Prevalence and Clinical Impact of Donor-Specific Alloantibody Among Intestinal Transplant Recipients

Abstract

Background: Rejection remains the leading cause of allograft loss, and a major barrier to improving long-term outcomes after intestinal transplantation. Our aim is to define the prevalence and investigate the role of donor-specific antibody (DSA) on intestinal graft outcomes.

Methods: The study includes 109 transplants performed in 95 recipients at a single center. Patients were screened for DSA pretransplant, monitored regularly posttransplant and when clinically indicated using the single-antigen bead Luminex assay. Standard induction immunosuppression was with interleukin-2 receptor antagonists, and antithymocyte globulin in high-risk recipients. Maintenance regimens were tacrolimus-based.

Results: Pretransplant DSA was detected in 12 (11%) recipients with 50% continuing to have circulating antibodies posttransplant. An additional 24 (25%) patients developed de novo DSA, and of these, 71% had persistent antibodies. Recipients with preformed DSA demonstrated elevated risks of early graft failure, whereas those with de novo DSA experienced accelerated graft loss once DSA was detected, reaching a 28% failure rate within 2 years. HLA-DQ mismatch is a significant risk factor for de novo DSA emergence, whereas the persistence of antibodies is predicted by DSA strength and specificity. Although inclusion of the liver in the intestinal allograft imparts an immunological advantage against rejection-related graft loss, this protective effect was lost among recipients with persistent DSA.

Conclusions: The presence of DSA is associated with inferior graft outcomes among intestinal transplant recipients. An enhanced understanding of the mechanisms by which DSA causes allograft injury, and effective strategies targeting humoral immune reactivity are needed to improve long-term intestinal graft outcomes.

FIGURE 1.

Schema of the entire study population according to DSA status. The study includes 109 transplants performed in 95 recipients.

FIGURE 2.

Incidence of de novo DSA development according to the degree of DQ mismatch (DQ-MM). A 2-antigen MM at the HLA-DQ locus is associated with de novo DSA emergence (P = 0.008 vs 0-antigen mismatch and 1-antigen mismatch).

FIGURE 3.

Percentage of class I vs. class II DSA in relation to DSA persistence. A, Preformed DSA show a high proportion of class I antibodies which are preferentially cleared posttransplant. B, De novo DSA are commonly directed against class II antigens and likely to persist.

FIGURE 4.

Cumulative incidence of acute rejection by A, type of DSA and B, persistent DSA.

FIGURE 5.

Death-censored graft survival A, from the time of transplantation stratified by DSA type. Preformed DSA was associated with early allograft failure due to rejection. There were no significant differences in graft survival between recipients with no DSA and those with de novo DSA. B, Accelerated graft loss was observed from the time of de novo DSA detection, with a 10% failure rate at 1-year and 28% at 2-years. C, Persistent DSA is associated with inferior posttransplant graft survival. D, Subgroup analysis of 22 recipients who underwent protocol monitoring of DSA in the early posttransplant period, showing that persistent DSA is associated with an increased risk of accelerated graft failure.

FIGURE 6.

Allograft survival in relation to inclusion of the liver and DSA persistence.