The impact of pre-transplant donor specific antibodies on the outcome of kidney transplantation - Data from the Swiss transplant cohort study.

Frischknecht, Lukas; Deng, Yun; Wehmeier, Caroline; de Rougemont, Olivier; Villard, Jean; Ferrari-Lacraz, Sylvie; Golshayan, Déla; Gannagé, Monique; Binet, Isabelle; Wirthmüller, Urs; Sidler, Daniel; Schachtner, Thomas; Schaub, Stefan; Nilsson, Jakob (2022). The impact of pre-transplant donor specific antibodies on the outcome of kidney transplantation - Data from the Swiss transplant cohort study. Frontiers in immunology, 13, p. 1005790. Frontiers Research Foundation 10.3389/fimmu.2022.1005790

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Background

Pre-transplant donor specific antibodies (DSA), directed at non-self human leukocyte antigen (HLA) protein variants present in the donor organ, have been associated with worse outcomes in kidney transplantation. The impact of the mean fluorescence intensity (MFI) and the target HLA antigen of the detected DSA has, however, not been conclusively studied in a large cohort with a complete virtual cross-match (vXM).

Methods

We investigated the effect of pre-transplant DSA on the risk of antibody-mediated rejection (ABMR), graft loss, and the rate of eGFR decline in 411 DSA positive transplants and 1804 DSA negative controls.

Results

Pre-transplant DSA were associated with a significantly increased risk of ABMR, graft loss, and accelerated eGFR decline. DSA directed at Class I and Class II HLA antigens were strongly associated with increased risk of ABMR, but only DSA directed at Class II associated with graft loss. DSA MFI markedly affected outcome, and Class II DSA were associated with ABMR already at 500-1000 MFI, whereas Class I DSA did not affect outcome at similar low MFI values. Furthermore, isolated DSA against HLA-DP carried comparable risks for ABMR, accelerated eGFR decline, and graft loss as DSA against HLA-DR.

Conclusion

Our results have important implications for the construction and optimization of vXM algorithms used within organ allocation systems. Our data suggest that both the HLA antigen target of the detected DSA as well as the cumulative MFI should be considered and that different MFI cut-offs could be considered for Class I and Class II directed DSA.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Dermatology, Urology, Rheumatology, Nephrology, Osteoporosis (DURN) > Clinic of Nephrology and Hypertension
04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Institute of Clinical Chemistry

UniBE Contributor:

Wirthmüller, Urs, Sidler, Daniel (A)

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1664-3224

Publisher:

Frontiers Research Foundation

Language:

English

Submitter:

Pubmed Import

Date Deposited:

11 Oct 2022 12:42

Last Modified:

29 Mar 2023 23:38

Publisher DOI:

10.3389/fimmu.2022.1005790

PubMed ID:

36211367

Uncontrolled Keywords:

abmr donor specific antibodies graft loss kidney transplantation virtual cross-match

BORIS DOI:

10.48350/173647

URI:

https://boris.unibe.ch/id/eprint/173647

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