2017 - CIRTA

8- Immunological Monitoring, Rejection, and Mechanisms of Regeneration

36.7 - Significance of Donor HLA Antibodies in Small Bowel Transplantation

Presenter: Maria Paula, Villela Coelho, Sao Paulo, Brazil
Authors: Maria Paula Villela Coelho, David Briggs, Khalid Sharif, Paolo Muiesan, Sue Beath, Jane Hartley, Tamara Perera, Darius Mirza, Girish Gupte

Significance of Donor HLA Antibodies in Small Bowel Transplantation

Maria Paula Villela Coelho1, David Briggs2, Khalid Sharif1, Paolo Muiesan1, Sue V. Beath1, Jane L. Hartley1, Tamara Perera1, Darius Mirza1, Girish L. Gupte1.

1Liver Unit, Birmingham Children's Hospital NHS Trust, Birmingham, United Kingdom; 2Department of Histocompatibility and Immunogenetics, NHS Blood and Transplant, Birmingham Centre, Birmingham, United Kingdom

Introduction: Donor Specific Antibodies (DSA) is known to be an indicator of poor prognosis in most organ transplants but for small bowel transplant (SBTx) there is a paucity of studies. We have evaluated the outcomes of SBTx patients correlating the DSA samples collected with the occurrence of rejection episodes and graft failure.

Method: SBTx from April 1993 to October 2015 were reviewed, on all its modalities. The data comprise donor and recipient demographics, indications, DSA status, biopsies, immunosuppression, patient and graft survival. 318 DSA samples were collected from 51 patients over the period but not following a monitoring protocol. DSA samples were correlated with rejection episodes in SBTx and its impact on outcome. HLA antibodies were detected and measured in a single antigen bead assay.

Results: 94 SBTx were performed in 87 patients. Regarding to the type of transplant, 59.6% were Liver + SBTx, 31.9% Isolated SBTx, Multivisceral and Modified Multivisceral were 4.35% each. Sixty-nine patients had SB rejection at some point. 14 of these had at least one DSA positive sample.  In 16 no rejection cases tested for DSA one was positive, 2 patients had only liver rejection.  Despite the trend we do not see a significant association between DSA and rejection (Fisher’s p=0.24). Forty-one SBTx with acute rejection (AR) had HLA antibody tests undertaken and DSA was found in 10 cases (3 with antibodies against HLA class I, 4 against HLA DR, and 10 against HLA DQ). Graft loss was seen in 5/10 with DSA positive compared with 1/31 in the DSA negative cases (Fisher’s p=0.0018). In the 5 DSA positive graft loss cases, 4 of the antibodies are HLA DQ-specific and were persistent while in the remaining case the antibody was against donor HLA DR and this became undetectable before graft failure. There were 5 DSA (2 HLA Class I, 1 HLA DR, 5 HLA DQ) positive cases without graft loss to date and in all but one of these the antibodies were transient.

Conclusion: Rejection is not significantly associated with DSA in our analysis.  However, we have found a significant association of graft loss with DSA and this seems to relate to antibody persistence.   Antibodies against donor HLA DQ dominate this association and this is consistent with other forms of transplantation where these antibodies correlate with chronic rejection.  A protocol of routine DSA testing therefore seems warranted, particularly in patients having experienced AR.

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