(F)Utility of the physical crossmatch for living donor evaluations in the age of the virtual crossmatch

Sullivan, Harold C.; Dean, Christina L.; Liwski, Robert; Biswas, Shilpee; Goodman, Abigail; Krummey, Scott M.; Gebel, Howard M.; Bray, Robert A.

doi:10.1016/j.humimm.2018.08.001

Cited by 19 publications

(17 citation statements)

References 31 publications

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“…The remaining candidates were not transplanted for other reasons. Additional studies also report transplanting across this type of discordant result with no deleterious outcomes associated . Collectively, the clinical findings support the contention that such positive FCXMs were due to a non‐HLA antibody and should not be considered a contraindication for transplantation …”

Section: Complex Scenariossupporting

confidence: 58%

“…Additional studies also report transplanting across this type of discordant result with no deleterious outcomes associated. 46 Collectively, the clinical findings support the contention that such positive FCXMs were due to a non-HLA antibody and should not be considered a contraindication for transplantation. [47][48][49] Moreover, false positive B-cell FCXMs can occur when immunoglobulins or immune complexes bind Fc or complement receptors on B cells.…”

Section: Future Of Crossmatchingmentioning

confidence: 56%

“…Reports of this particular scenario in which the FCXM is positive in the absence of donor‐specific HLA antibody occur with significant frequency. In work published by Sullivan et al, the rate for this discordant result, among living donors, was reported to be 20% (20 out of 100 cases reviewed). The majority (90%) of the positive FCXMs were B‐cell only and were moderate to weak in strength.…”

Section: Complex Scenariosmentioning

confidence: 96%

“…Several different factors must be considered when interpreting these cases: (a) Recent evidence suggests that a proportion of VXM +/FCXM− cases are likely the result of weak anti-HLA antibody that cannot elicit a positive FCXM. 46 Sullivan et al showed that this scenario represented~5% (5/100) of cases, and, based on the FlowPRA screening assay, the positive VXM was the result of true, albeit weak, anti-HLA antibody. (b) The quality of donor material used in the crossmatch can greatly affect the outcome of the crossmatch.…”

Section: Scenario 4: Fcxm Negative/vxm Positivementioning

confidence: 99%

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Out with the old, in with the new: Virtual versus physical crossmatching in the modern era

Morris

Sullivan

Krummey

et al. 2019

HLA

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The virtual crossmatch (VXM) is gaining acceptance as an alternative approach to assess donor:recipient compatibility prior to transplantation. In contrast to a physical crossmatch, the virtual crossmatch does not require viable donor cells but rather relies on complete HLA typing of the donor and current antibody assessment of the recipient. Thus, the VXM can be performed in minutes which allows for faster transplant decisions thereby increasing the likelihood that organs can be shipped across significant distances yet safely transplanted. Here, we present a brief review of the past 50 years of histocompatibility testing; from the original complement‐dependent cytotoxicity crossmatch in 1969 to the new era of molecular HLA typing, solid‐phase antibody testing and virtual crossmatching. These advancements have shaped a paradigm shift in our approach to transplantation. That is, foregoing a prospective physical crossmatch in favor of a VXM. In this review, we undertake an in‐depth analysis of the pros‐ and cons‐ of physical and virtual crossmatching.Finally, we provide objective data on the selected use of the VXM which demonstrate the value of a VXM in lieu of the traditional physical crossmatch for safe and efficient organ transplantation.

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Section: Complex Scenariossupporting

confidence: 58%

Section: Future Of Crossmatchingmentioning

confidence: 56%

Section: Complex Scenariosmentioning

confidence: 96%

Section: Scenario 4: Fcxm Negative/vxm Positivementioning

confidence: 99%

See 2 more Smart Citations

Out with the old, in with the new: Virtual versus physical crossmatching in the modern era

Morris

Sullivan

Krummey

et al. 2019

HLA

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“…The B cell FCXM has been associated with a high false positive rate, with studies demonstrating the superiority of the SAB or virtual crossmatch over B cell FCXM for detecting class II DSA [36][37][38]. However, the relative homogenous nature of our immunotherapy does enable equitable comparison of risk posed by RMM and preformed DSA, which is important.…”

mentioning

confidence: 99%

Donor-specific antibodies detected by single antigen beads alone can help risk stratify patients undergoing retransplantation across a repeat HLA mismatch

Lucisano

Thiruvengadam

Hassan

et al. 2020

American Journal of Transplantation

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Whether reexposure to mismatched HLA antigens (RMM) in the setting of a negative crossmatch is associated with increased immunological risk remains an area of uncertainty. This is due to evidence derived predominantly from registry data, which lacks comprehensive information on alloantibody and rejection. In this study, we analyze the impact of low‐level preformed donor‐specific antibodies (DSA) against an RMM on transplant outcomes. From 1988 consecutive renal transplant recipients, we analyzed 179 patients undergoing retransplantation, of whom 55 had a RMM. All patients were crossmatch negative and preformed DSA were detected by single antigen beads alone. Multivariate analysis revealed that patients with preformed DSA against an RMM were independently at risk of antibody‐mediated rejection (HR 8.70 [3.42‐22.10], P < .0001) and death‐censored allograft loss (HR 3.08 [1.17‐8.14], P = .023). In addition, prior transplant nephrectomy (HR 2.04 [1.00‐4.17], P = .0495) was also associated with allograft failure, whereas receiving a retransplant that was matched at HLA class II was associated with a favorable outcome (HR 0.37 [0.14‐0.99], P = .047). In the absence of preformed DSA, an RMM was not associated with de novo DSA development, rejection, or allograft loss. In conclusion, an RMM portends increased immunological risk only in the presence of a preformed DSA in patients undergoing retransplantation.

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Human Leukocyte Antigens

Sullivan¹,

Alquist²

2022

Practical Transfusion Medicine

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Immune tolerance is a known immune cascade of events by which our immune system can regulate its function, avoiding unwanted immune response reactions to immune privilege sites in our body. The role of HLA-G in fetal-maternal immune tolerance to prevent the embryo from being rejected can be applied to the process of transplantation as well as other clinical applications. The gut is also an important site of immune tolerance, with the constant assault of food antigens and its billions of resident microbes. In transplantation, the level of expression of HLA-G in the graft tissues correlates with organ acceptance and controls the recipient's immune response. Furthermore, tumor immune escape is associated with both the expression of immune checkpoint molecules on peripheral immune cells and soluble forms of the human leukocyte antigen-G (HLA-G) in the blood, which is consequently discussed as a clinical biomarker for disease status and outcome of cancer patients. Future studies are needed to explore more immune tolerance pathways for HLA-G and to apply and use this in transplantation to prevent rejection and treat miscarriage cases and autoimmune diseases. In addition, therapies to block HLA-G in malignant diseases are exciting and need more clinical trials. This chapter addresses and reviews the published articles related to the advances in HLA G and immune tolerance.

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(F)Utility of the physical crossmatch for living donor evaluations in the age of the virtual crossmatch

Cited by 19 publications

References 31 publications

Out with the old, in with the new: Virtual versus physical crossmatching in the modern era

Out with the old, in with the new: Virtual versus physical crossmatching in the modern era

Donor-specific antibodies detected by single antigen beads alone can help risk stratify patients undergoing retransplantation across a repeat HLA mismatch

Human Leukocyte Antigens

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