HLA-DQ Mismatches Lead to More Unacceptable Antigens, Greater Sensitization, and Increased Disparities in Repeat Transplant Candidates
Copyright © 2022 by the American Society of Nephrology..
BACKGROUND: In single-center studies, HLA-DQ mismatches stimulate the most pathogenic donor-specific antibodies. However, because of limitations of transplant registries, this cannot be directly confirmed with registry-based analyses.
METHODS: We evaluated patients in the Scientific Registry of Transplant Recipients who were relisted after renal graft failure with new, unacceptable antigens corresponding to the HLA typing of their previous donor (UA-PD) as a proxy for donor-specific antibodies. Linear regression was applied to estimate the effects of HLA mismatches on UA-PD and the effects of UA-PD on calculated panel reactive antibody (cPRA) values for 4867 kidney recipients from 2010 to 2021.
RESULTS: Each additional HLA-DQ mismatch increased the probability of UA-PD by 25.2% among deceased donor transplant recipients and by 28.9% among living donor transplant recipients, significantly more than all other HLA loci (P<0.05). HLA-DQ UA-PD increased cPRA by 29.0% in living donor transplant recipients and by 23.5% in deceased donor transplant recipients, significantly more than all loci except for HLA-A in deceased donor transplant recipients (23.1%). African American deceased donor transplant recipients were significantly more likely than Hispanic and White recipients to develop HLA-DQ UA-PD; among living donor transplant recipients, African American or Hispanic recipients were significantly more likely to do so compared with White recipients. Models evaluating interactions between HLA-DR/DQ mismatches revealed largely independent effects of HLA-DQ mismatches on HLA-DQ UA-PD.
CONCLUSIONS: HLA-DQ mismatches had the strongest associations with UA-PD, an effect that was greatest in African American and Hispanic recipients. cPRA increases with HLA-DQ UA-PD were equivalent or larger than any other HLA locus. This suggests a need to consider the effects of HLA-DQ in kidney allocation.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:33 |
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| Enthalten in: |
Journal of the American Society of Nephrology : JASN - 33(2022), 12 vom: 30. Dez., Seite 2293-2305 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Isaacson, Dylan [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 02.12.2022 Date Revised 02.12.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1681/ASN.2022030296 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 100 | 1 | |a Isaacson, Dylan |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a HLA-DQ Mismatches Lead to More Unacceptable Antigens, Greater Sensitization, and Increased Disparities in Repeat Transplant Candidates |
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| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2022 by the American Society of Nephrology. | ||
| 520 | |a BACKGROUND: In single-center studies, HLA-DQ mismatches stimulate the most pathogenic donor-specific antibodies. However, because of limitations of transplant registries, this cannot be directly confirmed with registry-based analyses | ||
| 520 | |a METHODS: We evaluated patients in the Scientific Registry of Transplant Recipients who were relisted after renal graft failure with new, unacceptable antigens corresponding to the HLA typing of their previous donor (UA-PD) as a proxy for donor-specific antibodies. Linear regression was applied to estimate the effects of HLA mismatches on UA-PD and the effects of UA-PD on calculated panel reactive antibody (cPRA) values for 4867 kidney recipients from 2010 to 2021 | ||
| 520 | |a RESULTS: Each additional HLA-DQ mismatch increased the probability of UA-PD by 25.2% among deceased donor transplant recipients and by 28.9% among living donor transplant recipients, significantly more than all other HLA loci (P<0.05). HLA-DQ UA-PD increased cPRA by 29.0% in living donor transplant recipients and by 23.5% in deceased donor transplant recipients, significantly more than all loci except for HLA-A in deceased donor transplant recipients (23.1%). African American deceased donor transplant recipients were significantly more likely than Hispanic and White recipients to develop HLA-DQ UA-PD; among living donor transplant recipients, African American or Hispanic recipients were significantly more likely to do so compared with White recipients. Models evaluating interactions between HLA-DR/DQ mismatches revealed largely independent effects of HLA-DQ mismatches on HLA-DQ UA-PD | ||
| 520 | |a CONCLUSIONS: HLA-DQ mismatches had the strongest associations with UA-PD, an effect that was greatest in African American and Hispanic recipients. cPRA increases with HLA-DQ UA-PD were equivalent or larger than any other HLA locus. This suggests a need to consider the effects of HLA-DQ in kidney allocation | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a cadaver organ transplantation | |
| 650 | 4 | |a chronic rejection | |
| 650 | 4 | |a end stage renal disease | |
| 650 | 4 | |a kidney donation | |
| 650 | 4 | |a kidney transplantation | |
| 650 | 4 | |a organ transplant | |
| 650 | 4 | |a renal transplantation | |
| 650 | 4 | |a transplant outcomes | |
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| 650 | 4 | |a transplantation | |
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| 650 | 7 | |a HLA-DQ Antigens |2 NLM | |
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| 700 | 1 | |a Kosmoliaptsis, Vasilis |e verfasserin |4 aut | |
| 700 | 1 | |a Tambur, Anat R |e verfasserin |4 aut | |
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