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Prevalence and Clinical Impact of Donor-Specific Alloantibody Among Intestinal Transplant Recipients.
Transplantation. 2017 04; 101(4):873-882.T

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.

Authors+Show Affiliations

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.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

27490417

Citation

Cheng, Elaine Y., et al. "Prevalence and Clinical Impact of Donor-Specific Alloantibody Among Intestinal Transplant Recipients." Transplantation, vol. 101, no. 4, 2017, pp. 873-882.
Cheng EY, Everly MJ, Kaneku H, et al. Prevalence and Clinical Impact of Donor-Specific Alloantibody Among Intestinal Transplant Recipients. Transplantation. 2017;101(4):873-882.
Cheng, E. Y., Everly, M. J., Kaneku, H., Banuelos, N., Wozniak, L. J., Venick, R. S., Marcus, E. A., McDiarmid, S. V., Busuttil, R. W., Terasaki, P. I., & Farmer, D. G. (2017). Prevalence and Clinical Impact of Donor-Specific Alloantibody Among Intestinal Transplant Recipients. Transplantation, 101(4), 873-882. https://doi.org/10.1097/TP.0000000000001391
Cheng EY, et al. Prevalence and Clinical Impact of Donor-Specific Alloantibody Among Intestinal Transplant Recipients. Transplantation. 2017;101(4):873-882. PubMed PMID: 27490417.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Prevalence and Clinical Impact of Donor-Specific Alloantibody Among Intestinal Transplant Recipients. AU - Cheng,Elaine Y, AU - Everly,Matthew J, AU - Kaneku,Hugo, AU - Banuelos,Nubia, AU - Wozniak,Laura J, AU - Venick,Robert S, AU - Marcus,Elizabeth A, AU - McDiarmid,Suzanne V, AU - Busuttil,Ronald W, AU - Terasaki,Paul I, AU - Farmer,Douglas G, PY - 2016/8/5/pubmed PY - 2017/5/23/medline PY - 2016/8/5/entrez SP - 873 EP - 882 JF - Transplantation JO - Transplantation VL - 101 IS - 4 N2 - 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. SN - 1534-6080 UR - https://www.unboundmedicine.com/medline/citation/27490417/Prevalence_and_Clinical_Impact_of_Donor_Specific_Alloantibody_Among_Intestinal_Transplant_Recipients_ L2 - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&PAGE=linkout&SEARCH=27490417.ui DB - PRIME DP - Unbound Medicine ER -