Back to the future: application of contemporary technology to long-standing questions about the clinical relevance of human leukocyte antigen-specific alloantibodies in renal transplantation

Taylor, Craig; Kosmoliaptsis, Vasilis; Summers, Dominic M.; Bradley, J. Andrew

doi:10.1016/j.humimm.2009.05.001

Cited by 67 publications

(59 citation statements)

References 43 publications

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“…As shown in Figure 8, the antibodies against A2, A69, B51, and B52 exhibited oversaturation that disappeared upon the dilution of the serum. This prozoning effect has been reported by others with the SA Luminex bead assay [119][120][121][122][123] . Dilution of the serum to exclude the oversaturation of antibodies is critical when the antibody analysis is performed on the sera of highly sensitized TCs who have been subjected to immunomodulation/desensitization.…”

Section: Bead Oversaturationsupporting

confidence: 81%

Methodological aspects of anti-human leukocyte antigen antibody analysis in solid organ transplantation

Lobashevsky¹

2014

WJT

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Donor human leukocyte antigen (HLA)-specific antibodies (DSA) play an important role in solid organ transplantation. Preexisting IgG isotype DSA are considered a risk factor for antibody mediated rejection, graft failure or graft loss. The post-transplant development of DSA depends on multiple factors including immunogenicity of mismatched antigens, HLA class Ⅱ typing of the recipient, cytokine gene polymorphisms, and cellular immunoregulatory mechanisms. De novo developed antibodies require special attention because not all DSA have equal clinical significance. Therefore, it is important for transplant clinicians and transplant immunologists to accurately characterize DSA. In this review, the contemporary immunological techniques for detection and characterization of anti-HLA antibodies and their pitfalls are described.

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Section: Bead Oversaturationsupporting

confidence: 81%

Methodological aspects of anti-human leukocyte antigen antibody analysis in solid organ transplantation

Lobashevsky¹

2014

WJT

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“…This fact may contribute to the controversy on the clinical relevance of HLAab as there is an eminent discrepancy in antigen density between the antibody detection assay and the surface of endothelial cells as the antibody target of a renal allograft. Consequently, HLA-DQ antibodies detected exclusively by SAB reveal only a low immunological risk for renal transplant [21]. Disparities in relative antigen quantity exist not only across different bead formats but also among SAB.…”

Section: Principles Of the Luminex Methodsmentioning

confidence: 99%

Luminex® and Its Applications for Solid Organ Transplantation, Hematopoietic Stem Cell Transplantation, and Transfusion<sup>*</sup>

Lachmann

Todorova

Schulze

et al. 2013

Transfus Med Hemother

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The detection of antibodies against the human leukocyte antigen (HLA) complex has become indispensable in every clinical practice. The development of solid-phase assays like the Luminex allows the standardized measurement of anti-HLA antibodies (HLAab) with high sensitivity, albeit the relevance for some clinical settings remains a matter of debate. In this review we aim to describe the principle of Luminex-based antibody detection, including two modifications that allow identifying solely complement-activating antibodies. We then describe three applications for Luminex: i) detection of HLAab preceding solid-organ transplantation and monitoring of donor-specific antibodies posttransplant as a risk factor for antibody-mediated rejection; ii) presence of HLAab in recipients as a risk for graft failure in hematopoietic stem cell transplantation, especially in haploidentical or mismatched transplantations; iii) role of HLAab in blood transfusion including refractory thrombocytopenia and selection of suitable platelet donors, transfusion-related lung injury after plasma transfusion, and immunization against HLA after red blood cell transfusion despite leukodepletion. Although the Luminex platform constitutes a potent technology for HLA antibody detection, some drawbacks require the well-educated analysis and interpretation of data in critical cases. In addition, Luminex has become an important tool to identify clinically relevant antibodies.

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“…Pretransplant antibody screening was performed using a dithiothreitol (DTT)-modified complement-dependent cytotoxicity (CDC) assay, as described previously (10). Antibody characterization was undertaken using HLA class I and class II single-antigen HLA-specific antibody detection beads (LABScreen R ; One Lambda Inc., Canoga Park, CA, USA).…”

Section: Casementioning

confidence: 99%

Preformed Donor HLA-DP-Specific Antibodies Mediate Acute and Chronic Antibody-Mediated Rejection Following Renal Transplantation

Jolly

Key

Rasheed

et al. 2012

American Journal of Transplantation

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Donor-specific HLA alloantibodies may cause acute and chronic antibody-mediated rejection (AMR) and significantly compromise allograft survival. The clinical relevance of antibodies directed against some HLA class II antigens, particularly HLA-DP, is less clear with conflicting reports on their pathogenicity. We report two patients with high levels of pretransplant donorspecific HLA-DP antibodies who subsequently developed recurrent acute AMR and graft failure. In both cases, there were no other donor-specific HLA alloantibodies, suggesting that the HLA-DP-specific antibodies may be directly pathogenic.

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Back to the future: application of contemporary technology to long-standing questions about the clinical relevance of human leukocyte antigen-specific alloantibodies in renal transplantation

Cited by 67 publications

References 43 publications

Methodological aspects of anti-human leukocyte antigen antibody analysis in solid organ transplantation

Methodological aspects of anti-human leukocyte antigen antibody analysis in solid organ transplantation

Luminex® and Its Applications for Solid Organ Transplantation, Hematopoietic Stem Cell Transplantation, and Transfusion<sup>*</sup>

Preformed Donor HLA-DP-Specific Antibodies Mediate Acute and Chronic Antibody-Mediated Rejection Following Renal Transplantation

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