Clinical Relevance of Pretransplant Donor-Directed Antibodies Detected by Single Antigen Beads in Highly Sensitized Renal Transplant Patients

Berg‐Loonen, Ella M. van den; Billen, Evy V.A.; Voorter, Christina E.M.; Heurn, L. W. Ernest van; Claas, Frans H.J.; Hooff, J. P. van; Christiaans, Maarten H. L.

doi:10.1097/tp.0b013e31816b3ed1

Cited by 130 publications

(93 citation statements)

References 4 publications

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“…Categorization of deceased donor kidney transplant recipients at risk for early graft failure was not based on Luminex-detected DSA since several reports indicate that donor-specific HLA antibodies detected exclusively by the highly sensitive Luminex technology are not necessarily associated with graft rejection [30][31][32]. In addition, definition of unacceptable HLA antigens by Luminex technology may put the deceased donor kidney transplant candidate at a disadvantage due to prolonged waiting time.…”

Section: Identification Of High-risk Sensitized Patientsmentioning

confidence: 98%

Kidney transplantation in highly sensitized patients: are there options to overcome a positive crossmatch?

Morath

Schmidt

Opelz

et al. 2011

Langenbecks Arch Surg

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Presensitization against a broad array of human leukocyte antigens (HLA) is associated with prolonged waiting times and inferior graft survival in kidney transplantation. Since the late 1960s, a positive lymphocytotoxic crossmatch has been considered a contraindication for kidney transplantation and solutions, such as enrollment of eligible patients in the Acceptable Mismatch Program of Eurotransplant and kidney paired donation in the case of living donor kidney transplantation, have been proposed to avoid this barrier. Alternatively, a positive crossmatch might not be considered as a contraindication for kidney transplantation and one can try to overcome this hurdle by desensitization. In principle, there are three different ways to overcome the crossmatch barrier by desensitization. The highly sensitized patient awaiting a cadaveric kidney transplant may be desensitized either immediately pretransplant when an organ is offered or in advance, during the time on the waiting list, to increase his chance of having a negative crossmatch at the time of transplantation. In the case of living donor kidney transplantation, the patient can be desensitized for days to weeks until the positive crossmatch with his intended living kidney donor becomes negative. "Heidelberg algorithm" is a combination of different measures, such as pretransplant risk estimation, good HLA match, inclusion of patients in the Eurotransplant Acceptable Mismatch program, and desensitization, which leads to timely transplantation and excellent survival rates in highly sensitized patients at a low rate of toxicity. We believe that all available options should be utilized in an integrated manner for the transplantation of kidney transplant recipients who are at a high risk of antibody-mediated rejection.

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Section: Identification Of High-risk Sensitized Patientsmentioning

confidence: 98%

Kidney transplantation in highly sensitized patients: are there options to overcome a positive crossmatch?

Morath

Schmidt

Opelz

et al. 2011

Langenbecks Arch Surg

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show abstract

“…The major advantage of Luminex technology in anti-HLA antibody detection, especially using SA analysis, is the accurate evaluation of complex sera from highly immunized patients for whom it is very difficult to identify antibody specificity and, therefore, find a compatible donor [23,24]. Each anti-HLA antibody may bind multiple epitopes, structurally defined by few amino-acid residues common to several class I and II HLA molecules [25].…”

Section: Recent Advantages In Anti-hla Antibody Detection By Luminexmentioning

confidence: 99%

Luminex and antibody detection in kidney transplantation

2012

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Preformed anti-human leukocyte antigen (HLA) antibodies have a negative effect on kidney transplantation outcome with an increased rejection rate and reduction in survival. Posttransplantation production of donor-specific anti-HLA antibodies is indicative of an active immune response and risk of transplantation rejection. For many years the primary technique for anti-HLA antibody detection was complement-dependent cytotoxicity (CDC), which has been integrated by solid-phase assays as HLA antigen-coated bead methods (Luminex). This new technological approach has allowed identification of anti-HLA antibodies, not detectable using conventional CDC method, in patients awaiting kidney transplantation. Moreover, use of Luminex technology has enabled better definition of acceptable or unacceptable antigens favoring transplantation in highly immunized patients. However, there are still many unresolved issues, including the clinical relevance of antibodies detected with this system.

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“…A mérés transzplantáció előtti szé-rumból, Luminex SAB IgG-teszttel történt, a páciensek mindegyike negatív eredményt mutatott a CDC és ELI-SA screening tesztekben [36]. A fenti tanulmányok mellett más szerzők megfi gyelései is kétségbe vonják a kizá-rólag SAB-technikával detektálható HLA-alloantitestek klinikai jelentőségét, ezért feltételezhetően az ELISA és CDC screenin g tesztben negatív páciensek esetén az SAB-technológiával a transzplantációt megelőzően meghatározott antitestek klinikai jelentősége korlátozott, még ha ezek speciálisan a do nor ellen irányulnak is [37]. Ezért nem ajánlott azon antigének UAM-ként történő megjelölése, amelyeket csak az SAB-teszttel lehet kimutatni.…”

Section: A Luminex Sab-teszt Során Detektált Antitestek Jelentőségeunclassified

“…A Luminex SAB-teszt széles körűen elfogadott a DSA-k kimutatására, holott még mindig nem tisztázott azon antitestek klinikai jelentősége, amelyek csak a hiperszenzitív Luminex SAB-módszerrel mutathatók ki [37]. A tesztet ért kritikák annak technikai hiányosságaira hív-ják fel a fi gyelmet.…”

Section: Technikai Ajánlásokunclassified

Challenges of the modern antibody diagnostics in kidney transplantation

Wettstein

Szentiványi

2014

Orvosi Hetilap

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A transzplantációs immunológia kiemelt fontosságú területe az antitestmediált rejectio elleni küzdelem, amelynek hátterében a graft által prezentált humán leukocytaantigének ellen képződő antitestek állnak. A szilárd fázisú immunológiai tesztek bevezetésével jelentősen megváltozott az antitestek monitorozásának gyakorlata, aminek jelentősége van a transzplantációt megelőzően és azt követően is. Ennek ellenére hiányosak az ismeretek a teszt során detektált antitestek klinikai relevanciáját tekintve, ezenfelül technikai kihívások és a betegellátás során alkalmazott különböző stratégiák színesítik a képet. A szerzők a transzplantációs antitestmonitorozás laboratóriumi módszereinek egységesí-tésére vonatkozó ajánlásokat és a vesetranszplantált betegek ellátásában javasolt algoritmusokat mutatják be összefog-laló közleményükben. A szilárd fázisú technikák kombinálása a komplementaktiváció kimutatásával ígéretes eszköz-nek mutatkozik. A komplementkötő antitestek kimutatásán alapuló módszerek fontos kérdésekre adhatnak választ a detektált antitestek klinikai relevanciáját illetően. Az új módszerek alkalmazása során felmerülő kérdések megválaszo-lása és az ajánlások ismerete szükséges ahhoz, hogy ezen a dinamikusan fejlődő területen naprakészek maradjunk. Orv. Hetil., 2014, 155(46), 1820-1830. Kulcsszavak: antitestmediált rejectio, HLA-antitestek, vesetranszplantáció Challenges of the modern antibody diagnostics in kidney transplantationOvercoming antibody mediated rejection is of increasing interest in the fi eld of transplantation immunology. The recipient's antibodies against the graft human leukocyte antigens are responsible for antibody mediated graft injury. Introduction of the solid phase immunoassay technology radically changed the monitoring practice of antibodies against human leukocyte antigens, and this has consequences both for pretransplant and posttransplant phases, though our knowledge about the clinical interpretation of the detected antibodies is limited. This integrating review reports recommendations and algorithms regarding the management of kidney transplant patients. The detection of complement activation combined with the solid phase techniques is a promising new approach in antibody testing. The C4d and especially the more sensitive C1q methods have the potential to answer pivotal questions about the clinical relevance of antibodies. Answering the questions that the applied new methods raised and reviewing the recommendations are needed to remain up to date with this dynamically developing fi eld.

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Clinical Relevance of Pretransplant Donor-Directed Antibodies Detected by Single Antigen Beads in Highly Sensitized Renal Transplant Patients

Cited by 130 publications

References 4 publications

Kidney transplantation in highly sensitized patients: are there options to overcome a positive crossmatch?

Kidney transplantation in highly sensitized patients: are there options to overcome a positive crossmatch?

Luminex and antibody detection in kidney transplantation

Challenges of the modern antibody diagnostics in kidney transplantation

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