The Importance of Anti-HLA-Specific Antibody Strength in Monitoring Kidney Transplant Patients

Mizutani, Kazuo; Terasaki, Paul I.; Hamdani, E.; Esquenazi, Violet; Rosén, Anne; Miller, John S.; Ozawa, Miyuki

doi:10.1111/j.1600-6143.2006.01721.x

Cited by 120 publications

(84 citation statements)

References 8 publications

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“…Not only the specificity but also the strength of the antibody can be determined in a Luminex test by MFI or molecules of equivalent soluble fluorochrome (MESF) values (Figure 1). The titers of the anti-HLA antibodies were correlated with MESF values (56). An increasing number of recent studies demonstrated an association between the strength of DSAs and risk of development of AMR, response to treatment of AMR, allograft survival, and success of desensitization protocols.…”

Section: Current Problems In Desensitization Protocolsmentioning

confidence: 96%

Desensitization Protocols and Their Outcome

Marfo

Ling

et al. 2011

Clinical Journal of the American Society of Nephrology

234

184

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SummaryIn the last decade, transplantation across previously incompatible barriers has increasingly become popular because of organ donor shortage, availability of better methods of detecting and characterizing anti-HLA antibodies, ease of diagnosis, better understanding of antibody-mediated rejection, and the availability of effective regimens. This review summarizes all manuscripts published since the first publication in 2000 on desensitized patients and discusses clinical outcomes including acute and chronic antibody-mediated rejection rate, the new agents available, kidney paired exchange programs, and the future directions in sensitized patients. There were 21 studies published between 2000 and 2010, involving 725 patients with donor-specific anti-HLA antibodies (DSAs) who underwent kidney transplantation with different desensitization protocols. All studies were single center and retrospective. The patient and graft survival were 95% and 86%, respectively, at a 2-year median follow-up. Despite acceptable short-term patient and graft survivals, acute rejection rate was 36% and acute antibody-mediated rejection rate was 28%, which is significantly higher than in nonsensitized patients. Recent studies with longer follow-up of those patients raised concerns about long-term success of desensitization protocols. The studies utilizing protocol biopsies in desensitized patients also reported higher subclinical and chronic antibody-mediated rejection. An association between the strength of DSAs determined by median fluorescence intensity values of Luminex single-antigen beads and risk of rejection was observed. Two new agents, bortezomib, a proteasome inhibitor, and eculizumab, an anti-complement C5 antibody, were recently introduced to desensitization protocols. An alternative intervention is kidney paired exchange, which should be considered first for sensitized patients.

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Section: Current Problems In Desensitization Protocolsmentioning

confidence: 96%

Desensitization Protocols and Their Outcome

Marfo

Ling

et al. 2011

Clinical Journal of the American Society of Nephrology

234

184

View full text Add to dashboard Cite

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“…These antibodies can be detected with the complement‐dependent cytotoxicity crossmatch assay (CDC‐XM), which has been the gold standard since 1969. With the more recently developed single antigen bead (SAB) assays, DSAs can be detected with increased sensitivity and specificity,9 but the relation between these SAB assay–detected antibodies and clinical outcome is still unclear 10, 11, 12, 13, 14. The presence of SAB assay–detected antibodies that do not cause a positive CDC‐XM is not a contraindication for transplant but may indicate an increased immunological risk for rejection and allograft loss 15…”

Section: Introductionmentioning

confidence: 99%

Differential effects of donor-specific HLA antibodies in living versus deceased donor transplant

Kamburova

Wisse

Joosten

et al. 2018

American Journal of Transplantation

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The presence of donor‐specific anti‐HLA antibodies (DSAs) is associated with increased risk of graft failure after kidney transplant. We hypothesized that DSAs against HLA class I, class II, or both classes indicate a different risk for graft loss between deceased and living donor transplant. In this study, we investigated the impact of pretransplant DSAs, by using single antigen bead assays, on long‐term graft survival in 3237 deceased and 1487 living donor kidney transplants with a negative complement‐dependent crossmatch. In living donor transplants, we found a limited effect on graft survival of DSAs against class I or II antigens after transplant. Class I and II DSAs combined resulted in decreased 10‐year graft survival (84% to 75%). In contrast, after deceased donor transplant, patients with class I or class II DSAs had a 10‐year graft survival of 59% and 60%, respectively, both significantly lower than the survival for patients without DSAs (76%). The combination of class I and II DSAs resulted in a 10‐year survival of 54% in deceased donor transplants. In conclusion, class I and II DSAs are a clear risk factor for graft loss in deceased donor transplants, while in living donor transplants, class I and II DSAs seem to be associated with an increased risk for graft failure, but this could not be assessed due to their low prevalence.

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“…3 Studies of the clinical relevance of HLA-DSA in patients who receive a transplant with a negative CXM have been contradictory. 6 -9 The ability to quantify these antibodies 10 has added a dimension of complexity to the equation. The semiquantitative ELISA technique was used to advantage by our group in a cohort of 237 patients with renal transplants, showing an increase in the occurrence of acute antibody-mediated rejection (AMR) with increasing HLA-DSA levels detected in historic sera.…”

mentioning

confidence: 99%

Preexisting Donor-Specific HLA Antibodies Predict Outcome in Kidney Transplantation

Lefaucheur¹,

Loupy²,

Hill³

et al. 2010

Journal of the American Society of Nephrology

709

567

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The clinical importance of preexisting HLA antibodies at the time of transplantation, identified by contemporary techniques, is not well understood. We conducted an observational study analyzing the association between preexisting donor-specific HLA antibodies (HLA-DSA) and incidence of acute antibody-mediated rejection (AMR) and survival of patients and grafts among 402 consecutive deceaseddonor kidney transplant recipients. We detected HLA-DSA using Luminex single-antigen assays on the peak reactive and current sera. All patients had a negative lymphocytotoxic cross-match test on the day of transplantation. We found that 8-year graft survival was significantly worse (61%) among patients with preexisting HLA-DSA compared with both sensitized patients without HLA-DSA (93%) and nonsensitized patients (84%). Peak HLA-DSA Luminex mean fluorescence intensity (MFI) predicted AMR better than current HLA-DSA MFI (P ϭ 0.028). As MFI of the highest ranked HLA-DSA detected on peak serum increased, graft survival decreased and the relative risk for AMR increased: Patients with MFI Ͼ6000 had Ͼ100-fold higher risk for AMR than patients with MFI Ͻ465 (relative risk 113; 95% confidence interval 31 to 414). The presence of HLA-DSA did not associate with patient survival. In conclusion, the risk for both AMR and graft loss directly correlates with peak HLA-DSA strength. Quantification of HLA antibodies allows stratification of immunologic risk, which should help guide selection of acceptable grafts for sensitized patients.

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The Importance of Anti-HLA-Specific Antibody Strength in Monitoring Kidney Transplant Patients

Cited by 120 publications

References 8 publications

Desensitization Protocols and Their Outcome

Desensitization Protocols and Their Outcome

Differential effects of donor-specific HLA antibodies in living versus deceased donor transplant

Preexisting Donor-Specific HLA Antibodies Predict Outcome in Kidney Transplantation

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