Memory B-cell derived donor-specific antibodies do not predict outcome in sensitized kidney transplant recipients: a retrospective single-center study

Frontiers in Immunology, vol. 15, pp. 1360627

Abstract

Background: Repeated exposure to sensitizing events can activate HLA-specific memory B cells, leading to the production of donor-specific memory B cell antibodies (DSAm) that pose a risk for antibody-mediated rejection (ABMR) in kidney transplant recipients (KTRs). This single-center retrospective study aimed to identify DSAm and assess their association with outcomes in a cohort of KTRs with pretransplant serum donor-specific antibodies (DSA). Methods: We polyclonally activated pretransplant peripheral blood mononuclear cells (PBMCs) from 60 KTRs in vitro, isolated and quantified IgG from the culture supernatant using ELISA, and analyzed the HLA antibodies of eluates with single antigen bead (SAB) assays, comparing them to the donor HLA typing for potential DSAm. Biopsies from 41 KTRs were evaluated for rejection based on BANFF 2019 criteria. Results: At transplantation, a total of 37 DSAm were detected in 26 of 60 patients (43%), of which 13 (35%) were found to be undetectable in serum. No significant association was found between pretransplant DSAm and ABMR (P=0.53). Similar results were observed in a Kaplan-Meier analysis for ABMR within the first year posttransplant (P=0.29). Additionally, MFI levels of DSAm showed no significant association with ABMR (P=0.28). Conclusion: This study suggests no significant association between DSAm and biopsy-proven clinical ABMR. Further prospective research is needed to determine whether assessing DSAm could enhance existing immunological risk assessment methods for monitoring KTRs, particularly in non-sensitized KTRs.

Authors 14

1. Dania Altulea corresponding

   University Medical Center Groningen · University of Groningen

   Affiliation as printed

   Division of Nephrology, Department of Internal Medicine, University Medical Center Groningen, University of Groningen, Groningen, Netherlands

2. Joost C. van den Born

   University Medical Center Groningen · University of Groningen

   Affiliation as printed

   Division of Nephrology, Department of Internal Medicine, University Medical Center Groningen, University of Groningen, Groningen, Netherlands

3. Arjan Diepstra

   University Medical Center Groningen · University of Groningen

   Affiliation as printed

   Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Groningen, Netherlands

4. Laura B Bungener

   University Medical Center Groningen · University of Groningen

   Affiliation as printed

   Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Groningen, Netherlands

   Transplantation Immunology, Department of Laboratory Medicine, University Medical Center Groningen, University of Groningen, Groningen, Netherlands

5. Dagmar Terpstra

   University Medical Center Groningen · University of Groningen

   Affiliation as printed

   Division of Nephrology, Department of Internal Medicine, University Medical Center Groningen, University of Groningen, Groningen, Netherlands

6. Bouke G. Hepkema

   University Medical Center Groningen · University of Groningen

   Affiliation as printed

   Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Groningen, Netherlands

   Transplantation Immunology, Department of Laboratory Medicine, University Medical Center Groningen, University of Groningen, Groningen, Netherlands

7. Rosa G. M. Lammerts

   University Medical Center Groningen · University of Groningen

   Affiliation as printed

   Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Groningen, Netherlands

   Transplantation Immunology, Department of Laboratory Medicine, University Medical Center Groningen, University of Groningen, Groningen, Netherlands

8. Peter Heeringa

   University Medical Center Groningen · University of Groningen

   Affiliation as printed

   Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Groningen, Netherlands

9. Sebastiaan Heidt Aachen Department of Immunology, Leiden University Medical Center

   Leiden University Medical Center

   Affiliation as printed

   Department of Immunology, Leiden University Medical Center, Leiden, Netherlands

10. Henny G. Otten

    University Medical Center Utrecht

    Affiliation as printed

    Center of Translational Immunology, University Medical Center Utrecht (UMC Utrecht), Utrecht, Netherlands

11. Leon C. Reteig

    University Medical Center Utrecht

    Affiliation as printed

    Center of Translational Immunology, University Medical Center Utrecht (UMC Utrecht), Utrecht, Netherlands

12. Gonca E. Karahan Aachen Department of Immunology, Leiden University Medical Center

    Leiden University Medical Center

    Affiliation as printed

    Department of Immunology, Leiden University Medical Center, Leiden, Netherlands

13. Stefan P. Berger

    University Medical Center Groningen · University of Groningen

    Affiliation as printed

    Division of Nephrology, Department of Internal Medicine, University Medical Center Groningen, University of Groningen, Groningen, Netherlands

14. Jan‐Stephan Sanders

    University Medical Center Groningen · University of Groningen

    Affiliation as printed

    Division of Nephrology, Department of Internal Medicine, University Medical Center Groningen, University of Groningen, Groningen, Netherlands