HLA HLA HLA-QC QCWS 11 DNA-QC 15 DNA-QC 16 DNA SSP 18 DNA SSO LABType 19 DNA SSO WAKFlow GenoSearch

Transcription

1 HLA HLA HLA-QC QCWS 11 DNA-QC 15 DNA-QC 16 DNA SSP 18 DNA SSO LABType 19 DNA SSO WAKFlow GenoSearch 21 DNA SBT 23 QC 25 QC 26 FCM FlowPRA 28 WAKFlow 29 LABScreen 31 LIFECODES MHC Instructions to Authors (updated on Feb. 19, 2019) Major Histocompatibility Complex Official Journal of Japanese Society for Histocompatibility and Immunogenetics JSHI

2 Major Histocompatibility Complex 2019; 26 (1): Frans Claas Immunohematology and Blood Transfusion, Leiden University Medical Center Transplantation of highly sensitized patients & HLA epitope matching to prevent sensitization Eric Spierings Laboratory of Translational Immunology, University Medical Center Utrecht T-cell epitopes in HLA-mismatched transplantations HLA B cell EPITOPE Frans Claas T cell EPITOPE Eric Spierings B cell EPITOPE T cell EPITOPE de novo DSA HLA DNA

3 MHC 2019; 26 (1) 28 2 TEL: QCWS HLA TEL: jshi2019@aichi-med-u.ac.jp 2

4 Major Histocompatibility Complex 2019; 26 (1): MHC Web nohe@hiroshima-u.ac.jp 1 3

5 MHC 2019; 26 (1) FAX MHC 2019 hlajimu@m.u-tokyo.ac.jp nohe@hiroshima-u.ac.jp 4

6 Major Histocompatibility Complex 2019; 26 (1): HLA TEL HLA HLA 2 HLA HLA HLA 3 HLA 5

7 Major Histocompatibility Complex 2019; 26 (1): 6 QC HLA HLA 1 HLA :30 20: WS1 HLA WS2-1 WS2-2 5 WS1 WS WS

8 Major Histocompatibility Complex 2019; 26 (1): HLA % 93 77% 3 2% % % 14 12% 11 9% % 6 5% % 77 59% % 2 2% 10 8% 1 1% 9 7% 3 2% % 61 50% 9 7% 3 2% % 14 19% 7

9 MHC 2019; 26 (1) 平成 30 年度 認定 HLA 検査技術者講習会アンケート集計結果 4 学会ホームページに掲載された 講習会テキストの事前確認の有無 あり 94 名 78% なし 27 名 22% 5 講習科目の種類は適切であったか 6 講習内容のレベルならびに講習テキストは適切であったか 7 講習時間は量的に適切であったか 8 回答者 121 名

10 30 HLA MHC 2019; 26 (1) 8 9 PDF HP HP QCWS HLA HLA HLA-G MHC NK MHC H25 27 H30 9

11 Major Histocompatibility Complex 2019; 26 (1): QC HLA WG HLA WG WG WG WG 10

12 Major Histocompatibility Complex 2019; 26 (1): HLA-QC 22 HLA-QC QCWS 1) 1) QCWS # HLA-QCWS 81 1 DNA-QC 74 QC DNA-QC QC 26 QCWS 4 9 QCWS HLA QC CD-R 111 MHC 2 QCWS DNA-QC DNA DNA HLA 3 DNA HLA # QCWS 1) 2) 3) 4) 5) 6) 7) 8) 9) 10) 11) 12) 8) 13) 14) 13) 15) 16) 1) 2) 3) 4) 5) 6) 7) 8) 9) 10) HLA 11) 12) 13) HLA 14) 15) 16) 11

13 MHC 2019; 26 (1) 第 22 回 HLA-QC ワークショップレポート 表1 第 22 回 HLA-QCWS 参加施設 胞を選定した 4 種類の購入細胞を培養した後 抽出し ②抗体と DNA の結果から正しく適合判定が行えるこ た DNA を約 100 ng/μl の濃度で 100 μl SSP 実施施設 とをテーマとして 指定した抗体試料と DNA 試料の測 は倍量 ずつ配布した これとは別に SSO ルミネッ 定結果による HLA クラス I とクラス II を対象とした仮 クス法の陰性コントロール DNase free water 50 μl を 想クロスマッチ 配布し 各施設で陰性コントロール データの取得を必 また 日本移植学会連携クロスマッチでは 抗体 QC 須とした で使用する試料を一部共用して実施した 抗体 QC のテーマは ①抗体検査が適正な操作過程に 3 解析報告と担当者 基づき正確に行えること ②エピトープと許容抗原によ り正確な抗体特異性解析が行えること ③検査結果から 解析は 主に前年度と同一担当者に それぞれの担当 導かれる総合判定結果を正しく報告できることの 3 点と 項目を入れ替えて依頼した 解析結果の公表は QCWS した 抗体試料は 本学会から提供依頼した日本赤十字 集会での報告 学会公式サイトへの掲載 データ集 CD-R の配布 学会誌への掲載の 4 通りとした 社に保管してある献血者由来の抗血清 4 種類を選定し た これらは 過去の QCWS で使用歴があり 当時の 集会では タイピング結果解析 DNA-QC と抗体検 解析結果に課題を見出した抗血清とした 血清化処理し 査結果解析 抗体 QC に分け それぞれ試料説明 検 た後 各施設に 1 ml ずつ配布した 査方法別解析 総合解析の順に報告した DNA-QC では クロスマッチについては 本年も参加希望施設からの 新表記法の問題点とその解説 評価点と操作工程の関係 募集参加として以下の 2 通りで実施することを提示し ソフトウェアの活用 ビーズカウントの問題 コンタミ それぞれ参加申込み時に受け付けた ネーションの状況などが報告された 抗体 QC では 総 ①配布検体の一部を使用しクロスマッチを正確に行え 合判定結果不一致であった要因 スクリーニング検査の ることをテーマとして 指定した抗体試料と各施設で準 位置づけ コントロールの重要性 バックグラウンド処 備した細胞で HLA クラス I を対象としたダイレクトク 理などが報告された 最後に総合討論として 公開バー ロスマッチ チャルクロスマッチ を企画し 各臨床部門の参加者を 12

14 22 HLA-QC MHC 2019; 26 (1) 1 DNA SSP SSO SSO SBT Sanger NGS 2 FCM FlowPRA # # # SSO LABType WAKFlow/ Genosearch # LABScreen WAKFlow LIFECODES 4 QCWS DNA DNA Ambiguity 1 DNA HLA-A, B, C, DRB1, DQB1, DPB1 IMGT/HLA HLA HLA-QC DNA 13

15 MHC 2019; 26 (1) 第 22 回 HLA-QC ワークショップレポート 表3 第 22 回 HLA-QC ワークショップレポート 抗体サンプルの総合結果 した 表 2 の 2 に達しない抗原として表示した HLA 遺伝子頻度 抗体試料は 参加各施設の総合判定結果を集計し は本学会 HLA 標準化委員会が公開している HLA 推定 HLA 遺伝子頻度 0.1% 以上の抗原に対する特異性につい アレル一覧表 JSHI 2018 年度版 を参照した 表 3 て記載した スコア 8 は 3 分の 2 以上の参加施設が これらの結果を各施設の結果の再確認 精度管理及び 陽性判定した抗原 スコア 1 は 3 分の 2 以上の参加 技術向上に活用していただきたい 施設が陰性判定した抗原 スコア 4 はどちらも 3 分 14

16 22 HLA-QC 22 HLA-QC DNA-QC 1) 1) 1 DNA-QC HLA-A, B, C, DRB1 QCWS 2 22ndDNA-QC 3 H3003 H3004 B44 A*33:03- C*14:03-B*44:03-DRB1*13:02 2 A*03:01-C*05:01-B*44:02-DRB1*13:01 48 HLA 1 HLA HLA 3 DNA 100 ng/μl 4 DNase free water SSO 21stQCWS 15

17 22 HLA-QC 22 HLA-QC DNA-QC 1) 1) 1 DNA-QC % % % 6 8.1% HLA-A B C DRB1 DRB3/4/5 DQB1 DPB1 DQA1 DPA1 SSO Luminex 74.3% QCWS HLA 2017 ambiguity HLA DNA A B C 3 B 11 C 1 BC 13 Luminex SSO 11 3 ambiguity H3003 DPA1*02:08 SSO ambiguity DPA1*02:01 DPA1*02:01 ambiguity HLA B SSO 16

18 22 HLA-QC MHC 2019; 26 (1) 17

19 22 HLA-QC 22 HLA-QC DNA SSP 1) 1) HLA Fusion SSP 2 false positive 1 5 SSP

20 22 HLA-QC 22 HLA-QC DNA SSO LABType 1) 1) 1 LABType % HLA-A HLA-B HLA-C HLA-DRB1 LABType SSO LABType HD LABType XR LABType HD HLA-A HLA-B HLA-C HLA-DRB1 LAB- Type XR HLA-C 2 LABType SSO HLA-A HLA-B HLA-C HLA-DRB1 1 HLA-DQ HLA-DP 4 HLA-DRB H3001 H Pmin/Nmax 22 QC LABType SSO HLA-B H3001 H3004 PCR LABType SSO HLA-DQ H3001 H3004 PCR LABType SSO HLA-C 1 19

21 MHC 2019; 26 (1) 4 22 HLA-QC 1 20

22 22 HLA-QC 22 HLA-QC DNA SSO WAKFlow, GenoSearch 1) 1) SSO Luminex % WAKFlow 41 3 GenoSearch 5 1 WAKFlow GenoSearch SSO SBT WAKFlow 5 GenoSearch 2 WAKFlow GenoSearch WAKFlow 41 HLA-A HLA-B HLA-DRB1 38 HLA-C 36 HLA-DQB1 23 HLA-DPB HLA-DQA1 GenoSearch 5 HLA-A -B -C -DRB P/N 5 D#37TG WAKFlow HLA- DRB1 22 QC PCR 3 4 P/N P/N 21

23 MHC 2019; 26 (1) 5 WAKFlow HLA-DRB1 D#37TG 4 22 HLA-QC WAKFlow SSO Luminex Genosearch 22

24 22 HLA-QC 22 HLA-QC DNA SBT 1) 1) 1 Sanger 4 3 Secore 1 AlleleSEQR Secore 3 utype7.1 AlleleSEQR 1 Assign-SBT v4.7 Secore Class II 3 DRB1 DQB1 exon 2, 3 DPB1 exon 2, 3, 4 Class I A B exon 2, 3, 4 2 exon 1, 2, 3, 4, 5 1 C exon 2, 3, 4 2 exon 1, 2, 3, 4, 5, 6, 7 1 AlleleSEQR Class I exon 2, 3, 4 DRB1 DPB1 exon 2 DQB1 exon 2, 3 NGS 3 2 All- Type NGS 1 ScisGo HLA AllType NGS 2 TypeStreamVisual 1 NGS engine ScisGo HLA Gems-HLA AllType NGS 2 A B C DQA1 DPA1 Full gene exon intron DRB1/3/4/5 DQB1 DPB1 exon 2 3 UTR ScisGo HLA DPA1 exon 2, 3, 4 A B C DRB1/3/4/5 DQB1 DPB1 DQA1 exon 2 1 Sanger Sanger 2 NGS NGS 2 Quality Value Quality Scores Sanger Sanger 4 Q20 Quality Value NGS NGS 3 Q20 Q20 3 Noise/Signal Sanger Sanger 4 Noise/Signal 8% 23

25 MHC 2019; 26 (1) 4 NGS % All- Type NGS 2 H3001 DQB1 Consensus Consensus 22 HLA-QC 3 Sanger NGS Sanger Quality Value NGS 24

26 22 HLA-QC 22 HLA-QC QC 1) 1) HLA-C IgM HLA QCWS QCWS High Background SH3001 SH3002 DQ SH3003 HLA SH3004 SH3002 SH3004 QC SH3003 II DQ CD 25

27 22 HLA-QC 22 HLA-QC QC 1) 1) 1 1 QC QCWS % % % HLA SH3002 SH3004 I II 97% SH3001 I 87% II 40% HLA LABScreen single antigen 41 WAKFlow HLA HR 21 LIFECODES 4 Luminex 2 HLA 2 1 HLA 0.1% HLA 0.67 SH A 47 A % B C 1 2.1% 2 90% I 43 II 23 I SH % 26

28 22 HLA-QC MHC 2019; 26 (1) II SH % LABScreen single antigen Lot MFI Score Calmed I II 1 DQ 3 QC 27

29 22 HLA-QC 22 HLA-QC FCM FlowPRA 1) 1) 1 Screening Class I 22 Class II 21 3 Single Antigen 2 3 %PRA Negative Control %PRA 3 SH3001 SH % LOT 5 FCM Luminex %PRA QCWS 28

30 22 HLA-QC 22 HLA-QC WAKFlow 1) 1) 1 QC 61 WAKFlow % MR Class I 15 MR Class II 8 HR Class I II 21 HR LABScreen Single Antigen LS-SA 6 HR WAKFlow MR Class I Class II BB PB BB SH3002 PB Median Median Index Median 2SD Index Lot Index SH3001 SH3002 SH3001 Class I 12/15 80% Class II 2/8 25% SH3002 Class II 6/8 75% 8 2 WAKFlow HR Class I Class II BB PB BB SH3002 PB SH Median Calmed Class I 2 Lot Class II 3 Lot V0A S27 Median Calmed 2SD SH3002 A24 Median Calmed Calmed 1,000 Calmed 1,000 1,000 HR LA-SA Average Calmed 1,000 LS-SA nmfi 1,000 Calmed 5,000 LS-SA Median Calmed 29

31 MHC 2019; 26 (1) 4 QCWS BB Median 500 MR HR Lot Lot Median 2SD Index Calmed MR 8 22 HLA-QC MR MR 1 HR Calmed Median 17 HR LS-SA LS-SA HR HR 30

32 22 HLA-QC 22 HLA-QC LABScreen 1) 1) 1 1 LABScreen Mixed 15 Multi 1 PRA 9 Single Antigen EDTA EDTA QCWS 2 Negative Control Serum Negative Control Serum 5 HLA Fusion NBG Ratio Normalized MFI Negative Control Serum 5 default background values OLINS Negative Control Serum OLINS Negative Control Serum OLINS OLINS QCWS Negative Control Serum 3 Negative Positive Control QC Negative Positive Control Bead Negative Positive Control Bead QCWS 4 SH3001 LABScreen Single Antigen Class II DRB1*04:04 16:02 Lot 3 LABScreen Single Antigen Normalized MFI Negative Control Serum Negative Positive Control Bead 31

33 MHC 2019; 26 (1) 4 HLA Fusion4.2 epitope HLA Fusion4.2 HLA Matchmaker HLA Fusion epitope HLA 22 HLA-QC epitope registry 22 QC 32

34 22 HLA-QC 22 HLA-QC LIFECODES 1) 1) 1) 1 4 LIFECODES LSA Single Antigen LSA 1 LSA HLA LSA HP 22 QCWS 2 4 LSA μl LSA 40 μl 2 20 μl LSA 40 μl 4 NC PC LRA MFI Raw Value LS-SA 3 1 NC PC LRA NC LRA SH3002 PC 2 MFI Class I Class II MFI I 10 μl 2 20 μl Class 1 SH3003 Class II SH3003, SH MFI MFI LS-SA LS-SA nmfi 1,000 nmfi 1,000 3,000 SH LRA SH3002 MFI/ LRA LS-SA 4 MFI 2 20 μl 1 10 μl MFI 1 2 FDA 2 2 LSA 33

35 MHC 2019; 26 (1) SH3002 NC LRA 22 HLA-QC LRA LRA 34

36 22 HLA-QC 22 HLA-QC 1)2) 1) 2) 1 FlowPRA, LABScreen, WAKFlow, LIFECODES HLA SH3001 SH LCT 0 AHG-LCT 1 MPHA 3 FCM 0 ICFA 1 LCT, FCM, ICFA SH3002/HLA Class I LCT 4 AHGLCT 0 FCM 7 ICFA 13 Class I 2 Class I+Class II LCT AHG-LCT MPHA FCM FCS ICFA Class I-1 Class I-2 LCT AHG-LCT SH3002 A24 MPHA SH3002 A2 HLA FCM 10,000 ICFA SH3004 A24 1 index LABSceen Single Antigen LS-SA SH3001 LS-SA B*44:02 nmfi 9,944 B*44:02 LS-SA nmfi 35

37 MHC 2019; 26 (1) 2 SH3003 DNA H3003 DNA 27 DNA HLA LS-SA nmfi WAKFlow HR WAK-HR Calmed A*24:02 nmfi 8,551 Calmed 1,915 B*44:03 nmfi 8,108 Calmed 3,376 B*51:02 nmfi 17,679 Calmed 14,970 DRB1*13:02 nmfi 2,648 Calmed 885 DQB1*03:03 nmfi 17,240 Calmed 5, HLA-QC DQA1*03:02 DQB1*03:03 HLA Class II DRB1 DQB1 11 DR9 DRB1*09:01 DQ3 DQ9 DQB1*03:03 LS-SA DQ3 nmfi 10,000 DQB1 DR9 DQ3 DQB DQ DQA1*03:02 DQA1 5 DQA1*03:02 DQA1*03:

38 22 HLA-QC 22 HLA-QC 1)2) 1) 2) 1 6 QCWS ACD-A 7.5 ml 9 21 QCWS HLA SH SH3004 A*24:02 nmfi=14,102 DRB1*09:01 nmfi=19,073 DRB1*12:01 nmfi=17,430 Donor Specific Antibody; DSA FCXM 7 CDC ICFA 4 CDC+FCXM 14 FCXM 10 FCXM+ICFA % CDC-B 75% FCXM ICFA 2 ICFA 5 FCXM 37

39 Major Histocompatibility Complex 2019; 26 (1): 抄録集 TEL TEL

40 17 MHC 2019; 26 (1) 参加費 1 2, , ,000 会議等 会場地図 TEL JR 350 m 39

41 MHC 2019; 26 (1) 17 プログラム HLA 開会の挨拶 オープニングセミナー 44 HLA 一般演題 (1) 1 HLA 1) 2) 1) 1) 1) 1) 1) 2) 2 LABScreen Single Antigen Beads HLA FCM 1) 1) 1) 1) 1)2) 1) 1) 2) 3 HLA Molecular Mismatch Method HLA class II de novo DSA dndsa 4 IgG HLA 1) 1) 2) 3) 3) 1) 3) 3) 3) 1) 1) 1) 1) 2) 3) 40

42 17 MHC 2019; 26 (1) 一般演題 (2) 5 HLA 1) 1) 1) 1) 1)2) 1) 1) 2) 6 MEK 1) 1) 2) 1) 1) 1) 1) 3) 4) 1) 1) 2) 3) 4) 7 HLA-F 1) 2) Daniel E Geraghty 3) 1) 1) 2) Fred Hutchinson Cancer Research Center 3) ランチョンセミナー HLA I HLA II 後援 : 株式会社ベリタス 世話人会 総会 特別講演 HLA Killer immunoglobulin-like receptor KIR 41

43 MHC 2019; 26 (1) シンポジウム (1) 1 HLA 2 HLA HLA 1) 2) 3) 3) 4) 1) 2) HLA 3) 4) 3 HLA 休憩 シンポジウム (2) HLA 1 de novo DSA 1) 2) 1) 1) 1) 1) 2) 2 3 de novo DSA 1) 2) 2) 2) 3) 3) 4) 4) 2) 2) 2) 5) 2) 1) 2) 3) 4) 5) 意見交換会

44 17 MHC 2019; 26 (1) オープニングセミナー 44 HLA 43

45 MHC 2019; 26 (1) HLA ASHI, American Society for Histocompatibility and Immunogenetics 1 NGS Next Generation Sequencing 2 FcRn neonatal Fc receptor FcRn IgG IgG MHC I FcRn ph IgG IgA IgM 5 6 IgG FcRn Rozanolixizumab I 3 CAR-T Chimeric antigen receptor T cell CAR-T T T CAR-T CTL 2017 B ALL 2018 DLBCL FDA 4 CRISPR-Cas9 Clustered Regularly Interspaced Short Palindromic Repeats-Cas9 CRISPR-Cas9 DNA CRISPR-Cas9 PAM Hot topics Best poster Rheumatoid Arthritis, RA HLA- DRB1 71 K E DRB1*04:01 K71E RA 5 Non-HLA AMR Non-HLA MICA alloantibody AT1R, ETAR, Vimentin Autoantibody AT1R AMR nm mrna mirna HLA BOS HLA Collagen-V Col-V 6-2 DNA cell free DNA, cfdna 44

46 17 MHC 2019; 26 (1) DNA ng/ml 160 base pair 2 cfdna AMR 7 UNOS mtilda HLA UNOS API developer.unos.org/ 45

47 MHC 2019; 26 (1) 一般演題 (1) 演題番号 1 ~ 4 46

48 17 MHC 2019; 26 (1) 1 HLA 1) 2) 1) 1) 1) 1) 1) 2) HLA Donor Specific Antibody DSA HLA HLA Cw12 Cw14 B40 DR2 Cw11 DR6Y HLA DSA 47

49 MHC 2019; 26 (1) 17 2 LABScreen Single Antigen Beads HLA FCM 1) 1) 1) 1) 1)2) 1) 1) 2) HLA DSA FCM-XM FCM-XM 382 LABScreen Single Antigen Beads DSA Mean Fluorescence Intensity Mean FI T cell B cell FCM-XM MFI 7 Class I B- cell FCM-XM DSA /FCM-XM 7 FCM-XM MFI Pt/ NC >2 Class II HLA B-cell FCM-XM DSA /FCM-XM DSA / FCM-XM 4 3 FCM-XM Pt/NC >2 Class I DSA MFI T cell FCM-XM MFI R 2 = Class II DSA MFI B cell FCM-XM MFI R 2 = Class I HLA DSA T cell FCM-XM DSA /FCM-XM 7 DSA MFI DSA /FCM-XM LABScreen Single Antigen Beads FCM-XM DSA non-hla 48

50 17 MHC 2019; 26 (1) 3 HLA Molecular Mismatch Method HLA class II de novo DSA dndsa % HLAclass II dndsa HLA-DQ HLA dndsa ABMR DSA ABMR HLA HLA HLA Molecular Mismatch Method HLA HLA class II dndsa ABMR 14 non-abmr 12 2 HLA Cambridge HLA Immunogenicity algorithm EMS HMS Duquesnoy s HLA Structural Model Linear Epitope Conformational Epitope HLA C3d Luminex SAB Immucore HLA Epitope Registry HLA dndsa DSA DSA DSA EMS 31.7vs13.7 HMS 31.1vs12.0 DSA DSA EMS HMS DRB1 DRB3/4/5 DQA1/B1 EMS: 55.5vs21.4 HMS: 57.2vs19.5 P=0.0024, P= HLA dndsa C3d ABMR 36 DSA C3d DSA 30 C3d DSA non-abmr 14 DSA C3d DSA C3d(+)DSA C3d( ) DSA EMS HMS 36.9vs vs21.5 C3d(+)DSA C3d( )DSA P=0.0278, P= HLA 1 HLA class II dndsa 2 HLA-DQ HLA class II 3 DSA 49

51 MHC 2019; 26 (1) 17 4 IgG HLA 1) 1) 2) 3) 3) 1) 3) 3) 3) 1) 1) 1) 1) 2) 3) NAIT NAIT HLA HPA HLA U N HLA A26/33 B61/58 U A2/33 B51/58 N A1/26 B37/ HLA LABScreen Single Antigen OneLambda IgG A1 A2 B37 B51 U N U A2 B51 N A1 B37 A2 B51 A1 IgG A2 B51 A1 IgG1 IgG2 A2 B51 IgG1 IgG2 A1 N A2 B51 IgG3 IgG4 A2 B51 A1 IgG1 IgG2 HLA IgG3 NAIT HLA NAIT 50

52 17 MHC 2019; 26 (1) 一般演題 (2) 演題番号 5 ~ 7 51

53 MHC 2019; 26 (1) 17 5 HLA 1) 1) 1) 1) 1)2) 1) 1) 2) HLA HLA 2 HLA-C*01:02,*08:01 SSP HLA-C*01:02,*08:22 WAKFlow SSOP HLA HLA QCWS

54 17 MHC 2019; 26 (1) 6 MEK 1) 1) 2) 1) 1) 1) 1) 3) 4) 1) 1) 2) 3) 4) 1 MEK mitogen-activated protein kinase T PPARγ MEK Streptozotocin H-2b MHC H-2d 28 MEK PCR T in vitro MEK MEK 30 vs ; p<0.01 MEK 7 T MEK Effector CD4+ T cell 44.0% vs. 58.3%; p=0.03 Naïve CD4+ T cell 42.2% vs. 30.5%; p=0.02 MEK IL-2/IFN-γ MEK 24 viability MEK naïve CD4 T Effector T MEK 53

55 MHC 2019; 26 (1) 17 7 HLA-F 1) 2) Daniel E Geraghty 3) 1) 1) 2) Fred Hutchinson Cancer Research Center 3) HLA-F HLA Ib HLA-F killer immunoglobulin like receptor (KIR)-3DL2 NK HLA-F mrna HLA-F KIR HLA-F HLA-F No.1167 HLA-F HLA-F t-test; p= HLA-F HLA-F HLA-F 54

56 17 MHC 2019; 26 (1) ランチョンセミナー HLA I HLA II 55

57 MHC 2019; 26 (1) 17 HLA 1) 2) 1) 2) HLA HLA HLA One Lambda Inc. 2 HLA HLA HLA Non-HLA LABScan Luminex LABScreen Autoantibody HLA CDC FCXM DSA Donor Specific Antibody FlowDSA- XM HLA A B C DR HLA Class II DP DQ HLA DP DQ 56

58 17 MHC 2019; 26 (1) 世話人会 総会 57

59 MHC 2019; 26 (1) 特別講演 HLA Killer immunoglobulin-like receptor KIR 58

60 17 MHC 2019; 26 (1) Killer immunoglobulin-like receptor KIR Natural killer NK killer immunoglobulin-like receptor KIR HLA KIR HLA NK KIR KIR Ruggeri, Science 2002 HIV AIDS KIR PCR KIR KIR KIR3DL1 HLA-B GD2 Forlenza, J Clin Oncol 2016 Boudreau, J Clin Oncol 2017 KIR KIR3DL1 Ureshino, Shindo, Cancer Immunol Res 2018 KIR KIR KIR 59

61 MHC 2019; 26 (1) シンポジウム (1) 1 HLA 2 HLA HLA 1) 2) 3) 3) 4) 1) 2) HLA 3) 4) 3 HLA 60

62 17 MHC 2019; 26 (1) 1 HLA HLA HLA HLA HLA GVHD T GVHD anti-thymogloblin ATG cyclophosphamide CY HLA GVHD super high risk GVL graft versus leukemia ATG T GVHD / GVL GVHD HLA HLA HLA full allogeneic spousal preliminary data HLA / % ATG 2.5 mg/kg tacrolimus (TAC)+ methylprednisolone (mpsl) 2 mg/kg+short-term MTX (smtx)+mycophenolate mofetil (MMF) 15 mg/kg TAC+mPSL 1 mg/kg HLA 5 62% 31% 61

63 MHC 2019; 26 (1) 17 2 HLA HLA 1) 2) 3) 3) 4) 1) 2) HLA 3) 4) graft-versus-host disease, GVHD graft-versus-leukemia effect GVL GVHD Human leukocyte antigen, HLA HLA-A, -B, -C, -DRB1 HLA 6 HLA HLA HLA- A, -B, -C, -DRB1 HLA GVHD T HLA-A, -B, -C, -DRB HLA HLA-A, -B, -C, -DRB1 8 HLA HLA HLA HLA private haplotype 0.005% 8 90% HLA 90% HLA % % HLA % % % % % % % p= DFS % % % % p= % % % % p= % % % % p= Grade II IV GVHD % % % % p=0.23 Grade III IV GVHD % % % % p=0.54 GVHD

64 17 MHC 2019; 26 (1) 36.8% % % % p=0.60 DFS PS 2 4 HR 2.54, 95%CI , vs PS 0 1 HR 0.81, 95%CI , vs TBI HR 2.21, 95%CI , vs 0 1 DFS HR 1.79, 95%CI: HLA GVHD DFS HLA GVL HLA 63

65 MHC 2019; 26 (1) 17 3 HLA HLA HLA-A, -B, -DRB1 6 2 HLA-A, -B, -C, -DRB /kg CD34 HLA HLA HLA 1 HLA 0 HLA HLA-A, -B, -C, -DRB % 82% 79% P= P= P=0.005 CD34 HLA 2 GVH Homo to hetero HLA 64

66 17 MHC 2019; 26 (1) 休憩 シンポジウム (2) HLA 1 de novo DSA 1) 2) 1) 1) 1) 1) 2) 2 3 de novo DSA 1) 2) 2) 2) 3) 3) 4) 4) 2) 2) 2) 5) 2) 1) 2) 3) 4) 5) 65

67 MHC 2019; 26 (1) 17 1 de novo DSA 1) 2) 1) 1) 1) 1) 2) HLA de novo donor specific HLA antibodies: dn DSA chronic antibody mediated rejection: chronic AMR HLA chronic AMR chronic AMR HLA subclinical HLA chronic AMR HLA 179 Flow PRA screening test LABScreen single antigen test dn DSA dn DSA dn DSA dn DSA % de novo DSA dn DSA 1 4.2% 3 8.5% % dn DSA HLA-class I +class II 7 HLA-DR DR+DQ 7 HLA-DQ chronic AMR 9 T T cell mediated rejection: TCMR +AMR 1 subclinical AMR 3 13 Chronic AMR TCMR+AMR Rituximab Subclinical AMR 4 dn DSA chronic AMR 66

68 17 MHC 2019; 26 (1) 2 CDC T-cell MFI HLA FCM HLA A, B, C, DR, DQ, DP HLA CDC FCM HLA MFI< DSA MFI CDC, FCM DSA B 2 DQ 2 CDC FCM DQ 2 FCM 1 2 AMR 2 HLA HLA A, B, DR FCM 67

69 MHC 2019; 26 (1) 17 3 de novo DSA 1) 2) 2) 2) 3) 3) 4) 4) 2) 2) 2) 5) 2) 1) 2) 3) 4) 5) HLA DSA DSA de novo DSA SAB HLA DSA 17% 38% DSA 50% F2 DSA 3% p=0.001 DSA 41.4% DSA 22.4% p=0.04 DSA DSA 34% DSA 51% DSA p=0.034 DSA p= DSA DSA p= DSA DSA DSA DSA 68

70 Major Histocompatibility Complex 2019; 26 (1): MHC I MHC MHC ES ips 2006 MHC JST J-STAGE MHC II 1 12, Microsoft Word Microsoft Word Microsoft PowerPoint Microsoft PowerPoint CDR 2 1 FAX 69

71 MHC 2019; 26 (1) Susceptibility gene for non-obstructive azoospermia in the HLA class II region: correlations with Y chromosome microdeletion and spermatogenesis. Tetsuya Takao 1), Akira Tsujimura 1), Masaharu Sada 2), Reiko Goto 2), Minoru Koga 3), Yasushi Miyagawa 1), Kiyomi Matsumiya 1), Kazuhiko Yamada 2), Shiro Takahara 1) 1) Department of Urology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan 2) Department of Regenerative Medicine, National Cardiovascular Center, Suita, Osaka, Japan 3) Department of Urology, Osaka Central Hospital, Osaka, Japan FlowPRA HLA 1) 1) 2) 2) 3) 1) 2) 3) cm, ml, g, Kg, pg, μl, %, C HLA-DRB words 5 3 Introduction Materials and Methods Results Discussion Acknowledgements Disclosures References Legend to Figures cm, ml, g, Kg, pg, μl, %, C HLA-DRB words LCT Lymphocyte cytotoxicity test 6 HP coi/index.html COI JSHI_COI COI _ 2 70

72 MHC 2019; 26 (1) Disclosures: none to declare Disclosures: received a reward for lecture from This study was conducted by a research fund from et al. 1. Shi Y, Yoshihara F, Nakahama H, et al.: A novel immunosuppressant FTY720 ameliorates proteinuria and alterations of intrarenal adrenomedullin in rats with autoimmune glomerulonephritis. Regulatory Peptides 127(1 3): , Tongio M, Abbal M, Bignon JD, et al.: ASH#18: HLA-DPB1. Genetic diversity of HLA Functional and Medical Implication (ed. Charron D), Medical and Scientific International Publisher, p , IVIG 1 17(1): 36 40, Medical View p III 1 6, Microsoft Word Microsoft Word Microsoft PowerPoint Microsoft PowerPoint CDR 2 1 FAX words IV 6,000 12,

73 MHC 2019; 26 (1) V J8 MHC tanimoto@att.med.osaka-u.ac.jp Tel: Fax: words 400 words words

74 Major Histocompatibility Complex 2019; 26 (1): Instructions to Authors (updated on Feb. 19, 2019) Submission MHC is the official journal of the Japanese Society for Histocompatibility and Immunogenetics (JSHI). The aim of this journal is to serve as a forum for the scientific information in the form of original and high quality papers in the field of major histocompatibility complex (MHC) and immunogenetics. Manuscripts, from basic to clinical research relating to MHC or immunogenetics, are accepted with the understanding that they are original unpublished work and are not being submitted elsewhere. Manuscripts should be written in Japanese or English. First author and corresponding author must be members of JSHI, while it is preferable for the other co-authors also to be JSHI members. Ethics: Clinical and basic studies using human subjects and specimens obtained from humans must adhere to the 1980 Helsinki Declaration (adapted by the 18 th World Medical Assembly) and must be approved by the ethics review board of each participating institution. Furthermore, animal studies must adhere to such guidelines. Conflict of interest: All the authors must clearly declare any conflicts of interest according to the guideline of JSHI ( Further information is available upon request. Types of papers published: Original articles, reviews, series, short communications (including research and technical bulletins) and case reports are acceptable. Review: The editorial board is responsible for the acceptance of all submitted papers based on a review by multiple referees. Based on the outcome of the review, the board may request corrections, omissions, or additions for publication in MHC. Copyright: Papers that are accepted for publication become copyright of JSHI and will be made available electronically via the J-Stage platform ( Fees: There is no fee for publication. However, authors will be responsible for the costs incurred for color photographs and special prints (please specify at submission if color printing is required). Reprints: Costs incurred for reprints will be charged based on the number of copies and pages (please specify the number of reprints at the time of proofing). 73

75 MHC 2019; 26 (1) Manuscript (in English) 1. Original articles Summary Articles are limited to 4,000 words. Each figure, table, and photograph must be included on separate manuscript pages and must include a title. The location of tables and figures in the manuscript must be clearly stated in the main text. The main text must be submitted as a Microsoft Word file, tables as a Microsoft Word, Excel, or PowerPoint files, and figures and photographs as PowerPoint files. All files must be electronically sent as attached files via to the editor-in-chief. If the authors would like to submit large size files (over 30 MB), the files should be saved on a CD-ROM, which is to be submitted by mail to the editor-in-chief with one printed copies of the manuscript. Alternatively, the large size files may be submitted via a high volume file transfer service. In that case, the authors must contact the editorial office (indicated on the last page of this instruction) before submission. First page The first page is the title page, which must clearly state that the submitted article is an "Original article" and include titles, and the name and affiliation of each author. Include the address, name, telephone number, fax number, and address of corresponding author at the bottom of the title page. Follow the example shown below for the title, author names, and affiliations: Susceptibility gene for non-obstructive azoospermia in the HLA class II region: correlations with Y chromosome microdeletion and spermatogenesis. Tetsuya Takao 1), Akira Tsujimura 1), Masaharu Sada 2), Reiko Goto 2), Minoru Koga 3), Yasushi Miyagawa 1), Kiyomi Matsumiya 1), Kazuhiko Yamada 2), Shiro Takahara 1) 1) Department of Urology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan 2) Department of Regenerative Medicine, National Cardiovascular Center, Suita, Osaka, Japan 3) Department of Urology, Osaka Central Hospital, Osaka, Japan Main text - The second page must contain an "Abstract" no more than 250 words in length, followed by key words (no more than five). 74

76 MHC 2019; 26 (1) - Starting on the third page, the main text begins with the "Introduction" and is followed by the "Materials and Methods", "Results", "Discussion", Acknowledgments, Conflict of Interest, and "References" sections, in this order. - Geographic, human, and scientific names are listed in their original languages. Use generic names for drugs with commercial names in parentheses. - Indicate units and quantities using Arabic numbers followed by international units (cm, ml, g, kg, pg, l, %, C, etc.). References References should include names of authors (last names first); title of article; title of journal (abbreviate according to the style of Index Medicus) or book; volume number; location and name of publishing company (book only); first page, year of publication. For references with more than three authors, list the first three, followed by "et al.". See the examples below: Journal. Shi Y, Yoshihara F, Nakahama H, et al.: A novel immunosuppressant FTY720 ameliorates proteinuria and aiterations of intrarenal adrenomedullin in rats with autoimune glomerulonephritis. Regulatory Peptides 127: , Book. Katz DH: Lymphocyte Differentiation, Recognition, and Regulation. New York, Academic Press, 1997 Chapter in a book. Tongio M, Abbal M, Bignon JD, et al. ASH#18 : HLA-DPB1. Charron D (ed): Genetic diversity of HLA Functional and Medical Implication. Paris, EDK, Short communications (including research and technical bulletins) and Case reports Summary Short communications are limited to 1,500 words. For other information, please see Summary section of Original articles described before. 75

77 MHC 2019; 26 (1) First page The first page is the title page, which must clearly state that the submitted article is a "Short Communication" or "Case report" and include titles and the name and affiliation of each author. Include the address, name, telephone number, fax number, and address of the corresponding author at the bottom of the title page. Follow the example shown below for the title, author names, and affiliations: Main text - Short communications and case reports do not require an abstract. - After the second page, follow the same guidelines for the third and subsequent pages of original articles as described. 3. Reviews, Series, and Others As a general rule, reviews and series are written by invitation from the editorial board; however, submission by JSHI members is strongly encouraged. The editorial board determines the total number of pages, but in general a manuscript of no more than 3,000 words is preferable. As a general rule, reviews and series follow the format for original articles. Editorial Office and Mailing Address Manuscripts should be submitted to the Editor-in-Chief at the Editorial office: Editor-in-Chief: Prof. Akinori Kimura Editorial office: The Japanese Society for Histocompatibility and Immunogenetics Journal, MHC c/o Department of Advanced Technology for Transplantation J8, Faculty of Medicine, Graduate School of Medicine, Osaka University 2-2 Yamadaoka, Suita, Osaka , Japan tanimoto@att.med.osaka-u.ac.jp Tel: Fax:

78 MHC 2019; 26 (1) MHC MHC ips MHC HLA URL URL umin.ac.jp/ jshi@nacos.com Tel Fax hlajimu@m.u-tokyo.ac.jp FAX jshi@nacos.com 77