The role of HLA-DP mismatches and donor specific HLA-DP antibodies in kidney transplantation: a case series

Daniëls, Liesbeth; Claas, Frans H.J.; Senev, Aleksandar; Driessche, Marleen Vanden; Emonds, Marie‐Paule; Laecke, Steven Van; Hellemans, Rachel; Abramowicz, Daniel; Naesens, Maarten

doi:10.1016/j.trim.2020.101287

Cited by 19 publications

(25 citation statements)

References 30 publications

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“…A recent study reported that patients with isolated pre-transplant DSA F I G U R E 3 Effect of HLA-DPB1 Terasaki epitope (TerEp) mismatches (n = 0, 1, or ≥2) on kidney graft survival against HLA-DP eplets had an increased risk for ABMR, but no conclusion could be made regarding an association of post-transplant de novo HLA-DP DSA with ABMR because to rarity of events with isolated de novo HLA-DP DSA found in their cohort. 7 In our study, regrettably, there were no data on infections (e.g., BK virus and cytomegalovirus), adherence, and so forth, available to us which could be explored to identify the likely reason for the poorer graft survival in patients with HLA-DPB1 eplet or TerEp mismatches. We cannot explain why eplet mismatches and TerEp mismatches had deleterious influence on graft survival.…”

Section: Discussionmentioning

confidence: 85%

“…There have been only few reports specifically looking at dnDSA against HLA-DPB1. [7][8][9] Most studies described the detection of HLA-DPB1 antibodies in transplanted patients without separating DSA versus non-DSA or preformed versus de novo antibodies. [10][11][12] In addition, the impact of de novo DPB1-DSA on graft survival was controversially discussed, often based on case reports only.…”

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confidence: 99%

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Analysis of de novo donor‐specific HLA‐DPB1 antibodies in kidney transplantation

Tang

Unterrainer

Fink

et al. 2021

HLA

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HLA matching and avoidance of unacceptable mismatches are important aspects in the selection of donors for solid organ transplantation. The impact of HLA-DPB1 incompatibility on the outcomes of kidney transplantation is not fully understood. We investigated a potential effect of mismatching for HLA-DPB1 at allele, eplet, or Terasaki epitope (TerEp) level on the formation of de novo donor-specific antibodies (dnDSA) and also asked whether polymorphisms associated with HLA-DPB1 expression level may influence dnDSA induction. Furthermore, we analyzed the correlation between graft survival and HLA-DPB1 mismatches defined by different approaches.

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Section: Discussionmentioning

confidence: 85%

mentioning

confidence: 99%

Analysis of de novo donor‐specific HLA‐DPB1 antibodies in kidney transplantation

Tang

Unterrainer

Fink

et al. 2021

HLA

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“…We undertook specific subgroup analyses to better understand the lower graft survival in patients with cPRA $98%, including stratified analyses in first and repeat transplant recipients and an analysis of living related transplant recipients. These subgroup analyses suggest the most likely explanation for the higher risk of graft loss in patients with cPRA $98% is the presence of unrecognized preformed DSA, despite our study design of matching donor-recipient pairs at HLA-A, B, DR, and DQB1; the fact that cPRA was not associated with graft survival in first transplant recipients suggests the potential importance of antibodies to HLA-DP, DQA, and Cw antigens, which were not included in the US cPRA calculator during the study timeframe but can have a deleterious effect in kidney transplantation (24)(25)(26). These antibodies may be more frequent in repeat transplant recipients (27)(28)(29).…”

Section: Discussionmentioning

confidence: 99%

Pretransplant Calculated Panel Reactive Antibody in the Absence of Donor-Specific Antibody and Kidney Allograft Survival

Lan

Kadatz

Chang

et al. 2021

CJASN

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Background and objectivesPanel reactive antibody informs the likelihood of finding an HLA-compatible donor for transplant candidates, but has historically been associated with acute rejection and allograft survival because testing methods could not exclude the presence of concomitant donor-specific antibodies. Despite new methods to exclude donor-specific antibodies, panel reactive antibody continues to be used to determine the choice of induction and maintenance immunosuppression. The study objective was to determine the clinical relevance of panel reactive antibody in the absence of donor-specific antibodies.Design, setting, participants, & measurementsRetrospective observational study of kidney allograft survival among 4058 zero HLA-A–, B-, DR-, and DQB1-mismatched transplant recipients without antibodies to donor kidney antigens encoded by these HLA gene loci.ResultsAmong 4058 first and repeat transplant recipients, patients with calculated panel reactive antibody (cPRA) 1%–97% were not at higher risk of transplant failure, compared with patients with cPRA of 0% (death censored graft loss: hazard ratio, 1.07; 95% confidence interval, 0.82 to 1.41). Patients with cPRA ≥98% had a higher risk of graft loss from any cause including death (hazard ratio, 1.39; 95% confidence interval, 1.08 to 1.79) and death censored allograft failure (hazard ratio, 1.78; 95% confidence interval, 1.27 to 2.49). In stratified analyses, the higher risk of graft loss among patients with cPRA ≥98% was only observed among repeat, but not first, transplant recipients. In subgroup analysis, there was no association between cPRA and graft loss among living related transplant recipients.ConclusionsCalculated panel reactive antibody is poorly associated with post-transplant immune reactivity to the allograft in the absence of donor-specific antibody.PodcastThis article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2021_01_25_CJN13640820_final.mp3

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“…Recent studies have evaluated the association between MFI of HLA-DP antibodies and the results of flow cytometric crossmatch (FCXM) [ 9 , 10 ]. Simmons et al analyzed FCXM results in nine patients with HLA-DP antibodies and found that two patients with HLA-DP antibodies with MFI > 8000 had positive crossmatches [ 10 ].…”

Section: Discussionmentioning

confidence: 99%

“…On the other hand, FCXM results were negative for 7 patients with MFI of HLA-DP antibodies ranging from 3000 to 8000. A multicenter study in Belgium investigated 20 FCXM using sera with HLA-DPB1 antibodies [ 9 ]. Three positive FCXM results were detected.…”

Section: Discussionmentioning

confidence: 99%

Misidentification of preformed anti-HLA-DP antibodies leads to antibody-mediated kidney transplant rejection: a case report

et al. 2022

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Background Patients who are HLA-sensitized are at high risk for early antibody-mediated rejection (AMR) and worse outcomes. Therefore, it is crucial to detect the presence of donor-specific antibodies (DSAs) using pretransplant antibody identification and crossmatch assays. An error in antibody identification can lead to disastrous clinical outcomes. We present a case of acute AMR associated with preformed HLA-DPα and HLA-DPβ DSAs that were not identified before transplantation. Case presentation A 27-year-old woman received a second kidney transplant from a deceased donor. Her pretransplant panel-reactive antibody level was 94%. The complement-dependent cytotoxicity crossmatch was negative for T and B cells at the time of transplantation. She experienced early acute AMR proven by a kidney biopsy. Single antigen bead testing of the patient’s serum at the time of rejection as well as the pre-second transplant serum revealed strong antibodies against the DPA1*01:03 and DPB1*02:01 alleles in the second donor. These antibodies were not identified by phenotypic bead assay during the patient’s time on the waiting list. The patient was treated with plasmapheresis and anti-thymocyte globulin. However, she experienced abdominal pain on day 37 post-transplantation. Surgical exploration revealed a laceration on the transplanted kidney, which was then repaired. Subsequently, infected hematoma was suspected and the transplanted kidney was removed. Conclusion The present case highlights the clinical significance of preformed HLA-DPα and HLA-DPβ DSAs. Accuracy in determination of HLA antibodies before transplantattion is critical for transplant outcome. HLA-DP typing and single antigen bead testing are recommended for a precise antibody interpretation, especially in highly sensitized patients. Careful interpretation of antibody testing results is essential for the success of organ transplantation.

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The role of HLA-DP mismatches and donor specific HLA-DP antibodies in kidney transplantation: a case series

Cited by 19 publications

References 30 publications

Analysis of de novo donor‐specific HLA‐DPB1 antibodies in kidney transplantation

Analysis of de novo donor‐specific HLA‐DPB1 antibodies in kidney transplantation

Pretransplant Calculated Panel Reactive Antibody in the Absence of Donor-Specific Antibody and Kidney Allograft Survival

Misidentification of preformed anti-HLA-DP antibodies leads to antibody-mediated kidney transplant rejection: a case report

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