• No results found

Allogeneic haematopoietic stem cell donation and transplantation across the MHC class I barrier: "Faster is better than more. More is better than less".

N/A
N/A
Protected

Academic year: 2021

Share "Allogeneic haematopoietic stem cell donation and transplantation across the MHC class I barrier: "Faster is better than more. More is better than less"."

Copied!
8
0
0

Bezig met laden.... (Bekijk nu de volledige tekst)

Hele tekst

(1)

Allogeneic haematopoietic stem cell donation and transplantation

across the MHC class I barrier: "Faster is better than more. More is

better than less".

Heemskerk, M.B.A.

Citation

Heemskerk, M. B. A. (2006, September 28). Allogeneic haematopoietic stem cell donation and transplantation across the MHC class I barrier: "Faster is better than more. More is better than less". Retrieved from https://hdl.handle.net/1887/4578

Version: Corrected Publisher’s Version

License: Licence agreement concerning inclusion of doctoral thesis in theInstitutional Repository of the University of Leiden Downloaded from: https://hdl.handle.net/1887/4578

(2)

9

(3)

131 7UDQVSODQWDWLH YDQ EORHGVWDPFHOOHQ DINRPVWLJ YDQ GRQRUHQ LV HHQ JHDFFHSWHHUGH WKHUDSLH YRRUHHQUHHNVYDQEORHG]LHNWHQ+HODDVRQWYDQJHQYHHOSDWLsQWHQGLHKLHUYDQDIKDQNHOLMN]LMQ JHHQWUDQVSODQWDWLH9RRUWUDQVSODQWDWLHYDQEORHGVWDPFHOOHQLVZHHIVHORYHUHHQNRPVWWXVVHQ GRQRUHQSDWLsQWppQYDQGHEHODQJULMNVWHYRRUZDDUGHQYRRUVXFFHV(UZRUGWYRRUDOJHOHWRS GHKXPDQHOHXNRF\WDQWLJHQHQ +/$ +HODDVLVQLHWYRRULHGHUHSDWLsQWHHQ+/$LGHQWLHNH GRQRU EHVFKLNEDDU +HW HHUVWH GHHO YDQ GLW SURHIVFKULIW EHVFKULMIW KHW ]RHNSURFHV QDDU GH JHVFKLNWHVWDPFHOGRQRUGHIDFWRUHQGLHKLHURSLQYORHGKHEEHQHQRSWLHVYRRUYHUEHWHULQJ +HW WZHHGH GHHO EHVFKULMIW PLMQ RQGHU]RHN QDDU +/$YHUVFKLOOHQ GLH ZHO DFFHSWDEHO ]LMQ YRRUWUDQVSODQWDWLH

Transplantatie van bloedstamcellen afkomstig van een donor is een therapie tegen een

JURRW DDQWDO EORHGNDQNHUV ]RDOV OHXNHPLH HQ EORHGVWRRUQLVVHQ ]RDOV HUQVWLJH YRUPHQ YDQ DDQJHERUHQ EORHGDUPRHGH RI HHQ VOHFKW IXQFWLRQHUHQG DIZHHUV\VWHHP 'H]H ]LHNWHV RQWVWDDQ YDDN GRRU HHQ JHQHWLVFKH IRXW LQ GH EORHGVWDPFHOOHQ ZDDUGRRU IRXWHQ RSWUHGHQ LQGHFHOGLIIHUHQWLDWLHGHOLQJHQRIRQWZLNNHOLQJ+LHUGRRUYRUPHQ]HJHHQRIYHUNHHUGH EORHGFHOOHQ$OVHHQJHVFKLNWHGRQRUJHYRQGHQLVNULMJWGHSDWLsQWHHUVWHHQKRRJJHGRVHHUGH FKHPRWKHUDSLHHQRIEHVWUDOLQJVWKHUDSLHRPGHHLJHQEORHGVWDPFHOOHQHQZLWWHEORHGFHOOHQ WHGRGHQ FRQGLWLRQHULQJ 'HZLWWHEORHGFHOOHQ]RDOVGH7FHOOHQHQ%FHOOHQ]LMQHFKWHU HHQ EHODQJULMN RQGHUGHHO YDQ KHW DIZHHUV\VWHHP 'H SDWLsQW LV QD GH FRQGLWLRQHULQJ GDQ RRN ZHHUORRV WHJHQ DOOHUOHL ]LHNWHYHUZHNNHUV ]RDOV YLUXVVHQ EDFWHULsQ HQ VFKLPPHOV 'RRUGDWGHSDWLsQWZHHUORRVLV]LMQ]HLQSRWHQWLHGRGHOLMN'HSDWLsQWZRUGWGDDURPWLMGHQV GH KHOH EHKDQGHOLQJ LQ HHQ VWHULHOH NDPHU RQGHUJHEUDFKW GLH WRWDDO LV JHwVROHHUG YDQ GH EXLWHQZHUHOG

(4)

QLHXZH VWDPFHOOHQ HQ EORHGFHOOHQ 2RN DO LV VWDPFHOWUDQVSODQWDWLH HHQ JHDFFHSWHHUGH EHKDQGHOLQJ KHW LV HHQ ]HHU ]ZDUH WKHUDSLH XLWJHYRHUG ELM SDWLsQWHQ GLH LQ QLHWRSWLPDOH FRQGLWLH]LMQ'HNDQVRSOHYHQVEHGUHLJHQGHFRPSOLFDWLHVHQIDOHQLVJURRW(FKWHU]RQGHU WUDQVSODQWDWLHKHEEHQGH]HSDWLsQWHQKHOHPDDOJHHQNDQVRSRYHUOHYHQ

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sQWHQGRQRU NDQOHLGHQWRWKHYLJHLPPXXQUHDFWLHVRPGDWKHWYUHHPGH+/$NDQOLMNHQRSHLJHQ+/$PHW HHQYUHHPGSHSWLGH

(5)

133 +HODDV ]LMQ +/$LGHQWLHNH GRQRUHQ QLHW JHPDNNHOLMN WH YLQGHQ ,Q 1HGHUODQG KHHIW PDDU ppQ RS GH GULH SDWLsQWHQ HHQ +/$LGHQWLHNH EURHU RI ]XV 'H UHVW LV DIKDQNHOLMN YDQ HHQ WRHYDOOLJ+/$LGHQWLHNIDPLOLHOLGRIHHQJHVFKLNWHQLHWYHUZDQWHGRQRU+HW+/$V\VWHHP KHHIW ELQQHQ GH PHQVHOLMNH SRSXODWLH HHQ JURWH YHUVFKHLGHQKHLG 7HQ HHUVWH ]LMQ HU YRRU VWDPFHOWUDQVSODQWDWLH ]HV JHQHQ EHODQJULMN $OOH ]HV KHEEHQ ]H LQ GH SRSXODWLH HUJ YHHO YHUVFKLOOHQGH YHUVFKLMQLQJVYRUPHQ 9DQ HON JHQ KHHIW GH PHQV HU WZHH ppQ NULMJ MH YDQ MHPRHGHUHQppQNULMJMHYDQMHYDGHU+HWDDQWDOFRPELQDWLHVLVEHSHUNWGRRUGDWDOGH]H JHQHQ RS KHW]HOIGH FKURPRVRRP OLJJHQ HQ JH]DPHQOLMN RYHUHUYHQ (U LV HHQ ZHUHOGZLMG GRQRUUHJLVWUDWLHEHVWDQG PHW GDDULQ WHJHQZRRUGLJ PHHU GDQ WLHQ PLOMRHQ JHUHJLVWUHHUGH VWDPFHOGRQRUHQ'H]HGRQRUHQ]LMQ+/$JHW\SHHUGPDDUQLHWDOWLMGYRRUDOOHJHQHQ9HUGHUH W\SHULQJQDDUJHQQLYHDXJHEHXUWGDQDOVHHQSHUVRRQDOVPRJHOLMNHGRQRUZRUGWDDQJHYUDDJG 9RRUSDWLsQWHQPHWHHQIUHTXHQWYRRUNRPHQGH+/$W\SHULQJ]LMQHUJHQRHJ+/$LGHQWLHNH GRQRUHQPDDUYRRUPHQVHQPHWHHQ]HOG]DDP+/$W\SHLVGLWQLHWKHWJHYDO

Het eerste deel van mijn proefschrift EHVFKULMIW GH UHVXOWDWHQ YDQ GRQRU]RHNWRFKWHQ YRRU1HGHUODQGVHSDWLsQWHQLQGHSHULRGHLQYHUJHOLMNLQJWRWGHSHULRGH (ULVYHUVFKLOJHPDDNWWXVVHQ]RHNWRFKWHQYRRUSDWLsQWHQYDQ1RRUGZHVW(XURSHVH HQDQGHUHKHUNRPVW'HZHUHOGZLMGHGRQRUSRROPHWQLHWYHUZDQWHVWDPFHOGRQRUHQZRUGW QDPHOLMNYRRUDOGRRUGHULMNHZHVWHUVHODQGHQJHYRUPG'HPHHVWHGRQRUHQ]LMQGXVYDQ 1RRUGZHVW(XURSHVH LQFOXVLHIGH9HUHQLJGH6WDWHQYDQ$PHULNDHQ$XVWUDOLs KHUNRPVW'H HWQLVFKHPLQGHUKHGHQLQ1HGHUODQG]LMQPHHVWDODINRPVWLJXLWDUPHODQGHQZDDUSHSHUGXUH VWDPFHOWUDQVSODQWDWLHVHQGRQRUUHJLVWUDWLHEHVWDQGHQJHHQSULRULWHLW]LMQ8LW]RQGHULQJHQ]LMQ ODQGHQDOV-DSDQHQ7DLZDQ9RRUSDWLsQWHQYDQ1RRUGZHVW(XURSHVHKHUNRPVWLVGHNDQV RSHHQGRQRUYHHOJURWHUJHZRUGHQ9RRUVOHFKWVHOISURFHQWYDQGH]HSDWLsQWHQNRQWXVVHQ HQJHHQGRQRUJHYRQGHQZRUGHQ'DDUHQWHJHQZDVYRRUSDWLsQWHQPHWHHQDQGHUH KHUNRPVWLQGHKHOIWYDQGHJHYDOOHQJHHQGRQRUEHVFKLNEDDU +HWYHUJURWHQYDQGHGRQRUSRRORPPHHUSDWLsQWHQHHQNDQVRSWUDQVSODQWDWLHWHJHYHQKHHIW YRRUSDWLsQWHQYDQ1RRUGZHVW(XURSHVHKHUNRPVWZHLQLJ]LQ2PKHWDDQWDOGRQRUHQPHW HHQ]HOG]DDP+/$W\SHVXEVWDQWLHHOWHYHUJURWHQ]RXKHWDDQWDOGRQRUHQQXPLOMRHQ PHHUGDQYHUGXEEHOGPRHWHQZRUGHQ=HHUZDDUVFKLMQOLMNLVGDWQRJQLHWJHQRHJ'HPHHVWH GRQRUHQGLHZRUGHQWRHJHYRHJGKHEEHQQDPHOLMNIUHTXHQWYRRUNRPHQGH+/$W\SHQ9DQ WHYRUHQLVQDPHOLMNQLHWEHNHQGZHONHW\SHULQJHHQGRQRUKHHIW 9RRUSDWLsQWHQYDQ1RRUGZHVW(XURSHVHKHUNRPVWLVHHQDQGHUSUREOHHPYHHOEHODQJULMNHU JHZRUGHQ %LM  ppQ GHUGH YDQ GH SDWLsQWHQ YHUVOHFKWHUW GH NOLQLVFKH FRQGLWLH WLMGHQV KHW GRQRU]RHNSURFHV]RHUJGDWWUDQVSODQWDWLHQLHWPHHUPRJHOLMNLV0HHVWDORYHUOLMGWGHSDWLsQW

(6)

GDQYRRUWUDQVSODQWDWLH'HYHUWUDJLQJELQQHQKHWSURFHVLVRQQRGLJJURRWHQYLQGWRYHUGH KHOHOLQLHYDQKHWSURFHVSODDWVW,GHDOLWHU]RXKHWJHKHOHSURFHVLQ]HVZHNHQNXQQHQZRUGHQ DIJHURQGPDDUWXVVHQHQGXXUGHKHWJHPLGGHOGPHHUGDQYLHUPDDQGHQ9DDNLV HUVSUDNHYDQORJLVWLHNHYHUWUDJLQJ]RDOVELMKHWFRQWDFWHUHQYDQGHGRQRUHQKHWYHUNULMJHQ YDQJRHGHEORHGPRQVWHUVYRRUZHHIVHOW\SHULQJVRQGHU]RHN2RNVSHOHQWUDJHEHVOXLWYRUPLQJ LQGHNOLQLHNHQURQGRPWUDQVSODQWDWLHZDFKWOLMVWHQHHQURO

,Q GLW SURHIVFKULIW LV pp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sQWHQPHWHHQDQGHUHKHUNRPVW'HVOHFKWH ¿QDQFLHOHVLWXDWLHYDQKHWODQGYDQKHUNRPVWVWDDWXLWEUHLGLQJYDQGHGRQRUSRROLQGHZHJ

Het tweede deel van mijn proefschrift beschrijft het onderzoek naar acceptabele

HLA-YHUVFKLOOHQGLHHHQVXFFHVYROOHWUDQVSODQWDWLHQLHWLQGHZHJVWDDQ(U]LMQDOYHUVFKLOOHQGH WKHRULHsQRYHUZDWHHQDFFHSWDEHO+/$YHUVFKLOLV(U]LMQFRPSXWHUSURJUDPPD¶VJHPDDNW RPHHQLPPXXQUHDFWLHWHJHQYUHHPG+/$WHYRRUVSHOOHQ7ZHHKLHUYDQ+/$0DWFKPDNHU HQ+LVWR&KHFN]LMQLQGH]HVWXGLHJHWHVWRSKXQYHUPRJHQRPGH7FHOUHDFWLYLWHLWWHJHQ YUHHPG+/$WHYRRUVSHOOHQ&\WRWR[LVFKH7FHOOHQ]LMQLPPHUVKHWPHHVWYHUDQWZRRUGHOLMN YRRUGHWUDQVSODQWDDWWHJHQJDVWKHHU]LHNWH,QPLMQVWXGLHLVJHNR]HQRPKHWRQGHU]RHNWH ULFKWHQRS+/$NODVVH,YHUVFKLOOHQ'HSDWLsQWGRQRUNRSSHOV]LMQ]RJHVHOHFWHHUGGDW]HppQ +/$NODVVH,YHUVFKLOKHEEHQHQYRRUZDWEHWUHIW+/$NODVVH,,]RYHHOPRJHOLMNRYHUHHQ NRPHQ +/$0DWFKPDNHU HQ +LVWR&KHFN EOLMNHQ QRFK GH7FHO UHDFWLYLWHLW WHJHQ YUHHPG +/$NODVVH,QRFKGHWUDQVSODQWDWLHXLWNRPVWWHNXQQHQYRRUVSHOOHQ

(7)

135 QLHWPHHUKHUNHQEDDU'LWNRPWGRRUGDWHULQKHWOLFKDDPHHQ7FHOVHOHFWLHSURFHVLV(ONH 7FHONDQHQNHOHVSHFL¿HNHSHSWLGHQ DQWLJHQHQ JHSUHVHQWHHUGLQ+/$DOVYUHHPGKHUNHQQHQ 7LMGHQV GH FHOGLIIHUHQWLDWLH YDQ VWDPFHO QDDU 7FHO NULMJHQ GH 7FHOOHQ VSHFL¿HNH +/$ UHFHSWRUPROHFXOHQ2SZLOOHNHXULJHZLM]HNULMJHQYHUVFKLOOHQGH7FHOOHQYHUVFKLOOHQGH+/$ UHFHSWRUHQGRRUGDWNOHLQHPXWDWLHVSODDWVYLQGHQRSJHQHQYRRUGH+/$UHFHSWRUPROHFXOHQ 'H]HJHQHQ]LMQELM]RQGHURPGDW]HHUJJHPDNNHOLMNPXWHUHQ'LWSURFHV]RUJWHUYRRUGDW LHGHUHHQHHQJURWHYHU]DPHOLQJDDQDQWLJHQVSHFL¿HNH7FHOOHQKHHIWGLHHHQHQRUPHUHHNV DDQ]LHNWHVNDQKHUNHQQHQ2PGDWKHWSURFHVZLOOHNHXULJLVRQWVWDDQHUGULHJURHSHQ 7FHOOHQ 7FHOOHQ GLH JHw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ppQH[WUHHPJURRW+/$NODVVH ,YHUVFKLOHHQJURWHUHNDQVRSSDWLsQWRYHUOHYLQJJHHIWGDQppQNOHLQHU+/$NODVVH,YHUVFKLO DOVRRNGH&7/SWHVWQHJDWLHILV,VHHQLGHQWLHNHGRQRUQLHWDDQZH]LJGDQLVGLWHHQJRHG DOWHUQDWLHI

(8)

Referenties

GERELATEERDE DOCUMENTEN

$SSUR[LPDWHO\RQHRXWRIWKUHHSDWLHQWVLQQHHGRIVWHPFHOOWUDQVSODQWDWLRQKDVDVXLWDEOH related donor 1  7KH UHPDLQLQJ SDWLHQWV GHSHQG RQ DOORJHQHLF WUDQVSODQWDWLRQ

+/$0DWFKPDNHU FRQVLGHUV RQO\ WULSOHWV LQ DQWLERG\ DFFHVVLEOH SRVLWLRQV RI WKH +/$ PROHFXOH ZKLFK LV SUREDEO\ WKH PDLQ UHDVRQ WKDW WKH FRUUHODWLRQ ZLWK

The relation between the SSM score of donor/patient couples with a single HLA-A or -B allele mismatch and T cell alloreactivity in vitro (CTLp/10 6 PBL).. The number of pairs in

Figure 1: Number of amino acid differences of single HLA class I incompatibilities versus T cell alloreactivity in vitro (CTLp/106 PBL). Horizontal lines indicate the mean of

Transplanting a single MHC class I mismatched graft from a female donor to a male recipient had significant adverse effect on transplantation outcome independent

127 VHDUFKWLPHVSDQ WREHVXEPLWWHG 7KHPHGLDQWLPHQHHGHGWR¿QGDGRQRUIRUSDWLHQWV RI 1RUWKZHVW (XURSHDQ RULJLQ GHFUHDVHG IURP  PRQWKV WR  PRQWKV DQG

0DUWLQ%DUWKRORPHXV$OH[DQGHU+HHPVNHUNZHUGJHERUHQRSMXQLWH+DDUOHP$DQ KHW 0HQGHO &ROOHJH WH +DDUOHP EHKDDOGH KLM LQ  ]LMQ +$92 GLSORPD HQ LQ

Allogeneic haematopoietic stem cell donation and transplantation across the MHC class I barrier: "Faster is better than more.. More is better