Low levels of human leukocyte antigen donor-specific antibodies detected by solid phase assay before transplantation are frequently clinically irrelevant

Aubert, Vincent; Venetz, Jean-Pierre; Pantaleo, Giuseppe; Pascual, Manuel

doi:10.1016/j.humimm.2009.04.011

Cited by 97 publications

(67 citation statements)

References 20 publications

(23 reference statements)

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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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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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“…Patients with MFI 43000 had a more than 100-fold higher risk of AMR than patients with MFI5465. Aubert et al 7 analyzed a cohort of 113 patients of whom 11/113 (11%) had DSA, and reported that DSA with MFI below 2000 was not associated with shortterm rejection events (cellular and humoral).…”

Section: Discussionmentioning

confidence: 99%

“…However, the clinical relevance of lower levels of DSA is still debated. 6,7 The object of our study was to evaluate long-term graft outcome in patients who had pre-formed HLA DSA. We retrospectively evaluated the presence or absence of HLA antibodies by Luminex solid-phase antibody detection assays in sera collected from patients prior to their kidney transplant, and correlated antibody status pre-transplant with long-term graft outcome.…”

Section: Introductionmentioning

confidence: 99%

Pre-transplant low level HLA antibody shows a composite poor outcome in long-term outcome of renal transplant recipients

Tian

Alberghini

et al. 2015

Renal Failure

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To determine the significance of low-level DSA (donor specific antibody) in patients transplanted with negative cytotoxicity AHG (antihuman immunoglobulin) crossmatch, data from 279 patients who received a kidney transplant between July 1999 and March 2006 were collected. All kidney recipients received ABO-compatible donors. A poor outcome was defined as any one of the following: death, Cr42.0 mmol/L, occurrence of a rejection episode. Luminex Screening and Single Antigen assays from Tepnel Life Codes were used to detect human leukocyte antigen antibodies on pre-transplant sera retrospectively. Twenty-four out of 279 recipients demonstrated the presence of solid-phase DSA (MFI41000) present pre-transplant. In DSA+ group, the accumulated good versus poor outcome rate was 0.30 versus 0.70, respectively. These rates were 0.49 and 0.51, respectively, in the DSAÀ group. The difference in composite poor outcome between DSA+ versus DSAÀ group was significant (p ¼ 0.030). The DSAÀ group had no difference in patient survival as compared to the DSA+ group (p ¼ 0.061). There is no statistically significant difference for either mortality or outcome results between high MFI (42000) and low MFI ( 2000) groups. Our data suggest that solid-phase antibodies which are not strong enough to elicit a positive T-AHG crossmatch may influence long-term graft outcome.

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“…Ten circulating anti-HLA antibodies against major histocompatibility complex class I antigens with mean fluorescence index (MFI) levels between 2000 and 10 000 and 15 anti-HLA antibodies against major histocompatibility complex class II antigens (9 with MFI levels between 2000 and 10 000 and 6 with MFI levels .10 000) were determined by solid phase single-antigen-based testing Luminex assay. 11 A desensitization protocol with monthly IVIg infusions (2 g/kg) had been initiated 6 months earlier, with a progressive decrease in the MFI levels of his circulating anti-HLA class I and II alloantibodies. A second deceased donor kidney transplant was performed on October 24, 2013 in the presence of very low levels of donor-specific antibodies (DSAs) (MFI levels were 100, 232, 523, and 1367, respectively, against mismatched donor antigens DR1, DQ6, DR13, and B62 [15]).…”

Section: Case Reportmentioning

confidence: 99%

Eculizumab to Treat Antibody-Mediated Rejection in a 7-Year-Old Kidney Transplant Recipient

et al. 2015

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We report on successful early eculizumab administration to treat acute antibody-mediated rejection (ABMR) in a highly sensitized kidney transplant recipient. The recipient is a 7-year-old boy who received, 6 months after a desensitization protocol with monthly intravenous immunoglobulin infusion, a second kidney transplant in the presence of low donor-specific antibodies (DSAs). Both pretransplant lymphocytotoxic and flow cytometric crossmatch were negative. Allograft function recovered promptly, with excellent initial function. On postoperative day (POD) 4, the child developed significant proteinuria with an acute rise in serum creatinine. Allograft biopsy showed severe acute ABMR. Intravenous eculizumab (600 mg), preceded by a single session of plasmapheresis, was administered on POD 5 and 12 along with a 4-day thymoglobulin course. After the first dose of eculizumab, a strikingly rapid normalization of allograft function with a decrease in proteinuria occurred. However, because circulating DSA levels remained elevated, the child received 3 doses of intravenous immunoglobulin (POD 15,16,and 17), with a significant subsequent decrease in DSA levels. At 9 months after transplant, the child continues to maintain excellent allograft function with undetectable circulating DSA levels. This unique case highlights the potential efficacy of using early eculizumab to rapidly reverse severe ABMR in pediatric transplantation, and therefore it suggests a novel therapeutic approach to treat acute ABMR.

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Low levels of human leukocyte antigen donor-specific antibodies detected by solid phase assay before transplantation are frequently clinically irrelevant

Cited by 97 publications

References 20 publications

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

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

Pre-transplant low level HLA antibody shows a composite poor outcome in long-term outcome of renal transplant recipients

Eculizumab to Treat Antibody-Mediated Rejection in a 7-Year-Old Kidney Transplant Recipient

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