Rises and Falls in Donor-Specific and Third-Party HLA Antibody Levels After Antibody Incompatible Transplantation

Higgins, Rob; Lowe, David; Hathaway, Mark; Lam, F. T.; Kashi, Habib; Tan, Liang; Imray, C.; Fletcher, Simon; Chen, Klaus; Krishnan, Nithya; Hamer, Rizwan; Zehnder, Daniel; Briggs, David

doi:10.1097/tp.0b013e31819a6788

Cited by 36 publications

(33 citation statements)

References 18 publications

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“…The class of HLA specificity was not significant, in other words, combinations of DSA including those to HLA DP and DQ as well as to HLA DR were associated with increased risk, especially in combination with HLA class I DSA, as previously suggested. 28 …”

Section: Discussionmentioning

confidence: 99%

The UK National Registry of ABO and HLA Antibody Incompatible Renal Transplantation: Pretransplant Factors Associated With Outcome in 879 Transplants

Pankhurst

Hudson

Mumford

et al. 2017

Transplantation Direct

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BackgroundABO and HLA antibody incompatible (HLAi) renal transplants (AIT) now comprise around 10% of living donor kidney transplants. However, the relationship between pretransplant factors and medium-term outcomes are not fully understood, especially in relation to factors that may vary between centers.MethodsThe comprehensive national registry of AIT in the United Kingdom was investigated to describe the donor, recipient and transplant characteristics of AIT. Kaplan-Meier analysis was used to compare survival of AIT to all other compatible kidney transplants performed in the United Kingdom. Cox proportional hazards regression modeling was used to determine which pretransplant factors were associated with transplant survival in HLAi and ABOi separately. The primary outcome was transplant survival, taking account of death and graft failure.ResultsFor 522 HLAi and 357 ABO incompatible (ABOi) transplants, 5-year transplant survival rates were 71% (95% confidence interval [CI], 66-75%) for HLAi and 83% (95% CI, 78-87%) for ABOi, compared with 88% (95% CI, 87-89%) for 7290 standard living donor transplants, and 78% (95% CI, 77-79%) for 15 322 standard deceased donor transplants (P < 0.0001). Increased chance of transplant loss in HLAi was associated with increasing number of donor specific HLA antibodies, center performing the transplant, antibody level at the time of transplant, and an interaction between donor age and dialysis status. In ABOi, transplant loss was associated with no use of IVIg, cytomegalovirus seronegative recipient, 000 HLA donor-recipient mismatch; and increasing recipient age.ConclusionsResults of AIT were acceptable, certainly in the context of a choice between living donor AIT and an antibody compatible deceased donor transplant. Several factors were associated with increased chance of transplant loss, and these can lead to testable hypotheses for further improving therapy.

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Section: Discussionmentioning

confidence: 99%

The UK National Registry of ABO and HLA Antibody Incompatible Renal Transplantation: Pretransplant Factors Associated With Outcome in 879 Transplants

Pankhurst

Hudson

Mumford

et al. 2017

Transplantation Direct

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“…Two doses of basiliximab 20 mg were given, at days zero and four. The protocol was the same as stated in our previous publications [9], [10].…”

Section: Methodsmentioning

confidence: 99%

Behaviour of Non-Donor Specific Antibodies during Rapid Re-Synthesis of Donor Specific HLA Antibodies after Antibody Incompatible Renal Transplantation

et al. 2013

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BackgroundHLA directed antibodies play an important role in acute and chronic allograft rejection. During viral infection of a patient with HLA antibodies, the HLA antibody levels may rise even though there is no new immunization with antigen. However it is not known whether the converse occurs, and whether changes on non-donor specific antibodies are associated with any outcomes following HLA antibody incompatible renal transplantation.Methods55 patients, 31 women and 24 men, who underwent HLAi renal transplant in our center from September 2005 to September 2010 were included in the studies. We analysed the data using two different approaches, based on; i) DSA levels and ii) rejection episode post transplant. HLA antibody levels were measured during the early post transplant period and corresponding CMV, VZV and Anti-HBs IgG antibody levels and blood group IgG, IgM and IgA antibodies were quantified.ResultsDespite a significant DSA antibody rise no significant non-donor specific HLA antibody, viral or blood group antibody rise was found. In rejection episode analyses, multiple logistic regression modelling showed that change in the DSA was significantly associated with rejection (p = 0.002), even when adjusted for other antibody levels. No other antibody levels were predictive of rejection. Increase in DSA from pre treatment to a post transplant peak of 1000 was equivalent to an increased chance of rejection with an odds ratio of 1.47 (1.08, 2.00).ConclusionIn spite of increases or decreases in the DSA levels, there were no changes in the viral or the blood group antibodies in these patients. Thus the DSA rise is specific in contrast to the viral, blood group or third party antibodies post transplantation. Increases in the DSA post transplant in comparison to pre-treatment are strongly associated with occurrence of rejection.

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“…[23] We do not use IVIg, and have phased out post-transplant plasmapheresis as it is associated with increased complication rates, and is not able to control DSA levels effectively during periods of rapid synthesis. [35]…”

Section: Management Of Antibody-mediated Rejectionmentioning

confidence: 99%

Human leukocyte antigen antibody incompatible renal transplantation

et al. 2012

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Anti-human leukocyte antigen (HLA) antibodies are recognized as an important problem in organ transplant recipients. This is because antibodies formed against a graft months or years after implantations are the major cause of late allograft failure, and also because protocols allow the transplantation of some grafts across pre-formed HLA antibodies. Advances in our understanding of anti-HLA antibody- mediated rejection (AMR) have occurred because of a better understanding of the histological findings during AMR; more sensitive and specific methods to measure anti-HLA antibodies; and through clinical investigation of patients transplanted across an HLA barrier. Despite advances in therapy and investigation, AMR remains a major problem and treatment protocols often fail to treat it successfully. This review aims to describe the issues in each of these areas and to suggest how clinicians may be able to improve the management of patients with anti-HLA antibodies.

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Rises and Falls in Donor-Specific and Third-Party HLA Antibody Levels After Antibody Incompatible Transplantation

Abstract: DSA levels may change markedly in the first month after antibody incompatible transplantation, and the risk of rejection was associated with higher pretreatment and peak levels.

Cited by 36 publications

References 18 publications

The UK National Registry of ABO and HLA Antibody Incompatible Renal Transplantation: Pretransplant Factors Associated With Outcome in 879 Transplants

The UK National Registry of ABO and HLA Antibody Incompatible Renal Transplantation: Pretransplant Factors Associated With Outcome in 879 Transplants

Behaviour of Non-Donor Specific Antibodies during Rapid Re-Synthesis of Donor Specific HLA Antibodies after Antibody Incompatible Renal Transplantation

Human leukocyte antigen antibody incompatible renal transplantation

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