Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Correspondence
  • Published:

Lack of both donor and recipient anti-EBV T cells in EBV seronegative recipients of grafts from seropositive donors

Bone Marrow Transplantation volume 58, pages 332–333 (2023)Cite this article

Subjects

Post-transplant lymphoproliferative disorder (PTLD) is a life-threatening complication of hematopoietic stem cell transplantation (HCT). It is caused by Epstein-Barr virus (EBV)-infected B cell proliferation which is unopposed by T cells and possibly also NK cells [1, 2]. EBV seronegative recipients receiving grafts from seropositive donors (D + R− patients) are at a particularly high risk of developing PTLD and dying due to PTLD, certainly in comparison to D + R + patients and probably also in comparison to D-R + patients [3,4,5,6]. This is counterintuitive, as for cytomegalovirus (CMV), D-R + patients are at the highest risk of developing CMV disease [7,8,9]. This is due to the lack of transfer of memory/effector anti-CMV T cells with the D- graft, resulting in a slower post-transplant reconstitution of donor-derived anti-CMV T cells in D-R + vs D + R + patients [8, 9]. For EBV, the reason for the D + R− patients being at the highest risk of developing PTLD, especially compared to the most frequent serostatus group of D + R + patients, is unknown.

We hypothesized that EBV D + R + patients harbor recipient-derived, functional, anti-EBV memory/effector T cells surviving transplant conditioning whereas D + R− patients do not, as they did not encounter the virus pretransplant. We also hypothesized that D + R− and D + R + patients harbor similar quantity of donor-derived, functional, anti-EBV memory/effector T cells, as they are expected to have received similar quantity of these cells with the D + graft.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Total (donor + recipient) EBV T cell counts are lower in D + R− (n = 8) than D + R + (n = 24) patients.

Data availability

For the de-identified, original data, please contact the senior author at jstorek@ucalgary.ca.

References

  1. Rasche L, Kapp M, Einsele H, Mielke S. EBV-induced post transplant lymphoproliferative disorders: a persisting challenge in allogeneic hematopoetic SCT. Bone Marrow Transpl. 2014;49:163–7.

    Article  CAS  Google Scholar 

  2. Martinez OM, Krams SM. The Immune Response to Epstein Barr Virus and Implications for Posttransplant Lymphoproliferative Disorder. Transplantation 2017;101:2009–16.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Kinzel M, Dowhan M, Kalra A, Williamson TS, Dabas R, Jamani K, et al. Risk factors for the incidence of and the mortality due to post-transplant lymphoproliferative disorder after hematopoietic cell transplantation. Transplant Cell Ther. 2022,28:53.e1–10.

    Article  Google Scholar 

  4. Uhlin M, Wikell H, Sundin M, Blennow O, Maeurer M, Ringden O, et al. Risk factors for Epstein-Barr virus-related post-transplant lymphoproliferative disease after allogeneic hematopoietic stem cell transplantation. Haematologica 2014;99:346–52.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Sundin M, Le Blanc K, Ringdén O, Barkholt L, Omazic B, Lergin C, et al. The role of HLA mismatch, splenectomy and recipient Epstein-Barr virus seronegativity as risk factors in post-transplant lymphoproliferative disorder following allogeneic hematopoietic stem cell transplantation. Haematologica 2006;91:1059–67.

    PubMed  Google Scholar 

  6. Kalra A, Roessner C, Jupp J, Williamson T, Tellier R, Chaudhry A, et al. Risk factors for post-transplant lymphoproliferative disorder after Thymoglobulin-conditioned hematopoietic cell transplantation. Clin Transplant. 2018;32:e13150.

    Article  Google Scholar 

  7. Kalra A, Williamson T, Daly A, Savoie ML, Stewart DA, Khan F, et al. Impact of Donor and Recipient Cytomegalovirus Serostatus on Outcomes of Antithymocyte Globulin-Conditioned Hematopoietic Cell Transplantation. Biol Blood Marrow Transpl. 2016;22:1654–63.

    Article  CAS  Google Scholar 

  8. Ugarte-Torres A, Hoegh-Petersen M, Liu Y, Zhou F, Williamson TS, Quinlan D, et al. Donor serostatus has an impact on cytomegalovirus-specific immunity, cytomegaloviral disease incidence, and survival in seropositive hematopoietic cell transplant recipients. Biol Blood Marrow Transpl. 2011;17:574–85.

    Article  Google Scholar 

  9. van der Heiden PLJ, van Egmond HM, Veld SAJ, van de Meent M, Eefting M, de Wreede LC, et al. CMV seronegative donors: Effect on clinical severity of CMV infection and reconstitution of CMV-specific immunity. Transpl Immunol. 2018;49:54–8.

    Article  PubMed  Google Scholar 

  10. Hoegh-Petersen M, Goodyear D, Geddes MN, Liu S, Ugarte-Torres A, Liu Y, et al. High incidence of post transplant lymphoproliferative disorder after antithymocyte globulin-based conditioning and ineffective prediction by day 28 EBV-specific T lymphocyte counts. Bone Marrow Transpl. 2011;46:1104–12.

    Article  CAS  Google Scholar 

  11. Djaoud Z, Guethlein LA, Horowitz A, Azzi T, Nemat-Gorgani N, Olive D, et al. Two alternate strategies for innate immunity to Epstein-Barr virus: One using NK cells and the other NK cells and γδ T cells. J Exp Med. 2017;214:1827–41.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Hatton O, Strauss-Albee DM, Zhao NQ, Haggadone MD, Pelpola JS, Krams SM, et al. NKG2A-Expressing Natural Killer Cells Dominate the Response to Autologous Lymphoblastoid Cells Infected with Epstein-Barr Virus. Front Immunol. 2016;7:607.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

This study was supported by grant funding from the Alberta Cancer Foundation and Buckley Family Charitable Foundation. We thank the Clinical Research Unit staff, particularly Mamta Kantharia and Krista Dyck, for assistance with blood specimen collection, and Khan/Storek lab staff, particularly Cindy Miskolczi and Paria Ziaiy, for specimen processing and storage. We also thank the Alberta Blood and Marrow Transplant physicians (led by Dr Mona Shafey), inpatient nurses (led by Lorraine Harrison), and outpatient nurses (led by Alexis Desautels) for their invaluable help with specimen collection.

Author information

Authors and Affiliations

  1. Cumming School of Medicine, University of Calgary, Calgary, AB, Canada

    Megan Kinzel, Amit Kalra, Gaurav Tripathi, Poonam Dharmani-Khan, Faisal Khan & Jan Storek

  2. Alberta Precision Labs, Calgary, AB, Canada

    Poonam Dharmani-Khan & Faisal Khan

Authors
  1. Megan Kinzel
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Amit Kalra
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Gaurav Tripathi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Poonam Dharmani-Khan
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Faisal Khan
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jan Storek
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

MK collected and analyzed the data and wrote the paper. AK and GT assisted with study design, data collection, and data analysis. PDK and FK provided scientific input. JS designed the project (along with MK), supervised the study and data analysis, and helped write the paper. All authors reviewed and approved the final paper. This work was completed in partial fulfilment of the requirements for the degree of Bachelor of Health Sciences Honours.

Corresponding author

Correspondence to Megan Kinzel.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kinzel, M., Kalra, A., Tripathi, G. et al. Lack of both donor and recipient anti-EBV T cells in EBV seronegative recipients of grafts from seropositive donors. Bone Marrow Transplant 58, 332–333 (2023). https://doi.org/10.1038/s41409-022-01884-3

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41409-022-01884-3

Search

Advanced search

Quick links