供者特异性抗体在异基因造血干细胞移植中的研究进展
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摘要
胞在allo-HSCT中较为常见。部分患者移植前或移植后存在供者特异性抗体,此类抗体可能引起植入失败和造血恢复延迟等移植并发症,影响患者的移植效果。识别供者特异性抗体的高危人群并对高危人群进行抗体检测,对于抗体阳性的患者进行及时的干预对于改善HLA不全相合造血干细胞移植的效果有重要意义。本文就供者特异性抗体流行病学、风险因素、供者特异性抗体对于非亲缘供者及单倍体相合HSC供者的allo-HSCT的影响、供者源的抗HLA抗体对于移植的影响以及供者特异性抗体的脱敏治疗做一综述。
Allogeneic hematopoietic stem cell transplantation( allo-HSCT) is w idely used in the treatment of hematological diseases,HLA incompatibility is displayed in most cases. Some patients have prestored donor-specific antibodies( DSA) or new emerging antibodies after transplantation. Donor-specific antibodies may cause graft failure and poor graft function,and affect transplant outcome. It is important to identify high risk candidates,assay antibodies and give proper intervention for improving the outcome of allo-HSCT. In this review,the research progress of DSA in allo-HSCT is summarized, including DSA prevalence, risk factors, the role of prestored DSA in unrelated and haploidentcal HSCT,the effect of donor derived antibodies in transplantation and desensitization therapy.
Allogeneic hematopoietic stem cell transplantation( allo-HSCT) is w idely used in the treatment of hematological diseases,HLA incompatibility is displayed in most cases. Some patients have prestored donor-specific antibodies( DSA) or new emerging antibodies after transplantation. Donor-specific antibodies may cause graft failure and poor graft function,and affect transplant outcome. It is important to identify high risk candidates,assay antibodies and give proper intervention for improving the outcome of allo-HSCT. In this review,the research progress of DSA in allo-HSCT is summarized, including DSA prevalence, risk factors, the role of prestored DSA in unrelated and haploidentcal HSCT,the effect of donor derived antibodies in transplantation and desensitization therapy.
引文
1 Xu LP,Wu DP,Han MZ,et al. A review of hematopoietic cell transplantation in China:data and trends during 2008-2016. Bone Marrow Transplant,2017; 52(11):1512-1518.
2 Zhang R. Donor-specific antibodies in kidney transplant recipients.Clin J Am Soc Nephrol,2018; 13(1):182-192.
3 Wong KL,Taner T,Smith BH,et al. Importance of routine antihuman/leukocyte antibody monitoring:de novo donor specific antibodies are associated with rejection and allograft vasculopathy after heart transplantation. Circulation,2017; 136(14):1350-1352.
4 Tikkanen JM,Singer LG,Kim SJ,et al. De novo DQ donor-specific antibodies are associated with chronic lung allograft dysfunction after lung transplantation. Am J Respir Crit Care Med,2016; 194(5):596-606.
5 Ciurea SO,Thall PF,Wang X,et al. Donor-specific anti-HLA Abs and graft failure in matched unrelated donor hematopoietic stem cell transplantation. Blood,2011; 118(22):5957-5964.
6 Yoshihara S,Maruya E,Taniguchi K,et al. Risk and prevention of graft failure in patients with preexisting donor-specific HLA antibodies undergoing unmanipulated haploidentical SCT. Bone Marrow Transplant,2012; 47(4):508-515.
7 Gladstone DE,Bettinotti MP. HLA donor-specific antibodies in allogeneic hematopoietic stem cell transplantation:challenges and opportunities. Hematology Am Soc Hematol Educ Program,2017;2017(1):645-650.
8 Okabe Y,Noguchi H,Miyamoto K,et al. Preformed C1q-binding donor-specific anti-HLA antibodies and graft function after kidney transplantation. Transplant Proc,2018; 50(10):3460-3466.
9 Morin-Zorman S,Loiseau P,Taupin JL,et al. Donor-specific anti-HLA antibodies in allogeneic hematopoietic stem cell transplantation. Front Immunol. 2016; 7:307.
10 Huo MR,Xu YJ,Zhai SZ,et al. Prevalence and risk factors of antibodies to human leukocyte antigens in haploidentical stem cell transplantation candidates:A multi-center study. Hum Immunol,2018; 79(9):672-677.
11 Xu H,Chilton PM,Tanner MK,et al. Humoral immunity is the dominant barrier for allogeneic bone marrow engraftment in sensitized recipients. Blood,2006; 108(10):3611-3619,
12 Yabe H,Morimoto T,Takakura H,et al. Post-transplantation-emerging anti-HLA DQA1/DQB1 antibody possibly respon-sible for graft rejection after myeloablative-unrelated marrow grafting.Bone Marrow Transplant,2016; 51(4):601-603.
13 Ciurea SO,Thall PF,Milton DR,et al. Complement-binding donor-specific anti-HLA antibodies and risk of primary graft failure in hematopoietic stem cell transplantation. Biol Blood Marrow Transplant,2015; 21(8):1392-1398.
14 Chang YJ,Zhao XY,Xu LP,et al. Donor-specific anti-human leukocyte antigen antibodies were associated with primary graft failure after unmanipulated haploidentical blood and marrow transplantation:a prospective study with randomly assigned training and validation sets. J Hematol Oncol,2015; 10(8):84.
15 Hanajiri R,Murata M,Sugimoto K,et al. Integration of humoral and cellular HLA-specific immune responses in cord blood allograft rejection. Bone Marrow Transplant,2015; 50(9):1187-1194.
16 Nordlander A,Mattsson J,Sundberg B,et al. Novel anti-bodies to the donor stem cell population CD34+/VEGFR-2+are associated with rejection after hematopoietic stem cell transplantation. Transplantation,2008; 86(5):686-696.
17 Taylor PA,Ehrhardt MJ,Roforth MM,et al. Preformed antibody,not primed T cells,is the initial and major barrier to bone marrow engraftment in allosensitized recipients. Blood,2007; 109(3):1307-1315.
18 Spellman S,Bray R,Rosen-Bronson S,et al. The detection of donor-directed,HLA-specific alloantibodies in recipients of unrelated hematopoietic cell transplantation is predictive of graft failure.Blood,2010; 115(13):2704-2708.
19 Cluzeau T,Lambert J,Raus N,et al. Risk factors and outcome of graft failure after HLA matched and mismatched unrelated donor hematopoietic stem cell transplantation:a study on behalf of SFGMTC and SFHI. Bone Marrow Transplant,2016; 51(5):687-691.
20 Woolfrey A,Wang T,Lee SJ,et al. Donor-specific anti-HLA antibodies in unrelated hematopoietic cell transplantation for nonmalignant disorders. Bone Marrow Transplant,2018 19. doi:10.1038/s41409-018-0334-y.(该文献目前尚无卷期页数信息)
21 Hefazi M,Hogan WJ,Wakefield LL,et al. The association of de novo anti-HLA-DPB1 donor-specific antibody formation and primary graft failure after allogeneic hematopoietic cell transplantation.Hum Immunol,2018; 79(12):861-864.
22 Zhao X,Zhao X,Huo M,et al. Donor-specific anti-human leukocyte antigen antibodies predict prolonged isolated thrombocytopenia and inferior outcomes of haploidentical hematopoietic stem cell transplantation. J Immunol Res,2017; 2017:1043836.
23 张荣莉,郑晓辉,周卢琨,等.供者特异性HLA抗体对单倍体相合造血干细胞植入的影响.中华血液学杂志,2018; 39(3):190-195.
24 Zou J,Romee R,Slade M,et al. Untreated donor specific antibodies against HLA are associated with poor outcomes in peripheral blood haploidentical hematopoietic cell transplantation. Bone Marrow Transplant,2017; 52(6):898-901.
25 Taniguchi K,Yoshihara S,Maruya E,et al. Donor-derived HLA antibody production in patients undergoing SCT from HLA antibody-positive donors. Bone Marrow Transplant,2012; 47(10):1338-1342.
26 Delbos F,Barhoumi W,Cabanne L,et al. Donor immunization against human leukocyte class II antigens is a risk factor for graftversus-host disease. Biol Blood Marrow Transplant,2016; 22(2):292-299.
27 Kongtim P,Cao K,Ciurea SO. Donor specific anti-HLA antibody and risk of Graft failure in haploidentical stem cell transplantation.Adv Hematol,2016; 2016:4025073.
28 Bramanti S,Nocco A,Mauro E,et al. Desensitization with plasma exchange in a patient with human leukocyte antigen donor-specific antibodies before T-cell-replete haploidentical transplantation.Transfusion,2016; 56(5):1096-1100.
29 Yamashita T,Ikegame K,Kojima H,et al. Effective desensitization of donor-specific HLA antibodies using platelet transfusion bearing targeted HLA in a case of HLA-mismatched allogeneic stem cell transplantation. Bone Marrow Transplant,2017; 52(5):794-796.
30 Ciurea SO,Cao Kai,Fernadez-Vina M,et al. The European Society for Blood and Marrow Transplantation(EBMT)consensus guidelines for the detection and treatment of donor specific anti-HLA antibodies(DSA)in haploidentical hematopoietic cell transplantation.Bone Marrow Transplant,2018; 53(5):521-534.
2 Zhang R. Donor-specific antibodies in kidney transplant recipients.Clin J Am Soc Nephrol,2018; 13(1):182-192.
3 Wong KL,Taner T,Smith BH,et al. Importance of routine antihuman/leukocyte antibody monitoring:de novo donor specific antibodies are associated with rejection and allograft vasculopathy after heart transplantation. Circulation,2017; 136(14):1350-1352.
4 Tikkanen JM,Singer LG,Kim SJ,et al. De novo DQ donor-specific antibodies are associated with chronic lung allograft dysfunction after lung transplantation. Am J Respir Crit Care Med,2016; 194(5):596-606.
5 Ciurea SO,Thall PF,Wang X,et al. Donor-specific anti-HLA Abs and graft failure in matched unrelated donor hematopoietic stem cell transplantation. Blood,2011; 118(22):5957-5964.
6 Yoshihara S,Maruya E,Taniguchi K,et al. Risk and prevention of graft failure in patients with preexisting donor-specific HLA antibodies undergoing unmanipulated haploidentical SCT. Bone Marrow Transplant,2012; 47(4):508-515.
7 Gladstone DE,Bettinotti MP. HLA donor-specific antibodies in allogeneic hematopoietic stem cell transplantation:challenges and opportunities. Hematology Am Soc Hematol Educ Program,2017;2017(1):645-650.
8 Okabe Y,Noguchi H,Miyamoto K,et al. Preformed C1q-binding donor-specific anti-HLA antibodies and graft function after kidney transplantation. Transplant Proc,2018; 50(10):3460-3466.
9 Morin-Zorman S,Loiseau P,Taupin JL,et al. Donor-specific anti-HLA antibodies in allogeneic hematopoietic stem cell transplantation. Front Immunol. 2016; 7:307.
10 Huo MR,Xu YJ,Zhai SZ,et al. Prevalence and risk factors of antibodies to human leukocyte antigens in haploidentical stem cell transplantation candidates:A multi-center study. Hum Immunol,2018; 79(9):672-677.
11 Xu H,Chilton PM,Tanner MK,et al. Humoral immunity is the dominant barrier for allogeneic bone marrow engraftment in sensitized recipients. Blood,2006; 108(10):3611-3619,
12 Yabe H,Morimoto T,Takakura H,et al. Post-transplantation-emerging anti-HLA DQA1/DQB1 antibody possibly respon-sible for graft rejection after myeloablative-unrelated marrow grafting.Bone Marrow Transplant,2016; 51(4):601-603.
13 Ciurea SO,Thall PF,Milton DR,et al. Complement-binding donor-specific anti-HLA antibodies and risk of primary graft failure in hematopoietic stem cell transplantation. Biol Blood Marrow Transplant,2015; 21(8):1392-1398.
14 Chang YJ,Zhao XY,Xu LP,et al. Donor-specific anti-human leukocyte antigen antibodies were associated with primary graft failure after unmanipulated haploidentical blood and marrow transplantation:a prospective study with randomly assigned training and validation sets. J Hematol Oncol,2015; 10(8):84.
15 Hanajiri R,Murata M,Sugimoto K,et al. Integration of humoral and cellular HLA-specific immune responses in cord blood allograft rejection. Bone Marrow Transplant,2015; 50(9):1187-1194.
16 Nordlander A,Mattsson J,Sundberg B,et al. Novel anti-bodies to the donor stem cell population CD34+/VEGFR-2+are associated with rejection after hematopoietic stem cell transplantation. Transplantation,2008; 86(5):686-696.
17 Taylor PA,Ehrhardt MJ,Roforth MM,et al. Preformed antibody,not primed T cells,is the initial and major barrier to bone marrow engraftment in allosensitized recipients. Blood,2007; 109(3):1307-1315.
18 Spellman S,Bray R,Rosen-Bronson S,et al. The detection of donor-directed,HLA-specific alloantibodies in recipients of unrelated hematopoietic cell transplantation is predictive of graft failure.Blood,2010; 115(13):2704-2708.
19 Cluzeau T,Lambert J,Raus N,et al. Risk factors and outcome of graft failure after HLA matched and mismatched unrelated donor hematopoietic stem cell transplantation:a study on behalf of SFGMTC and SFHI. Bone Marrow Transplant,2016; 51(5):687-691.
20 Woolfrey A,Wang T,Lee SJ,et al. Donor-specific anti-HLA antibodies in unrelated hematopoietic cell transplantation for nonmalignant disorders. Bone Marrow Transplant,2018 19. doi:10.1038/s41409-018-0334-y.(该文献目前尚无卷期页数信息)
21 Hefazi M,Hogan WJ,Wakefield LL,et al. The association of de novo anti-HLA-DPB1 donor-specific antibody formation and primary graft failure after allogeneic hematopoietic cell transplantation.Hum Immunol,2018; 79(12):861-864.
22 Zhao X,Zhao X,Huo M,et al. Donor-specific anti-human leukocyte antigen antibodies predict prolonged isolated thrombocytopenia and inferior outcomes of haploidentical hematopoietic stem cell transplantation. J Immunol Res,2017; 2017:1043836.
23 张荣莉,郑晓辉,周卢琨,等.供者特异性HLA抗体对单倍体相合造血干细胞植入的影响.中华血液学杂志,2018; 39(3):190-195.
24 Zou J,Romee R,Slade M,et al. Untreated donor specific antibodies against HLA are associated with poor outcomes in peripheral blood haploidentical hematopoietic cell transplantation. Bone Marrow Transplant,2017; 52(6):898-901.
25 Taniguchi K,Yoshihara S,Maruya E,et al. Donor-derived HLA antibody production in patients undergoing SCT from HLA antibody-positive donors. Bone Marrow Transplant,2012; 47(10):1338-1342.
26 Delbos F,Barhoumi W,Cabanne L,et al. Donor immunization against human leukocyte class II antigens is a risk factor for graftversus-host disease. Biol Blood Marrow Transplant,2016; 22(2):292-299.
27 Kongtim P,Cao K,Ciurea SO. Donor specific anti-HLA antibody and risk of Graft failure in haploidentical stem cell transplantation.Adv Hematol,2016; 2016:4025073.
28 Bramanti S,Nocco A,Mauro E,et al. Desensitization with plasma exchange in a patient with human leukocyte antigen donor-specific antibodies before T-cell-replete haploidentical transplantation.Transfusion,2016; 56(5):1096-1100.
29 Yamashita T,Ikegame K,Kojima H,et al. Effective desensitization of donor-specific HLA antibodies using platelet transfusion bearing targeted HLA in a case of HLA-mismatched allogeneic stem cell transplantation. Bone Marrow Transplant,2017; 52(5):794-796.
30 Ciurea SO,Cao Kai,Fernadez-Vina M,et al. The European Society for Blood and Marrow Transplantation(EBMT)consensus guidelines for the detection and treatment of donor specific anti-HLA antibodies(DSA)in haploidentical hematopoietic cell transplantation.Bone Marrow Transplant,2018; 53(5):521-534.