vtioВестник трансплантологии и искусственных органовRussian Journal of Transplantology and Artificial Organs1995-1191Academician V.I.Shumakov National Medical Research Center of Transplantology and Artificial Organs", Ministry of Health of the Russian Federation10.15825/1995-1191-2011-1-84-91vtio-364Research ArticleОбзор литературыLiterature ReviewsРОЛЬ ПРЕДСУЩЕСТВУЮЩИХ И DE NOVO АНТИДОНОРСКИХ АНТИТЕЛ ПРИ ТРАНСПЛАНТАЦИИ ПОЧКИTHE ROLE OF PRE-TRANSPLANT AND DE NOVO ALLOANTIBODIES IN KIDNEY TRANSPLANTATIONСушковА. И.SushkovA. I.АбрамоваВ. Ю.AbramovV. Y.МойсюкЯ. Г.MoysyukY. G.moysyuktrans@list.ruФГУ «Федеральный научный центр трансплантологии и искусственных органов им. академика В.И. Шумакова» Минздравсоцразвития РФ, МоскваРоссияAcadimician V.I. Shumakov Federal Research Center of Transplantology and Artificial Organs, MoscowRussian Federation201109062014131ВЕСТНИК ТРАНСПЛАНТОЛОГИИ И ИСКУССТВЕННЫХ ОРГАНОВ том XIII No 1–20118491Copyright © Сушков А.И., Абрамова В.Ю., Мойсюк Я.Г., 20112011Сушков А.И., Абрамова В.Ю., Мойсюк Я.Г.Sushkov A.I., Abramov V.Y., Moysyuk Y.G.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://journal.transpl.ru/vtio/article/view/364

Реципиенты почки могут иметь предсуществующие антидонорские антитела или вырабатывать de novo анти-HLA- или не-анти-HLA-антитела после трансплантации. Указанные антитела могут быть донор- специфическими (ДС) и не-донор-специфическими (не-ДС), их присутствие в сыворотке пациента способно повышать риск развития острого или хронического отторжения и ухудшать выживаемость трансплантата. Использование новых высокочувствительных и специфичных методов идентификации анти-HLA-антител как до, так и после трансплантации позволяет выделить группу пациентов, пред- расположенных к развитию ранних или поздних дисфункций трансплантата. Более того, определение уровня сенсибилизации до пересадки позволяет адекватно использовать иммуномодулирующие аген- ты и плазмаферез для элиминации анти-HLA-антител или снижения их продукции. В статье рассма- тривается связь между результатами трансплантации почки и наличием предсуществующих и de novo антител. 

Kidney transplant recipients may have pre-transplant alloantibodies or develop de novo anti-HLA and non- HLA antibodies after transplantation. Although these antibodies may be donor-specific or non-donor-specific, their presence may increase the risk for acute and chronic rejection, thereby decreasing allograft survival. The introduction of high sensitive and specific methods to detect anti-HLA antibodies, both before and after trans- plantation, will help to define transplant recipients who might be at increased risk for early or late allograft failure. Moreover, knowledge of alloantibody status before transplantation may help to guide the appropriate use of immunomodulatory agents and plasmapheresis to remove anti-HLA antibodies or downregulate their production. The review focuses on the associations between renal graft outcome and pre-transplant and de novo alloantibodies. 

трансплантация почкидонор-специфические антителаанти-HLA-антителаотторжение трансплантатаkidney transplantationdonor-specifi c antibodiesanti-HLA antibodiesgraft rejectionReferencesАбрамов В.Ю. и соавт. Ретроспективный анализ изменений в течение одного года содержания и специфичности предсуществующих антител // Междуна- родный нефрологический симпозиум «Современные аспекты заместительной терапии при почечной недо- статочности». М. 1998. С. 105–106.Абрамов В.Ю. и соавт. Ретроспективный анализ изменений в течение одного года содержания и специфичности предсуществующих антител // Междуна- родный нефрологический симпозиум «Современные аспекты заместительной терапии при почечной недо- статочности». М. 1998. С. 105–106.Зарецкая Ю.М. Роль большого комплекса гистосов- местимости в выживаемости аллогенного транс- плантата // Клиническая иммуногенетика. М.: Меди- цина, 1983. С. 108–125.Зарецкая Ю.М. Роль большого комплекса гистосов- местимости в выживаемости аллогенного транс- плантата // Клиническая иммуногенетика. М.: Меди- цина, 1983. С. 108–125.Морозова В.В. и соавт. Более половины больных, ожидающих повторной пересадки почки, одновре- менно сенсибилизированы против антигенов HLA класса I и класса II // Клиническая трансплантация органов (актуальные вопросы). М. 2007. С. 163–164.Морозова В.В. и соавт. Более половины больных, ожидающих повторной пересадки почки, одновре- менно сенсибилизированы против антигенов HLA класса I и класса II // Клиническая трансплантация органов (актуальные вопросы). М. 2007. С. 163–164.Ильинский И.М. и соавт. Патоморфология транс- плантированных органов // Трансплантология. Ру- ководство для врачей / Под ред. В.И. Шумакова. М. 2006. С. 472–538.Ильинский И.М. и соавт. Патоморфология транс- плантированных органов // Трансплантология. Ру- ководство для врачей / Под ред. В.И. Шумакова. М. 2006. С. 472–538.Снелл Д., Доссе Ж., Нэтенсон С. Совместимость тка- ней. М.: «Мир». 1979. 501 С.Снелл Д., Доссе Ж., Нэтенсон С. Совместимость тка- ней. М.: «Мир». 1979. 501 С.Шумаков В.И., Хубутия М.Ш., Белецкая Л.В. Оттор- жение гуморального типа при аллотрансплантации сердца. Тверь: ООО «Издательство «Триада». 2003.Шумаков В.И., Хубутия М.Ш., Белецкая Л.В. Оттор- жение гуморального типа при аллотрансплантации сердца. Тверь: ООО «Издательство «Триада». 2003.Akalin E. et al. Addition of plasmapheresis decreases the incidence of acute antibody-mediated rejection in sen- sitized patients with strong donor-specific antibodies // Clin. J. Am. Soc. Nephrol. 2008. Vol. 3 (4). P. 1160–1167.Akalin E. et al. Addition of plasmapheresis decreases the incidence of acute antibody-mediated rejection in sen- sitized patients with strong donor-specific antibodies // Clin. J. Am. Soc. Nephrol. 2008. Vol. 3 (4). P. 1160–1167.Bartel G. et al. Peritransplant immunoadsorption for po- sitive crossmatch deceased donor kidney transplantati- on // Am. J. Transplant. 2010. Vol. 10 (9). P. 2033–2042.Bartel G. et al. Peritransplant immunoadsorption for po- sitive crossmatch deceased donor kidney transplantati- on // Am. J. Transplant. 2010. Vol. 10 (9). P. 2033–2042.Breimer M.E. et al. Multicenter evaluation of a novel en- dothelial cell crossmatch test in kidney transplantation // Transplantation. 2009. Vol. 87 (4). P. 549–556.Breimer M.E. et al. Multicenter evaluation of a novel en- dothelial cell crossmatch test in kidney transplantation // Transplantation. 2009. Vol. 87 (4). P. 549–556.Bryan C.F. et al. Long-term graft survival is improved in cadaveric renal retransplantation by flow cytometric crossmatching // Transplantation. 1998. Vol. 66 (12). P. 1827–1832.Bryan C.F. et al. Long-term graft survival is improved in cadaveric renal retransplantation by flow cytometric crossmatching // Transplantation. 1998. Vol. 66 (12). P. 1827–1832.Cinti P. et al. Alloantibodies and outcomes of deceased donor kidney allografts // Hum. Immunol. 2009. Vol. 70 (8). P. 651–654.Cinti P. et al. Alloantibodies and outcomes of deceased donor kidney allografts // Hum. Immunol. 2009. Vol. 70 (8). P. 651–654.Dausset J., H. Brecy. Identical nature of the leucocyte antigens detectable in monozygotic twins by means of immune iso-leuco-agglutinins // Nature. 1957. Vol. 180 (4599). P. 1430.Dausset J., H. Brecy. Identical nature of the leucocyte antigens detectable in monozygotic twins by means of immune iso-leuco-agglutinins // Nature. 1957. Vol. 180 (4599). P. 1430.Davenport A. et al. Development of cytotoxic antibo- dies following renal allograft transplantation is associ- ated with reduced graft survival due to chronic vascular rejection // Nephrol. Dial. Transplant. 1994. Vol. 9 (9). P. 1315–1319.Davenport A. et al. Development of cytotoxic antibo- dies following renal allograft transplantation is associ- ated with reduced graft survival due to chronic vascular rejection // Nephrol. Dial. Transplant. 1994. Vol. 9 (9). P. 1315–1319.Feucht H.E. et al. Capillary deposition of C4d comple- ment fragment and early renal graft loss // Kidney Int. 1993. Vol. 43 (6). P. 1333–1338.Feucht H.E. et al. Capillary deposition of C4d comple- ment fragment and early renal graft loss // Kidney Int. 1993. Vol. 43 (6). P. 1333–1338.Gautier A.C. et al. MICA compatibility and immuniza- tion in third kidney transplantations // Transplant. Proc. 2009. Vol. 41 (2). P. 663–665.Gautier A.C. et al. MICA compatibility and immuniza- tion in third kidney transplantations // Transplant. Proc. 2009. Vol. 41 (2). P. 663–665.Gebel H.M., Lebeck L.K. Crossmatch procedures used in organ transplantation // Clin. Lab. Med. 1991. Vol. 11 (3). P. 603–620.Gebel H.M., Lebeck L.K. Crossmatch procedures used in organ transplantation // Clin. Lab. Med. 1991. Vol. 11 (3). P. 603–620.Gorer P.A., Amos D.B. Passive immunity in mice against C57BL leukosis E.L. 4 by means of iso-immune serum // Cancer Res. 1956. Vol. 16 (4). P. 338–343.Gorer P.A., Amos D.B. Passive immunity in mice against C57BL leukosis E.L. 4 by means of iso-immune serum // Cancer Res. 1956. Vol. 16 (4). P. 338–343.Hamawi K. et al. Use of bortezomib for treatment of an- tibody medicated rejection in kidney transplant recipi- ents-case report // Clin. Transpl. 2009. P. 407–414.Hamawi K. et al. Use of bortezomib for treatment of an- tibody medicated rejection in kidney transplant recipi- ents-case report // Clin. Transpl. 2009. P. 407–414.Hankey K.G. et al. MIC expression in renal and pan- creatic allografts // Transplantation. 2002. Vol. 73 (2). P. 304–306.Hankey K.G. et al. MIC expression in renal and pan- creatic allografts // Transplantation. 2002. Vol. 73 (2). P. 304–306.Hardinger K.L., Alford K., Murillo D. Bortezomib for acute humoral rejection in two repeat transplant recipi- ents // Clin. Transpl. 2009. P. 479–483.Hardinger K.L., Alford K., Murillo D. Bortezomib for acute humoral rejection in two repeat transplant recipi- ents // Clin. Transpl. 2009. P. 479–483.Heidt S. et al. Bortezomib affects the function of human B cells: possible implications for desensitization proto- cols // Clin. Transpl. 2009. P. 387–392.Heidt S. et al. Bortezomib affects the function of human B cells: possible implications for desensitization proto- cols // Clin. Transpl. 2009. P. 387–392.Hourmant M. et al. Frequency and clinical implications of development of donor-specific and non-donor-speci- fic HLA antibodies after kidney transplantation // J. Am. Soc. Nephrol. 2005. Vol. 16 (9). P. 2804–2812.Hourmant M. et al. Frequency and clinical implications of development of donor-specific and non-donor-speci- fic HLA antibodies after kidney transplantation // J. Am. Soc. Nephrol. 2005. Vol. 16 (9). P. 2804–2812.Iwaki Y. et al. Flow cytometry crossmatching in human cadaver kidney transplantation // Transplant. Proc. 1987. Vol. 19 (1 Pt 1). P. 764–746.Iwaki Y. et al. Flow cytometry crossmatching in human cadaver kidney transplantation // Transplant. Proc. 1987. Vol. 19 (1 Pt 1). P. 764–746.Jordan S.C. et al. Advances in diagnosing and managing antibody-mediated rejection // Pediatr. Nephrol. 2010. Vol. 25 (10). P. 2035–2045; quiz 2045–2048.Jordan S.C. et al. Advances in diagnosing and managing antibody-mediated rejection // Pediatr. Nephrol. 2010. Vol. 25 (10). P. 2035–2045; quiz 2045–2048.Lachmann N. et al. Antihumoral rejection therapy by proteasome inhibitor bortezomib: a case series // Clin. Transpl. 2009. P. 351–358.Lachmann N. et al. Antihumoral rejection therapy by proteasome inhibitor bortezomib: a case series // Clin. Transpl. 2009. P. 351–358.Lederer S.R. et al. Impact of humoral alloreactivity early after transplantation on the long-term survival of renal allografts // Kidney Int. 2001. Vol. 59 (1). P. 334–341.Lederer S.R. et al. Impact of humoral alloreactivity early after transplantation on the long-term survival of renal allografts // Kidney Int. 2001. Vol. 59 (1). P. 334–341.Lee P.C. et al. All chronic rejection failures of kidney trans- plants were preceded by the development of HLA antibo- dies // Transplantation. 2002. Vol. 74 (8). P. 1192–1194.Lee P.C. et al. All chronic rejection failures of kidney trans- plants were preceded by the development of HLA antibo- dies // Transplantation. 2002. Vol. 74 (8). P. 1192–1194.Lee P.C. et al. HLA-specific antibodies developed in the first year posttransplant are predictive of chronic rejec- tion and renal graft loss // Transplantation. 2009. Vol. 88 (4). P. 568–574.Lee P.C. et al. HLA-specific antibodies developed in the first year posttransplant are predictive of chronic rejec- tion and renal graft loss // Transplantation. 2009. Vol. 88 (4). P. 568–574.Lefaucheur C. et al. Preexisting donor-specific HLA antibodies predict outcome in kidney transplantation // J. Am. Soc. Nephrol. 2010. Vol. 21 (8). P. 1398–1406.Lefaucheur C. et al. Preexisting donor-specific HLA antibodies predict outcome in kidney transplantation // J. Am. Soc. Nephrol. 2010. Vol. 21 (8). P. 1398–1406.Mai H.L. et al. Bortezomib in the treatment of antibody- mediated rejection-a report of 3 cases // Clin. Transpl. 2009. P. 361–368.Mai H.L. et al. Bortezomib in the treatment of antibody- mediated rejection-a report of 3 cases // Clin. Transpl. 2009. P. 361–368.Meier-Kriesche H.U., Schold J.D., Kaplan B. Long-term renal allograft survival: have we made significant progress or is it time to rethink our analytic and therapeutic strate- gies? // Am. J. Transplant. 2004. Vol. 4 (8). P. 1289–1295.Meier-Kriesche H.U., Schold J.D., Kaplan B. Long-term renal allograft survival: have we made significant progress or is it time to rethink our analytic and therapeutic strate- gies? // Am. J. Transplant. 2004. Vol. 4 (8). P. 1289–1295.Nishikawa K., Terasaki P.I. Annual trends and triple the- rapy – 1991–2000 // Clin. Transpl. 2001. P. 247–269.Nishikawa K., Terasaki P.I. Annual trends and triple the- rapy – 1991–2000 // Clin. Transpl. 2001. P. 247–269.Opelz G. Non-HLA transplantation immunity revealed by lymphocytotoxic antibodies // Lancet. 2005. Vol. 365 (9470). P. 1570–1576.Opelz G. Non-HLA transplantation immunity revealed by lymphocytotoxic antibodies // Lancet. 2005. Vol. 365 (9470). P. 1570–1576.Patel R., Terasaki P.I. Significance of the positive cross- match test in kidney transplantation // N. Engl. J. Med. 1969. Vol. 280 (14). P. 735–739.Patel R., Terasaki P.I. Significance of the positive cross- match test in kidney transplantation // N. Engl. J. Med. 1969. Vol. 280 (14). P. 735–739.Pei R. et al. Single human leukocyte antigen flow cy- tometry beads for accurate identification of human leu- kocyte antigen antibody specificities // Transplantation. 2003. Vol. 75 (1). P. 43–49.Pei R. et al. Single human leukocyte antigen flow cy- tometry beads for accurate identification of human leu- kocyte antigen antibody specificities // Transplantation. 2003. Vol. 75 (1). P. 43–49.Pei R. et al. Simultaneous HLA Class I and Class II anti- bodies screening with flow cytometry // Hum. Immunol. 1998. Vol. 59 (5). P. 313–322.Pei R. et al. Simultaneous HLA Class I and Class II anti- bodies screening with flow cytometry // Hum. Immunol. 1998. Vol. 59 (5). P. 313–322.Piazza A. et al. Posttransplant donor-specific antibody characterization and kidney graft survival // Transpl. Int. 2000. Vol. 13. Suppl. 1. P. S439–S443.Piazza A. et al. Posttransplant donor-specific antibody characterization and kidney graft survival // Transpl. Int. 2000. Vol. 13. Suppl. 1. P. S439–S443.Racca A.L. et al. Expression of HLA-G and MICA mRNA in renal allograft // Transpl. Immunol. 2009. Vol. 21 (1). P. 10–12.Racca A.L. et al. Expression of HLA-G and MICA mRNA in renal allograft // Transpl. Immunol. 2009. Vol. 21 (1). P. 10–12.Riethmuller S. et al. Donor-specific antibody levels and three generations of crossmatches to predict antibody- mediated rejection in kidney transplantation // Trans- plantation. 2010. Vol. 90 (2). P. 160–167.Riethmuller S. et al. Donor-specific antibody levels and three generations of crossmatches to predict antibody- mediated rejection in kidney transplantation // Trans- plantation. 2010. Vol. 90 (2). P. 160–167.Rodriguez P.C. et al. Detection of alloantibodies against non-HLA antigens in kidney transplantation by flow cyto- metry // Clin. Transplant. 2000. Vol. 14 (5). P. 472–478.Rodriguez P.C. et al. Detection of alloantibodies against non-HLA antigens in kidney transplantation by flow cyto- metry // Clin. Transplant. 2000. Vol. 14 (5). P. 472–478.Sanchez-Fructuoso A.I. et al. De novo anti-HLA antibo- dies in renal allograft recipients: a cross-section study // Transplant. Proc. 2010. Vol. 42 (8). p. 2874–2876.Sanchez-Fructuoso A.I. et al. De novo anti-HLA antibo- dies in renal allograft recipients: a cross-section study // Transplant. Proc. 2010. Vol. 42 (8). p. 2874–2876.Solez K. et al. Banff 07 classification of renal allograft pathology: updates and future directions // Am. J. Trans- plant. 2008. Vol. 8 (4). P. 753–760.Solez K. et al. Banff 07 classification of renal allograft pathology: updates and future directions // Am. J. Trans- plant. 2008. Vol. 8 (4). P. 753–760.Sumitran-Holgersson S. et al. Identification of the non- classical HLA molecules, mica, as targets for humoral im- munity associated with irreversible rejection of kidney al- lografts // Transplantation. 2002. Vol. 74 (2). P. 268–277.Sumitran-Holgersson S. et al. Identification of the non- classical HLA molecules, mica, as targets for humoral im- munity associated with irreversible rejection of kidney al- lografts // Transplantation. 2002. Vol. 74 (2). P. 268–277.Terasaki P.I. Humoral theory of transplantation // Am. J. Transplant. 2003. Vol. 3 (6). P. 665–673.Terasaki P.I. Humoral theory of transplantation // Am. J. Transplant. 2003. Vol. 3 (6). P. 665–673.Terasaki P.I., Kreisler M., Mickey R.M. Presensitization and kidney transplant failures // Postgrad. Med. J. 1971. Vol. 47 (544). P. 89–100.Terasaki P.I., Kreisler M., Mickey R.M. Presensitization and kidney transplant failures // Postgrad. Med. J. 1971. Vol. 47 (544). P. 89–100.Terasaki P.I., McClelland J.D. Microdroplet assay of hu- man serum cytotoxins // Nature. 1964. Vol. 204. P. 998– 1000.Terasaki P.I., McClelland J.D. Microdroplet assay of hu- man serum cytotoxins // Nature. 1964. Vol. 204. P. 998– 1000.Terasaki P.I., Ozawa M. Predicting kidney graft failure by HLA antibodies: a prospective trial // Am. J. Trans- plant. 2004. Vol. 4 (3). P. 438–443.Terasaki P.I., Ozawa M. Predicting kidney graft failure by HLA antibodies: a prospective trial // Am. J. Trans- plant. 2004. Vol. 4 (3). P. 438–443.Worthington J.E. et al. Posttransplantation production of donor HLA-specific antibodies as a predictor of renal transplant outcome // Transplantation. 2003. Vol. 75 (7). P. 1034–1040.Worthington J.E. et al. Posttransplantation production of donor HLA-specific antibodies as a predictor of renal transplant outcome // Transplantation. 2003. Vol. 75 (7). P. 1034–1040.Yuan X.P. et al. Kidney transplant in highly sensitized patients after desensitization with plasmapheresis and low-dose intravenous immunoglobulin // Exp. Clin. Transplant. 2010. Vol. 8 (2). P. 130–135.Yuan X.P. et al. Kidney transplant in highly sensitized patients after desensitization with plasmapheresis and low-dose intravenous immunoglobulin // Exp. Clin. Transplant. 2010. Vol. 8 (2). P. 130–135.Zhang, Q. et al. Development of posttransplant antido- nor HLA antibodies is associated with acute humoral rejection and early graft dysfunction // Transplantation. 2005. Vol. 79 (5). P. 591–598.Zhang, Q. et al. Development of posttransplant antido- nor HLA antibodies is associated with acute humoral rejection and early graft dysfunction // Transplantation. 2005. Vol. 79 (5). P. 591–598.

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