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

Cheng, Elaine Y. MD; Everly, Matthew J. PharmD; Kaneku, Hugo MD; Banuelos, Nubia BS; Wozniak, Laura J. MD; Venick, Robert S. MD; Marcus, Elizabeth A. MD; McDiarmid, Suzanne V. MD; Busuttil, Ronald W. MD, PhD; Terasaki, Paul I. PhD; Farmer, Douglas G. MD

doi: 10.1097/TP.0000000000001391
Original Clinical Science-General

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.

As in other organ transplant recipients, the authors demonstrate in 109 intestine organ transplant recipients that pretransplant donor-specific antibodies (DSAs) and persistent de novo DSA are associated with a worse outcome than in patients without DSAs.

1 Department of Surgery, David Geffen School of Medicine at UCLA, Los Angeles, CA.

2 Terasaki Research Institute, Los Angeles, CA.

3 Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA.

4 Department of Pediatrics, David Geffen School of Medicine at UCLA, Los Angeles, CA.

Professor Paul Ichiro Terasaki passed away on January 25, 2016.

Received 10 February 2016. Revision received 17 May 2016.

Accepted 19 May 2016.

The authors declare no funding or conflicts of interest.

E.Y.C. participated in research design, performance of the research, data analysis, and writing of the article. M.J.E. participated in research design, performance of the research, data analysis, and writing of the article. H.K. participated in research design and performance of the research. N.B. participated in performance of the research. L.J.W. participated in research design and data analysis. R.S.V. participated in research design and data analysis. E.A.M. participated in research design and data analysis. S.V.M. participated in research design and data analysis. R.W.B. participated in research design and data analysis. D.G.F. participated in research design, performance of the research, data analysis, and writing of the article.

Correspondence: Elaine Y. Cheng, MD, 757 Westwood Plaza, Suite 8501, Los Angeles, CA 90095. (eycheng@mednet.ucla.edu).

Supplemental digital content (SDC) is available for this article. Direct URL citations appear in the printed text, and links to the digital files are provided in the HTML text of this article on the journal’s Web site (www.transplantjournal.com).

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