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 egységesítésére vonatkozó ajánlásokat és a vesetranszplantált betegek ellátásában javasolt algoritmusokat mutatják be összefoglaló közleményükben. A szilárd fázisú technikák kombinálása a komplementaktiváció kimutatásával ígéretes eszköznek mutatkozik. A komplementkötő antitestek kimutatásán alapuló módszerek fontos kérdésekre adhatnak választ a detektált antitestek klinikai relevanciáját illetően. Az új módszerek alkalmazása során felmerülő kérdések megválaszolása és az ajánlások ismerete szükséges ahhoz, hogy ezen a dinamikusan fejlődő területen naprakészek maradjunk. Orv. Hetil., 2014, 155(46), 1820–1830.
Süsal, C., Roelen, D. L., Fischer, G., et al.: Algorithms for the determination of unacceptable HLA antigen mismatches in kidney transplant recipients. Tissue Antigens, 2013, 82(2), 83–92.
Tait, B. D., Süsal, C., Gebel, H. M., et al.: Consensus guidelines on the testing and clinical management issues associated with HLA and non-HLA antibodies in transplantation. Transplantation, 2013, 95(1), 19–47.
Halloran, P. F., Wadgymar, A., Ritchie, S., et al.: The significance of the anti-class I antibody response. I. Clinical and pathologic features of anti-class I-mediated rejection. Transplantation, 1990, 49(1), 85–91.
Halloran, P. F., Schlaut, J., Solez, K., et al.: The significance of the anti-class I antibody response. II. Clinical and pathologic features of renal transplants with anti-class I-like antibody. Transplantation, 1992, 53(3), 550–555.
Regele, H., Exner, M., Watschinger, B., et al.: Endothelial C4d deposition is associated with inferior kidney allograft outcome independently of cellular rejection. Nephrol. Dial. Transplant., 2001, 16(10), 2058–2066.
Feucht, H. E., Schneeberger, H., Hillebrand, G., et al.: Capillary deposition of C4d complement fragment and early renal graft loss. Kidney Int., 1993, 43(6), 1333–1338.
Feucht, H. E., Felber, E., Gokel, M. J., et al.: Vascular deposition of complement-split products in kidney allografts with cell-mediated rejection. Clin. Exp. Immunol., 1991, 86(3), 464–470.
Racusen, L. C., Haas, M.: Antibody-mediated rejection in renal allografts: lessons from pathology. Clin. J. Am. Soc. Nephrol., 2006, 1(3), 415–420.
Crespo, M., Pascual, M., Tolkoff-Rubin, N., et al.: I. Acute humoral rejection in renal allograft recipients: Incidence, serology, and clinical characteristics. Transplantation, 2001, 71(5), 652–658.
Einecke, G., Sis, B., Reeve, J., et al.: Antibody-mediated microcirculation injury is the major cause of late kidney transplant failure. Am. J. Transplant., 2009, 9(11), 2520–2531.
Wiebe, C., Gibson, I. W., Blydt-Hansen, T. D., et al.: Evolution and clinical pathologic correlations of de novo donor-specific HLA antibody post kidney transplant. Am. J. Transplant., 2012, 12(5), 1157–1167.
Cai, J., Terasaki, P. I.: Human leukocyte antigen antibodies for monitoring transplant patients. Surg. Today, 2005, 35(8), 605–612.
Cai, J., Terasaki, P. I.: Humoral theory of transplantation: mechanism, prevention, and treatment. Hum. Immunol., 2005, 66(4), 334–342.
Everly, M. J., Rebellato, L. M., Haisch, C. E., et al.: Incidence and impact of de novo donor-specific alloantibody in primary renal allografts. Transplantation, 2013, 95(3), 410–417.
Lachmann, N., Terasaki, P. I., Budde, K., et al.: Anti-human leukocyte antigen and donor-specific antibodies detected by luminex posttransplant serve as biomarkers for chronic rejection of renal allografts. Transplantation, 2009, 87(10), 1505–1513.
Hansen, R., Seifeldin, R., Noe, L.: Medication adherence in chronic disease: issues in posttransplant immunosuppression. Transplant. Proc., 2007, 39(5), 1287–1300.
Opelz, G., Döhler, B.: Effect on kidney graft survival of reducing or discontinuing maintenance immunosuppression after the first year posttransplant. Transplantation, 2008, 86(3), 371–376.
2009 Annual Report of the U.S. Organ Procurement and Transplantation Network and the Scientific Registry of Transplant Recipients: Transplant Data 1999–2008. http://www.ustransplant.org/annual_reports/current/
Fuggle, S. V., Martin, S.: Tools for human leukocyte antigen antibody detection and their application to transplanting sensitized patients. Transplantation, 2008, 86(3), 384–390.
Eurotransplant International Foundation Annual Report 2010. Arie Oosterlee and Axel Rahmel. Central Office. Leiden, http://www.eurotransplant.org/cms/index.php?page=annual_reports
Cosio, F. G., Alamir, A., Yim, S., et al.: Patient survival after renal transplantation: I. The impact of dialysis pre-transplant. Kidney Int., 1998, 53(3), 767–772.
Remport, A., Keszei, A., Vamos, E. P., et al.: Association of pre-transplant dialysis duration with outcome in kidney transplant recipients: a prevalent cohort study. Int. Urol. Nephrol,. 2011, 43(1), 215–224.
Opelz, G., Collaborative Transplant Study: Non-HLA transplantation immunity revealed by lymphocytotoxic antibodies. Lancet, 2005, 365(9470), 1570–1576.
Morath, C., Opelz, G., Zeier, M., et al.: Prevention of antibody-mediated kidney transplant rejection. Transpl. Int., 2012, 25(6), 633–645.
Collaborative Transplant Study http://www.ctstransplant.org.
Süsal, C., Döhler, B., Opelz, G.: Presensitized kidney graft recipients with HLA class I and II antibodies are at increased risk for graft failure: a Collaborative Transplant Study report. Hum. Immunol., 2009, 70(8), 569–573.
Doxiadis, I. I., Smits, J. M., Persijn, G. G., et al.: It takes six to boogie: allocating cadaver kidneys in Eurotransplant. Transplantation, 2004, 77(4), 615–617.
De Meester, J., Doxiadis, I. I., Persijn, G. G., et al.: Renal transplantation of highly sensitised patients via prioritised renal allocation programs. Shorter waiting time and above-average graft survival. Nephron, 2002, 92(1), 111–119.
Claas, F. H., Witvliet, M. D., Duquesnoy, R. J., et al.: The acceptable mismatch program as a fast tool for highly sensitized patients awaiting a cadaveric kidney transplantation: short waiting time and excellent graft outcome. Transplantation, 2004, 78(2), 190–193.
Morath, C., Opelz, G., Zeier, M., et al.: Kidney transplantation for high-risk sensitized patients – the „Heidelberg algorithm”. Transplant. Proc., 2011, 43(3), 801–804.
Wahrmann, M., Haidinger, M., Körmöczi, G. F., et al.: Effect of the proteasome inhibitor bortezomib on humoral immunity in two presensitized renal transplant candidates. Transplantation, 2010, 89(11), 1385–1390.
Montgomery, R. A., Lonze, B. E., King, K. E., et al.: Desensitization in HLA-incompatible kidney recipients and survival. N. Engl. J. Med., 2011, 365(4), 318–326.
Patel, R., Terasaki, P. I.: Significance of the positive crossmatch test in kidney transplantation. N. Engl. J. Med., 1969, 280(14), 735–739.
Gombos, P., Opelz, G., Scherer, S., et al.: Influence of test technique on sensitization status of patients on the kidney transplant waiting list. Am. J. Transplant., 2013, 13(8), 2075–2082.
Gupta, A., Iveson, V., Varagunam, M., et al.: Pretransplant donor-specific antibodies in cytotoxic negative crossmatch kidney transplants: are they relevant? Transplantation, 2008, 85(8), 1200–1204.
Süsal, C., Ovens, J., Mahmoud, K., et al.: No association of kidney graft loss with human leukocyte antigen antibodies detected exclusively by sensitive Luminex single-antigen testing: a Collaborative Transplant Study report. Transplantation, 2011, 91(8), 883–887.
Van den Berg-Loonen, E. M., Billen, E. V., Voorter, C. E., et al.: Clinical relevance of pretransplant donor-directed antibodies detected by single antigen beads in highly sensitized renal transplant patients. Transplantation, 2008, 85(8), 1086–1090.
Wolfe, R. A., Ashby, V. B., Milford, E. L., et al.: Comparison of mortality in all patients on dialysis, patients on dialysis awaiting transplantation, and recipients of a first cadaveric transplant. N. Engl. J. Med., 1999, 341(23), 1725–1730.
Zachary, A. A., Montgomery, R. A., Leffell, M. S.: Defining unacceptable HLA antigens. Curr. Opin. Organ. Transplant., 2008, 13(4), 405–410.
Tillou, X., Poirier, N., Le Bas-Bernardet, S., et al.: Recombinant human C1-inhibitor prevents acute antibody-mediated rejection in alloimmunized baboons. Kidney Int., 2010, 78(2), 152–159.
Chen, G., Sequeira, F., Tyan, D. B.: Novel C1q assay reveals a clinically relevant subset of human leukocyte antigen antibodies independent of immunoglobulin G strength on single antigen beads. Hum. Immunol., 2011, 72(10), 849–858.
Lachmann, N., Todorova, K., Schulze, H., et al.: Systematic comparison of four cell- and Luminex-based methods for assessment of complement-activating HLA antibodies. Transplantation, 2013, 95(5), 694–700.
Wahrmann, M., Exner, M., Regele, H., et al.: Flow cytometry based detection of HLA alloantibody mediated classical complement activation. J. Immunol. Methods, 2003, 275(1–2), 149–160.
Wahrmann, M., Exner, M., Schillinger, M., et al.: Pivotal role of complement-fixing HLA alloantibodies in presensitized kidney allograft recipients. Am. J. Transplant., 2006, 6(5 Pt 1), 1033–1041.
Tyan, D. B.: New approaches for detecting complement-fixing antibodies. Curr. Opin. Organ. Transplant., 2012, 17(4), 409–415.
Chin, C., Chen, G., Sequeria, F., et al.: Clinical usefulness of a novel C1q assay to detect immunoglobulin G antibodies capable of fixing complement in sensitized pediatric heart transplant patients. J. Heart Lung Transplant., 2011, 30(2), 158–163.
Loupy, A., Lefaucheur, C., Vernerey, D., et al.: Complement-binding anti-HLA antibodies and kidney-allograft survival. N. Engl. J. Med., 2013, 369(13), 1215–1226.
Yabu, J. M., Higgins, J. P., Chen, G., et al.: C1q-fixing human leukocyte antigen antibodies are specific for predicting transplant glomerulopathy and late graft failure after kidney transplantation. Transplantation, 2011, 91(3), 342–347.
Terasaki, P. I.: Humoral theory of transplantation. Am. J. Transplant., 2003, 3(6), 665–673.
Lefaucheur, C., Nochy, D., Andrade, J., et al.: Comparison of combination plasmapheresis/IVIg/anti-CD20 versus high-dose IVIg in the treatment of antibody-mediated rejection. Am. J. Transplant., 2009, 9(5), 1099–1107.