Transfer of HLA-Specific Allosensitization From a Highly Sensitized Deceased Organ Donor to the Recipients of Each Kidney

Abstract

We report for the first time the adoptive transfer of donor HLA‐specific allosensitization in two recipients following kidney transplantation from a highly sensitized donor. Kidneys from a donation after circulatory death donor were transplanted into two nontransfused, HLA‐specific antibody negative males receiving their first transplant. Antibody screening 7 days after transplant showed high level de novo IgG HLA class I‐ and class II‐specific antibodies in both recipients, with largely overlapping antibody profiles but no antibodies to donor HLA. The unusually rapid appearance of de novo alloantibodies in immunosuppressed nonsensitized recipients and absence of donor HLA‐specific antibody prompted testing of stored donor serum that revealed high antibody levels with specificities very similar to those seen in both recipients, but in addition the presence of strong antibodies to each recipient HLA. Alloantibody levels gradually declined but were still detectable at 3 months. These findings suggest that alloreactive passenger B cells/plasma cells within the kidneys of highly sensitized donors may give rise to rapid development of posttransplant de novo HLA‐specific alloantibodies. While the clinical significance of this phenomenon is uncertain it provides one explanation for the appearance of de novo HLA‐specific antibodies directed against third party but not donor HLA.

Transfer of donor anti-HLA antibody expression to multiple transplant recipients: A potential variant of the passenger lymphocyte syndrome?

“…Several case reports describe a similar situation and timeline, and combined together offer a potential insight regarding the immune cell type responsible . Maxfield et al described 2 nonsensitized renal transplant recipients who developed third‐party anti‐HLA antibodies at 7 days that matched the sensitized donor profile and lasted beyond 3 months . B cells or plasma cells were considered the likely culprits.…”

“…Combined with our own report, these various case series suggest that donor lymphoid tissue originating memory cells (likely plasma cells) enter and remain in the recipient circulation long term. The case report utilizing rituximab, with no circulating B cells and the 2 case reports observing antibodies within a short 7 days from transplant, argue against the theory that B cells are the bridging cell that subsequently differentiates into plasma cells . Additionally, tissue‐resident B cells are associated with local antigens, so they should not be outside the allograft in significant numbers.…”

Memory T‐cell exhaustion and tolerance in transplantation

“…First, due to clonal expansion upon encounter with antigen, the memory pool is much larger than the naive T-cell pool for any given antigen. 62 Since de Leur et al have observed infiltration of host memory T cells into the graft tissue and differentiation into T rm , understanding the impact of lymphodepletion on alloreactive tissue resident memory cells is likely of clinical relevance. However, donor-derived T rm involvement in the failure to achieve long-term tolerance seems less likely according to their study since in host T rm cells dominate in grafts that reject beyond the first year.…”

“…However, it has been observed clinically that if a donor is highly sensitized to the recipient, allospecific responses can be generated post-transplant despite a lack of pre-existing donor-specific antibodies in the recipient during screening. 62 Since de Leur et al have observed infiltration of host memory T cells into the graft tissue and differentiation into T rm , understanding the impact of lymphodepletion on alloreactive tissue resident memory cells is likely of clinical relevance. Because homeostatic proliferation following lymphodepletion gives rise to T cells with a memory phenotype, it is possible that patients receiving lymphodepletion could develop T rm cells at increased frequencies relative to patients who do not undergo lymphodepletion prior to transplant.…”

Human Leukocyte Antigen Sensitization in Solid Organ Transplantation: A Primer on Terminology, Testing, and Clinical Significance for the Apheresis Practitioner

“…Other studies have documented post‐transplant HLA seroconversion in 50–76% of previously transplanted patients . In a single report, HLA‐specific allosensitization was thought to be transferred to the recipient from a highly sensitized organ donor . In individuals without a history of transplantation, depending on whether or not leukoreduced products are used, transfusion can account for 20 to 33% of sensitizing events .…”