Rebound and overshoot of donor‐specific antibodies to human leukocyte antigens (HLA) during desensitization with plasma exchanges in hematopoietic progenitor cell transplantation: A case report

Abstract

BackgroundDonor‐specific antibodies (DSA) to HLA have been associated with graft loss in hematopoietic progenitor cell (HPC) transplantation. Limited data associate therapeutic plasma exchange (TPE) with desensitization and successful engraftment. We report an attempt of desensitization and observed overshooting of DSA during transplantation.Case report and resultsA 27‐year‐old female with cutaneous T cell lymphoma was scheduled for HPC transplantation from her HLA‐haploidentical half‐sister, who carried the HLA‐DRB1*13:03:01 allele. The patient had the corresponding DSA. Lacking an alternative donor option at the time, we attempted a desensitization approach by immunosuppression with tacrolimus and mycophenolate mofetil (MMF). Unexpectedly, DSA increased from a mean fluorescence intensity (MFI) of 1835 on day −63 to 9008 on day −7. The MFI increased further during 3 TPE procedures and intravenous immunoglobulin (IVIG) until day −1. After transplantation, the DSA remained elevated despite 2 more TPE/IVIG procedures and graft‐versus‐host disease prophylaxis with high‐dose cyclophosphamide, sirolimus, and MMF. Flow cytometric crossmatch, initially negative, turned positive after transplantation. Primary graft failure occurred and was attributed to antibody‐mediated rejection. A second transplantation from a 7/8 HLA‐matched unrelated donor, not carrying DRB1*13:03 allele, resulted in successful engraftment.ConclusionUnexpected and rapid increases of a DSA can occur despite the use of current desensitization approaches. This is problematic when conditioning has already started, as such increases are unlikely to be overcome by TPE or other interventions for desensitization. Overshoot of DSA in HPC transplantation has rarely been reported. Its cause remains unclear and can include underlying disease, immunotherapy, chemotherapy, or TPE.

Primary oxidative phosphorylation defects lead to perturbations in the human B cell repertoire

“…Amongst the most significantly affected populations (i.e., population density and MTRNR2L8 expression) in our scRNAseq studies, were constituents of the humoral immune response, specifically B cells and plasma cells. During B cell activation and differentiation, multiple cellular processes ensure that B cells recognize a diverse array of microbial antigens (i.e., >10 12) , undergo exponential expansion, and differentiate into effector cells (49). These characteristics of the polyclonal B cell response increase the probability of recognizing an antigen (33) and exerts a protective effect.…”

“…Low to intermediate resolution HLA typing was performed for HLA class II loci (HLA-DRB1, -DQB1, -DRB3, -DRB4, -DRB5) with sequence specific oligonucleotide (SSO) probes (LABType SSO; One Lambda, Canoga Park, CA) (12). The fluorescent intensity of phycoerythrin on each microsphere (applying the Luminex bead technology; Luminex, Austin, TX) was measured with a flow cytometer (LABScan3D, Luminex FLEXMAP 3D; One Lambda).…”

Liver Transplantation from a Human Leukocyte Antigen-Matched Sibling Donor: Effectiveness of Direct-Acting Antiviral Therapy against Hepatitis C Virus Infection

“…DSA to HLA have been associated with graft loss in hematopoietic progenitor cell transplantation [23]. The presence of mismatched antigens and epitopes might relate directly to the development of de novo DSA and rejection [24].…”

Recent Advancements in Poor Graft Function Following Hematopoietic Stem Cell Transplantation

“…In a case report by Hassan et al. ( 84 ), during hematopoietic progenitor cell transplantation, DSA unexpectedly rebounded and rapidly increased during desensitization with repeated plasma exchange and immunoglobulin, finally leading to primary PGF. However, the cause of this phenomenon remains unclear.…”