4d mucosal capillary deposition or vascular alterations (4,10,11).…”

“…T-cell-mediated rejection is morphologically well defined in all transplanted organs. The lesions caused by antibody-mediated rejection (AMR) are well recognized and have been characterized in some organs such as kidney and heart allograft, but they have not been described in the context of small bowel allografts (5)(6)(7)(8)(9)(10)(11).…”

“…Only a small number of publications have focused on AMR in intestinal allograft recipients (10,11,16). During one study using C4d staining, the authors concluded there was a limited relevance of C4d (16).…”