Preprint Case Report Version 1 Preserved in Portico This version is not peer-reviewed

Daratumumab Interferes with Histocompatibility Crossmatch Impacting Immunological Assessment in Solid Organ Transplantation

Chak-Sum Ho
* ORCID logo ,
Kyle R. Putnam
,
Christine R. Peiter
,
Walter Herczyk
,
John A. Gerlach
,
Yee Lu
,
Erica L. Campagnaro
,
Kenneth J. Woodside
,
Matthew F. Cusick
*
Version 1 : Received: 11 September 2022 / Approved: 13 September 2022 / Online: 13 September 2022 (05:48:27 CEST)

A peer-reviewed article of this Preprint also exists.

Ho, C.-S.; Putnam, K.R.; Peiter, C.R.; Herczyk, W.; Gerlach, J.A.; Lu, Y.; Campagnaro, E.L.; Woodside, K.J.; Cusick, M.F. Daratumumab Interferes with Allogeneic Crossmatch Impacting Immunological Assessment in Solid Organ Transplantation. J. Clin. Med. 2022, 11, 6059. Ho, C.-S.; Putnam, K.R.; Peiter, C.R.; Herczyk, W.; Gerlach, J.A.; Lu, Y.; Campagnaro, E.L.; Woodside, K.J.; Cusick, M.F. Daratumumab Interferes with Allogeneic Crossmatch Impacting Immunological Assessment in Solid Organ Transplantation. J. Clin. Med. 2022, 11, 6059.

Abstract

We report the first case of Daratumumab interference of allogeneic crossmatch tests repeatedly causing aberrant false-positive results, which inadvertently delayed transplant for a waitlisted renal patient with multiple myeloma. Daratumumab is an IgG1κ human monoclonal antibody commonly used to treat multiple myeloma, characterized by cancerous plasma cells and often leads to renal failure requiring kidney transplant, by depleting CD38-expressing plasma cells. In this case study, the patient had end-stage renal disease secondary to multiple myeloma and was continuously receiving Daratumumab infusions. The patient did not have any detectable antibodies to human leukocyte antigens but repeatedly had unexpected positive crossmatch by the flow cytometry-based method with 26 of the 27 potential deceased organ donors, implying donor-recipient immunological incompatibility. However, further review and analysis suggested that the positive crossmatches were likely false-positive as a result of interference from Daratumumab binding to donor cell surface CD38 as opposed to the presence of donor-specific antibodies. The observed intensity of the false-positive crossmatches was also highly variable, potentially due to donor- and/or cell-dependent expression of CD38. The variability of CD38 expression was, therefore, for the first time, characterized on the T and B cells isolated from various tissues and peripheral blood of 78 individuals. Overall, T cells were found to have a lower CD38 expression profile than the B cells, and no significant difference was observed between deceased and living individuals. Finally, we show that a simple cell treatment by dithiothreitol can effectively mitigate Daratumumab interference thus preserving the utility of pre-transplant crossmatch in multiple myeloma patients awaiting kidney transplant.

Keywords

Antibody-mediated rejection; Crossmatch; Daratumumab; End-stage renal disease; Flow cytometry; HLA; Multiple myeloma; Transplantation

Subject

Medicine and Pharmacology, Pathology and Pathobiology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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