特集・総説（４４行）／Ｐ４９４～５０４＿総説　佐治（４Ｃ）

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1 494 Vol. 45, No. 5 HLA HLA HLA Transplantation and HLA antibody: posttransplantation HLA antibody monitoring and HLA type & screen to overcome technical and logistic limitations Hiroh SAJI HLA Laboratory, NPO The important role of preformed HLA antibodies in the outcome of organ transplants has been well demonstrated for the past 40 years. During this same period, the significance of HLA antibody formation after transplantation was largely ignored. Only in the past 10 years has it become increasingly clear that HLA antibodies formed posttransplantation are the major cause of allograft failure. On the basis of this new finding, in addition to pretransplantation antibody screening and crossmatch, monitoring for antibody development after 3, 6, 9, and 12 months, with yearly checks thereafter, is suggested. In stem cells bone marrow transplantation, HLA-identical donors have been employed for almost 40 years. However, nowadays HLA-mismatch unrelated transplantation using cord blood and related HLA haploidentical mismatch transplantation are becoming more popular. In both organ and stem cells transplantation, there are so-called logistic problems of donor lymphocytes for direct crossmatching with unrelated donors, especially in the setting of cord blood and cadaveric grafts. Herein, the author proposes HLA type & screen, an analog of type & screen in blood transfusion known as virtual crossmatch in the USA. This method also may partially solve another logistic problem: limited donor search for hypersensitized recipients. Recent technical developments of HLA antibody detection and identification of specificity are reviewed herein. Finally, the epitope of HLA antigens for antibodies is summarized, and probability of identification for immunodominant epitope and its clinical importance are mentioned. HLA antibody, transplantation, rejection, type & screen, virtual crossmatch, clinical monitoring HLA HLA WHO Committee Member of Nomenclature for Minor Histocompatibility Antigens.

2 HLA HLA 495 HLA ABO HLA HLA HLA HLA HLA PRA Panel reactive antibodies DSA DSA donor specific antibody ethnicity HLA HLA HLA HLA-A B Bw Cw HLA-DR DQ DP HLA single antigen coated beads HLA 1 DSA HLA HLA HLA LCT AHG-LCT AHG-LCT HLA 1 HLA HLA

3 496 Vol. 45, No. 5 HLA HLA / HLA HLA ELISA FCM Luminex R beads 100 Class Class HLA PE LABScan 100 R 100 PE HLA PE HLA HLA immunocomplex capture fluorescence analysis ICFA 2 1 ICFA HLA immunocomplex capture PE fluorescence analysis

4 HLA HLA 497 ICFA WAKFlow R HLA ICFA 2 HLA LABScreen PRA R OneLambda WAKFlow HLA MR R LCT HLA single antigen coated beads 3 HLA HLA HLA HLA 1 HLA OneLambda LABScreen Single Antigen Class R 31 A 50 B 16 C 1 LABScreen Single Antigen Class R 33 DR DRB1 DRB3 DR52 DRB4 DR53 DRB5 DR51 29 DQ 24 DP 1 HLA 3 HLA 24 HLA ABO Rho HLA HLA HLA HLA HLA

5 498 Vol. 45, No. 5 HLA Virtual Crossmatch 3-6 HLA HLA 20 HLA % 7 90% HLA 100 half-life

6 HLA HLA HLA cyclosporine tacrolimus FK-506 sirolimus mycophenolate mofetil MMF bortezomib clonal deletion 9 HLA 10 half-life HLA HLA HLA HLA DSA donor specific antibody DSA HLA MMF 11rituximab R B 12bortezomib R 13 Bortezomib mg/m 2 Day HLA bortezomib HLA Terasaki 14 bortezomib Clonal Deletion HLA HLA rituximab bortezomib HLA HLA HLA GVH HLA HLA HLA Haploidentical HLA HLA GVH HLA HLA Single antigen coated beads HLA DR DRB1 DR51 DRB 5 DR52 DRB3 DR53 DRB4 DRB HLA

7 500 Vol. 45, No. 5 DR single antigen coated beads DR15 DRB DR 51 DRB single antigen coated beads DR15 DR51 DR15 -DR15 -DR51 -DR51 DR15 DR16 -DR15 -DR16 DRB HLA Shared epitope SP HLA HLA HLA HLA HLA 15 HLA HLA HLA -A B 0801 HLA HLA

8 HLA HLA 501

9 502 Vol. 45, No. 5 HLA HLA DPB1 HLA

HLA HLA 503 HLA Excel 16 single antigen coated beads HLA Haploidentical HLA inherited paternal antigens 1 allele/ HLA SP Epigraph Excel 17 HLA HLA HLA immunodominant epitope HLA 17 1 Terasaki PI, Cai

10 HLA HLA 503 HLA Excel 16 single antigen coated beads HLA Haploidentical HLA inherited paternal antigens 1 allele/ HLA SP Epigraph Excel 17 HLA HLA HLA immunodominant epitope HLA 17 1 Terasaki PI, Cai J. Human leukocyte antigen antibodies and chronic rejection: from association to causation. Transplantation 2008; 86: Fujiwara K, Shimano K, Tanaka H, et al. Application of bead array technology to simultaneous detection of human leucocyte antigen and human platelet antigen antibodies. Vox Sang 2009; 96: Tambur AR, Ramon DS, Kaufman DB, et al. Perception versus reality?: Virtual crossmatch how to overcome some of the technical and logistic limitations. Am J Transplant 2009; 9: Gutman JA, McKinney SK, Pereira S, et al. Prospective monitoring for alloimmunization in cord blood transplantation: virtual crossmatch can be used to demonstrate donor-directed antibodies. Transplantation 2009; 287: Zachary AA, Sholander JT, Houp JA, et al. Using real data for a virtual crossmatch. Hum Immunol 2009; 70: Bingaman AW, Murphey CL, Palma-Vargas J, et al. A virtual crossmatch protocol significantly increases access of highly sensitized patients to deceased donor kidney transplantation. Transplantation 2008; 86: Fifteen years of HL-A: what is the importance of HLA compatibility for clinical outcome of renal transplantations? Vox Sang 1978; 34: Kaneku HK, Terasaki PI. Thirty years trend in kidney transplants: UCLA and UNOS Renal Transplant Registry. Clin Transpl 2006: 1-27.

11 504 Vol. 45, No. 5 9 Ashihara E, Tsuji H, Sakashita H, et al. Antidonor antibody in patients receiving ABO-identical and HLA-mismatched living donor liver transplants: effect on survival. Transplantation 2007; 83: Everly MJ, Terasaki PI. Monitoring and treating posttransplant human leukocyte antigen antibodies. Hum Immunol 2009; 70: Rebellato LM, Zadeh S, Ozawa M, et al. Mycophenolic acid may reduce donor specific HLA antibody strength in kidney transplant recipients. Am J Transplant 2009; 9 Suppl 2 : 641 Abstract. 12 Becker YT, Becker BN, Pirsch JD, et al. Rituximab as treatment for refractory kidney transplant rejection. Am J Transplant 2004; 4: Idica A, Kaneku H, Everly MJ, et al. Elimination of post-transplant donor-specific HLA antibodies with bortezomib. Clin Transpl 2008; Trivedi HL, Kaneku H, Terasaki PI, et al. Clonal deletion using total lymphoid irradiation with no maintenance immunosuppression in renal allograft recipients. Clin Transpl 2009, El-Awar N, Terasaki PI, Nguyen A, et al. Epitopes of human leukocyte antigen class I antibodies found in sera of normal healthy males and cord blood. Hum Immunol 2009; 70: Silva E, Alba A, Castro A, et al. Evaluation of HLA Matchmaker compatibility as predictor of graft survival and presence of Anti-HLA antibodies. Transplant Proc 2010; 42: Maruya E, Sasaki N, El-Awar N, et al. Immunogenic HLA class epitopes identified by humoral response to pregnancies. Clin Transpl 2008;

16 MHC 2018; 25 (1) 参加費 1 2, , ,000 会議等 :00 13: :00 13: :20 会場地図 TEL JR 350 m 57

16 MHC 2018; 25 (1) 参加費 1 2, , ,000 会議等 :00 13: :00 13: :20 会場地図 TEL JR 350 m 57 Major Histocompatibility Complex 2018; 25 (1): 56 82 抄録集 16 2018 3 3 7 2 4 43 TEL 06 6962 7001 594 1101 840 TEL 0725 56 1220 56 16 MHC 2018; 25 (1) 参加費 1 2,000 2 1,000 3 3,000 会議等 1 3 3 13:00 13:10 2 3

特集・総説（４４行）／Ｐ４９４～５０４＿総説 佐治（４Ｃ）

特集・総説（４４行）／Ｐ４９４～５０４＿総説　佐治（４Ｃ）