Causes of Positive Pretransplant Crossmatches in the Absence of Donor-Specific Anti-Human Leukocyte Antigen Antibodies: A Single-Center Experience

Kang, Hyunhye; Yoo, Jaeeun; Lee, Sang Yoon; Oh, Eun‐Jee

doi:10.3343/alm.2021.41.4.429

Cited by 12 publications

(9 citation statements)

References 17 publications

(20 reference statements)

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“…Clinically, the importance of this FXM positivity is unknown in the absence of any HLA DSA should not exclude a patient to transplant. Some studies have looked at non‐HLA auto‐antibodies as an explanation to this FXM reactivity in the absence of any HLA DSA 22,23 . However, the role of non‐HLA auto‐antibodies on risk of rejection in lung transplantation needs to be further investigated.…”

Section: Discussionmentioning

confidence: 99%

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The clinical utility and thresholds of virtual and Halifaster flow crossmatches in lung transplantation

Hiho

Levvey

Carroll

et al. 2022

HLA

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Immune sensitization, defined as the presence of alloreactive donor‐specific antibodies (DSA), is associated with increased wait‐times and inferior transplant outcomes. Identifying pretransplant DSA with a physical cell‐based assay is critical in defining immunological risk. However, improved solid phase antibody detection has provided the potential to forgo this physical assay. Here, we evaluated the association between DSA mean fluorescence intensity (MFI) and the recently introduced Halifaster Flow cytometry crossmatch (FXM) to determine if MFI could predict the outcome of FXM and whether a virtual crossmatch (VXM) would provide an accurate risk assessment. Sera from 134 waitlisted lung patients was retrospectively assessed by Halifaster FXM against lymphocytes preparations from 32 donors, resulting in 265 FXMs. HLA typing was performed to 2‐field allelic level and Luminex single antigen beads (SAB) used to identify DSA. The association between FXM and Luminex MFI was calculated using ROC analysis. MFI threshold accuracy was confirmed using a separate validation cohort (174 recipient sera and 34 donors), whereby both VXM and FXMs were compared. From the 265 FXM performed, 48 (18%) T‐cell (TFXM) and 56 (21%) B‐cell (BFXM) were positive. In the evaluation cohort, MFI thresholds of 2000 for HLA‐A, B, DRB1, and > 4000 for DQB1, were predictive of a positive FXM. The validation cohort of 233 paired FXM and VXM confirmed these MFI thresholds for both TFXM and BFXM with an accuracy of 91.4% and 89.3%, respectively. A positive VXM, defined with HLA‐specific MFI thresholds predicts Halifaster FXM reactivity, and can potentially expedite organ allocation, by minimizing the need for the more time‐consuming FXM.

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Section: Discussionmentioning

confidence: 99%

“…Some studies have looked at non-HLA auto-antibodies as an explanation to this FXM reactivity in the absence of any HLA DSA. 22,23 However, the role of non-HLA auto-antibodies on risk of rejection in lung transplantation needs to be further investigated.…”

Section: Discussionmentioning

confidence: 99%

The clinical utility and thresholds of virtual and Halifaster flow crossmatches in lung transplantation

Hiho

Levvey

Carroll

et al. 2022

HLA

View full text Add to dashboard Cite

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“…HLA typing for DRB*3/4/5 was not performed. The detection of DSA was performed by using LABScreen Single Antigen (One Lambda Inc., A Thermo Fisher Scientific Brand, Canoga Park, CA, USA) as described in previous studies [44,45]. EDTA treatment was used to prevent the prozone effect.…”

Section: Hla Typing Antibody Screening and Eplet Analysismentioning

confidence: 99%

Combined Analysis of HLA Class II Eplet Mismatch and Tacrolimus Levels for the Prediction of De Novo Donor Specific Antibody Development in Kidney Transplant Recipients

Lee

Min

Kang

et al. 2022

IJMS

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We investigated whether HLA class II eplet mismatch was related to dnDSA development and analyzed its combined impact with tacrolimus levels for kidney transplantation outcomes. A total of 347 kidney transplants were included. HLA Matchmaker was used for the single molecular eplet, total eplet, antibody (Ab)-verified eplet mismatch analyses, and Ab-verified single molecular analysis to identify HLA-DR/DQ molecular thresholds for the risk of dnDSA development. A time-weighted tacrolimus trough level (TAC-C0) of 5 ng/mL and a TAC-C0 time-weighted coefficient variability (TWCV) of 20% were applied to find the combined effects on dnDSA development. A high level of mismatch for single molecular eplet (DQ ≥ 10), total eplet (DQ ≥ 12), Ab-verified eplet (DQ ≥ 4), and Ab-verified single molecular eplet (DQ ≥ 4) significantly correlated with HLA class II dnDSA development. Class II dnDSA developed mostly in patients with low TAC-C0 and high eplet mismatch. In the multivariable analyses, low TAC-C0 and high eplet mismatch showed the highest hazard ratio for the development of dnDSA. No significant combined effect was observed in dnDSA development according to TWCV. In conclusion, the determination of HLA class II eplet mismatch may improve the risk stratification for dnDSA development, especially in conjunction with tacrolimus trough levels.

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“…4 Development of donor-specific antibodies (DSA) or increase of DSA level can induce a positive crossmatch result and mandates pretransplant desensitization therapy for successful transplantation. [5][6][7] Here, we report a case of successful ABO-incompatible living donor kidney transplantation (ABOi KT) after immunosuppression and desensitization in a patient who developed flow cytometric crossmatch (FCXM)-positive DSA following two doses of COVID-19 vaccination.…”

Section: Introductionmentioning

confidence: 99%

Successful ABO‐incompatible living donor kidney transplantation in a recipient who developed flow cytometry crossmatch‐positive donor‐specific class I HLA antibodies following COVID‐19 vaccination

Kim

Bae

et al. 2022

HLA

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The effects of COVID-19 vaccination on alloimmunization and clinical impact in transplant candidates remain largely unknown. In a 61-year-old man who had no donor-specific antibodies (DSA) and was planned to undergo ABOincompatible kidney transplantation (ABOi KT), DSAs (anti-A24, anti-B51, and anti-Cw14) developed after COVID-19 vaccination. After desensitization therapy, antibody level was further increased, leading to flow cytometric crossmatch-positive status. Donor-specific T cell immunity using interferongamma ELISPOT was continuously negative, whereas SARS-CoV-2 specific T cell immunity was intact. After confirming the C1q-negative status of DSA, the patient received ABOi KT. The patient had stable graft function and suppressed alloimmunity up to 2 months after KT. COVID-19 vaccination might relate to alloimmunization in transplant candidates, and desensitization through immune monitoring can help guide transplantation.

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Causes of Positive Pretransplant Crossmatches in the Absence of Donor-Specific Anti-Human Leukocyte Antigen Antibodies: A Single-Center Experience

Cited by 12 publications

References 17 publications

The clinical utility and thresholds of virtual and Halifaster flow crossmatches in lung transplantation

The clinical utility and thresholds of virtual and Halifaster flow crossmatches in lung transplantation

Combined Analysis of HLA Class II Eplet Mismatch and Tacrolimus Levels for the Prediction of De Novo Donor Specific Antibody Development in Kidney Transplant Recipients

Successful ABO‐incompatible living donor kidney transplantation in a recipient who developed flow cytometry crossmatch‐positive donor‐specific class I HLA antibodies following COVID‐19 vaccination

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