Organtransplantation – Welche spenderspezifischen HLA-Antikörper sind akzeptabel?

HLA-Merkmale, gegen die Patienten auf der Transplantationswarteliste immunisiert sind, können als nicht-akzeptable HLA-Antigendifferenzen (NAHA) definiert werden. Bei breit immunisierten Patienten kann es schwierig sein, alle HLA-Antikörper als NAHA zu berücksichtigen, da dies die Zahl kompatibler Spender minimiert. Dieser Beitrag gibt eine Übersicht, welche Kriterien bei der Auswahl der Antikörper für die Definition von NAHA hilfreich sein können.

Abstract

Preformed HLA antibodies are associated with an increased risk for rejections and decreased graft survival in solid organ transplantation. If such antibodies are detected, the corresponding antigens can be defined as unacceptable antigens in most transplant programs. This prohibits allocation of transplants expressing any of these unacceptable antigens. As assignment of unacceptable HLA antigens reduces the number of potential donors, considering all HLA antibodies might be difficult in highly immunized patients. This review focuses mainly on kidney transplantation and provides an overview about strategies to choose the optimal transplant program for highly immunized patients and possible criteria for selection of HLA antibodies in the assignment of unacceptable antigens.

Schlüsselwörter

HLA-Antikörper - nicht-akzeptable HLA-Antigendifferenzen (NAHA) - Organtransplantation - antikörpervermittelte Abstoßung - Transplantatüberleben

Key words

HLA antibodies - unacceptable HLA antigens - solid organ transplantation - antibody mediated rejection - graft survival

Publication History

Article published online:
30 November 2023

• Literatur

• 1 Tambur AR, Bestard O, Campbell P. et al. Sensitization in transplantation: Assessment of Risk 2022 Working Group Meeting Report. Am J Transplant 2023; 23: 133-149
• 2 Ziemann M, Heßler N, König IR. et al. Unacceptable human leucocyte antigens for organ offers in the era of organ shortage: influence on waiting time before kidney transplantation. Nephrol Dial Transplant 2017; 32: 880-889
• 3 de Ferrante H, Smeulders B, Tieken I. et al. Immunized patients face reduced access to transplantation in the Eurotransplant kidney allocation system. Transplantation. 2023 107: 2247–54
• 4 Ziemann M, Suwelack B, Banas B. et al. Determination of unacceptable HLA antigen mismatches in kidney transplant recipients. HLA. 2022; 100: 3–17
• 5 Aubert O, Bories M-C, Suberbielle C. et al. Risk of antibody-mediated rejection in kidney transplant recipients with anti-HLA-C donor-specific antibodies. Am J Transplant 2014; 14: 1439-1445
• 6 Bachelet T, Martinez C, Del Bello A. et al. Deleterious impact of donor-specific anti-hla antibodies toward HLA-Cw and HLA-DP in kidney transplantation. Transplantation 2016; 100: 159-166
• 7 Cunha APL, Fabreti-Oliveira RA, Lasmar MF. et al. Clinical Outcome of Kidney Transplant Patients on the Allograft Function, Loss, Effects of HLA-DQB1-DSA+, and Graft Survival. Transplant Proc 2021; 53: 2188-2196
• 8 Frischknecht L, Deng Y, Wehmeier C. et al. Swiss Transplant Cohort Study: The impact of pre-transplant donor specific antibodies on the outcome of kidney transplantation - Data from the Swiss transplant cohort study. Front Immunol. 2022. 13. 1005790
• 9 Park BG, Park Y, Joo DJ. et al. Clinical significance of donor-specific anti-HLA-DR51/52/53 antibodies for antibody-mediated rejection in kidney transplant recipients. Korean J Transplant 2019; 33: 47-54
• 10 Zecher D, Bach C, Staudner C. et al. Characteristics of donor-specific anti-HLA antibodies and outcome in renal transplant patients treated with a standardized induction regimen. Nephrol Dial Transplant 2017; 32: 730-737
• 11 Kamburova EG, Wisse BW, Joosten I. et al. Differential effects of donor-specific HLA antibodies in living versus deceased donor transplant. Am J Transplant. 2018 18: 2274–84
• 12 Ziemann M, Altermann W, Angert K. et al. Preformed donor-specific hla antibodies in living and deceased donor transplantation: a multicenter study. Clin J Am Soc Nephrol 2019; 14: 1056-1066
• 13 Wehmeier C, Hönger G, Schaub S. Caveats of HLA antibody detection by solid-phase assays. Transplant Int 2020; 33: 18-29
• 14 Lefaucheur C, Loupy A, Hill GS. et al. Preexisting donor-specific HLA antibodies predict outcome in kidney transplantation. J Am Soc Nephrol 2010; 21: 1398-1406
• 15 Hönger G, Amico P, Arnold M-L. et al. Effects of weak/non-komplement-binding HLA antibodies on C1q-binding. HLA 2017; 90: 88-94
• 16 Patel R, Terasaki PI. Significance of the positive crossmatch test in kidney transplantation. N Engl J Med 1969; 280: 735-739
• 17 Opelz G, Döhler B, Süsal C. Analysis of positive kidney, heart, and liver transplant crossmatches reported to the Collaborative Transplant Study. Hum Immunol 2009; 70: 627-630
• 18 British Society for Histocompatibility & Immunogenetics, British Transplantation Society: BSHI & BTS Guideline. The detection and characterisation of clinically relevant antibodies in allotransplantation. 2015 verfügbar unter https://bts.org.uk/wp-content/uploads/2016/09/06_BTS_BSHI_Antibodies-1.pdf (10. Oktober 2023)
• 19 Couzi L, Araujo C, Guidicelli G. et al. Interpretation of positive flow cytometric crossmatch in the era of the single-antigen bead assay. Transplantation 2011; 91: 527-35
• 20 Meneghini M, Melilli E, Martorell J. et al. Combining sensitive crossmatch assays with donor/recipient human leukocyte antigen eplet matching predicts living-donor kidney Transplant Outcome. Kidney Int Rep 2018; 3: 926-938
• 21 Osickova K, Hruba P, Kabrtova K. et al. Predictive potential of flow cytometry crossmatching in deceased donor kidney transplant recipients subjected to peritransplant desensitization. Front Med (Lausanne) 2021; 8: 780636
• 22 Kwon H, Kim YH, Kim JY. et al. The results of HLA-incompatible kidney transplantation according to pre-transplant crossmatch tests: Donor-specific antibody as a prominent predictor of acute rejection. Clin Transplant 2019; 33: e13533
• 23 Mumford L, Fuggle SV, Martorell J. et al. A Europe wide acceptable mismatch program will enable transplantation of long waiting highly sensitised patients with a compatible donor. Transplant Immunol 2021; 64: 101354