Current Approaches to Desensitization in Solid Organ Transplantation

Schinstock, Carrie A.; Tambur, Anat R.; Stegall, Mark D.

doi:10.3389/fimmu.2021.686271

Cited by 17 publications

(13 citation statements)

References 51 publications

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“…Depletion of circulating B cells is one major component of desensitization strategies. The chimeric anti-CD20 monoclonal antibody Rituximab is the most widely-used agent, although several other agents are in development (36,37). Targeted depletion of B cells with agents such as Rituximab has the…”

Section: Targeting B Cells and Plasma Cellsmentioning

confidence: 99%

Donor specific HLA antibody in hematopoietic stem cell transplantation: Implications for donor selection

Krummey

Gareau

2022

Front. Immunol.

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Advances in hematopoietic stem cell transplant (HSCT) have led to changes in the approach to donor selection. Many of these new approaches result in greater HLA loci mismatching, either through the selection of haploidentical donors or permissive HLA mismatches. Although these approaches increase the potential of transplant for many patients by expanding the number of acceptable donor HLA genotypes, they add the potential barrier of donor-specific HLA antibodies (DSA). DSA presents a unique challenge in HSCT, as it can limit engraftment and lead to graft failure. However, transient reduction of HLA antibodies through desensitization treatments can limit the risk of graft failure and facilitate engraftment. Thus, the consideration of DSA in donor selection and the management of DSA prior to transplant are playing an increasingly important role in HSCT. In this review, we will discuss studies addressing the role of HLA antibodies in HSCT, the reported impact of desensitization on DSA levels, and the implications for selecting donors for patients with DSA. We found that there is a clear consensus that moderate strength DSA should be avoided, while desensitization strategies are reported to be effective in most cases at reducing DSA to amenable levels. There is limited information regarding the impact of specific characteristics of DSA, such as HLA loci or overall level of sensitization, which could further aid in donor selection for sensitized HSCT candidates.

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Section: Targeting B Cells and Plasma Cellsmentioning

confidence: 99%

Donor specific HLA antibody in hematopoietic stem cell transplantation: Implications for donor selection

Krummey

Gareau

2022

Front. Immunol.

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“…For example, patients with positive DSA at higher risk of rejection before second or third transplantations could receive personalized therapy. Such desensitization strategies based on plasma exchange, intravenous immunoglobulin infusion, anti-CD20 or anti CD38 monoclonal antibodies, proteasome inhibitors, complement inhibitors, or interleukin-6 blockers are used in SOT (Schinstock et al 2021). Additionally, DSA may be the cause of rapid graft decompensation and the relatively poor response to treatment in many cases.…”

Section: Impact Of Dsa Detection On Treatment Strategiesmentioning

confidence: 99%

Immunology and Donor-Specific Antibodies in Corneal Transplantation

Major¹,

Foroncewicz

Szaflik

et al. 2021

Arch. Immunol. Ther. Exp.

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The first human corneal transplantation was performed in 1905 by Eduard Zirm in the Olomouc Eye Clinic, now Czech Republic. However, despite great advancements in microsurgical eye procedures, penetrating keratoplasty in high-risk patients (e.g., vascularized or inflamed corneal tissue, consecutive transplants) remains a challenge. The difficulty is mainly due to the risk of irreversible allograft rejection, as an ocular immune privilege in these patients is abolished and graft rejection is the main cause of corneal graft failure. Therefore, tailored immunosuppressive treatment based on immunological monitoring [e.g., donor-specific antibodies (DSA)] is considered one of the best strategies to prevent rejection in transplant recipients. Although there is indirect evidence on the mechanisms underlying antibody-mediated rejection, the impact of DSA on cornea transplantation remains unknown. Determining the role of pre-existing and/or de novo DSA could advance our understanding of corneal graft rejection mechanisms. This may help stratify the immunological risk of rejection, ultimately leading to personalized treatment for this group of transplant recipients.

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“…The elevated risk of antibody‐mediated rejection (ABMR) (30%–40%) in these early‐era DSA‐positive transplants highlights the overall greater immunologic risk of recipients of incompatible transplants 10–12 . Several novel desensitization strategies have since then been evaluated with promising results 13–15 . Our group has shown that a multi‐drug approach to desensitization leads to durable desensitization and prevents compensatory humoral mechanisms.…”

Section: Introductionmentioning

confidence: 99%

“…[10][11][12] Several novel desensitization strategies have since then been evaluated with promising results. [13][14][15] Our group has shown that a multi-drug approach to desensitization leads to durable desensitization and prevents compensatory humoral mechanisms. The combination of proteasome inhibition (carfilzomib [CFZ]), which targets plasma cells (PCs), and costimulation blockade, which disrupts germinal centers and T follicular helper (Tfh) cells interaction with naïve B cells, allows for prolonged graft survival in a stringent skin-sensitized nonhuman primate model, thus demonstrating the utility of dual-targeting strategies.…”

Section: Introductionmentioning

confidence: 99%