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IgM } HLA T^VI 肖D ア quot
Japanese Journal of Transfusion Medicine, Vol. 52. No. 3 52 (3) #405%413, 2006 ) * IgM } HLA T^V I ÑD±ê"îk¶ÓFDw$ %PTR u§C05OþjU`]_aT^Võ HLA Ñ'¾) Äà í1)3) {e ý2) ±³ Àx1) » ©1) ô+ ù1) ÉÎ hª3) ÐÛ Áø3) ÔÛ Õ1) {ÿ |1) òÞ ó3) ½m ¬1) !Î Èð1) ×!Æ®iWaX$ 1) S_a[Vt¥q¦ 2) ·«Ôsdsñ!ûds 3) (ô¿ 17 å 10 20 ä¨ï) (ô¿ 17 å 12 19 ä¨() HLA T^V I Ñ2±ê"îk¶Ó(platelet transfusion refractoriness#PTR)Cw$9O6 @C=.>E¼Ï4Dù2-O2!IgM }D HLA T^V I Ñ(IgM-HLA Ñ)D PTR FDw $C=.>DùEG@RAB.":6?!PTR u§ 121 ¹DÝ~öÍÂD HLA ÑVT_$Z aUQ!¢¾*Q%.; Mixed passive hemagglutination assay(M-MPHA)û!Flow cytometric reagents for detection of panel-reactive antibody against HLA Class I antigens(FlowPRA)û!Antihuman immunoglobulin lymphocyte cytotoxity test (AHG-LCT) ûCLN.!IgM-HLA ÑD PTR FDw$C=.>E!" 24 ¡vD÷Á±êËn¼(CCI24hours)CLO±ê"p1MºÌ 8;":D~p!M-MPHA ûCLN 121 ´-Ö 48 ´-1M IgM-HLA Ñ2°7P;"fú!FlowPRA ûCLN°?3; IgM-HLA ÑE!:PM 48 -Ö 35 -!AHG-LCT û?E 20 -DI?-< ;"±ê"pE!IgM-HLA ÑQö#9O!48 ´-Ö 7 ´- 74 "C0.>çÙ?3;"IgML)Q£8" HLA ÑDâc¾CÒk9OQ ;B."?E!CCI24hours 2 19.7*4.7(+109! L)Q£8" pQáO6@2?3;2!Òk9OQ ="?E!CCI24hours 2 2.0*1.9(+109! pQáMPB1<;"PTR u§CìÜCÍ9O IgM-HLA ÑE!PTR DgCBO@/M P!:Dè¼bµE AHG-LCT ûCLN°?3B1<;"M-MPHA Q HLA ÑVT_$ZaU! ±ê"DD C%.O6@?!PTR ´-DgrÅ@"pDµC?3Oo æ¾2-O" &!(!'# IgM-HLA Ñ!IgG-HLA Ñ!±ê"îk¶Ó(PTR) !¢¾*¨¸Æy zû(M-MPHA) !FlowPRA $"%# u§2ö#9O HLA T^V I ÑDþjU` °?3O@/MP!H;!Ølék¾?-N1)! Ï4E¤Ñ?-O6@1M4)!±ê"î ]_a(Ig)T^VC=.>E.4=1Dù2- k¶Ó(platelet transfusion refractoriness#PTR) N!IgM }D HLA T^V I Ñ(IgM-HLA Ñ) FDw$ß!,²ÚCE¯&7P>6B1<;" 2 HLA T^V I ÑÊÑD 38'71, Í 9 O :D;JÏ4DÇ?E!HLA ÑVT_$Za "f ë C!IgM-HLA UC8!non-cytotoxic HLA ÑD°D;J ÑE!_a[yüã (LCT)K84E C!LCT ûCn/!Monoclonal antibody-specific \YþjU`]_a&LCT(AHG-LCT)CLN immobilization of platelet antigens(MAIPA)! 6@2ù7P > . O 1) '3) 406 Japanese Journal of Transfusion Medicine, Vol. 52. No. 3 Lymphocyte immunofluorescence test(LIFT)! FlowPRA æLjp%_[bkbm%(FCM# Flow Cytometric Reagents for Detection of Panel- FACSCalibur#Becton Dickinson & Co., Sunny- Reactive antibody against HLA Class I antigens vale!CA)Z¢í>B"Ö§ÃH>F!FITC- (FlowPRA)ÐKÎæZí3FT!IgG K conjugated goat F(ab' ) 2 anti-human IgM(Bio- HLA ]l` I Ã(IgG-HLA Ã)KRZ¯K source!CA#IgM-FlowPRA) H FITC-conjugated Ä´H>!IgM-HLA ÃL¯Ä´H>F3I goat F(ab' ) 2 anti-human IgG(Biosource!CA# 3 " 5) IgG-FlowPRA)Z í 3!IgM-HLA à H IgG- uå!Miller V!Godeaus VL!IgM-HLA à HLA ÃZá$J`]m%eq^>B" K PTR NK ìK{Ù¸Z©>1)2)!QBÑê VL!IgM-HLA-A24 ÃJUX PTR ³öZä >B6)" 2)HPA à HPA-1a!2a!2b!3a!3b!4a!4b!5a!5b! 6a!6b!Naka Zéï>B 12 ®õK O !IgM-HLA Ã7 PTR KvH>F9 ì>F3X{Ù¸H!PTR J ì ? X IgMHLA ÃKÂ97 AHG-LCT æGL¯G8I 3;H7çV6JIDBKGä?X" J K 1!DA 2002 Ø 4 6V 2005 Ø 3 QGK 3 ØG! ÊêÕKtó 6V PTR KvçKB ²ÜZ]pp\q°ñ>!IgM-M-MPHA æ!IgGM-MPHA æJUX`]m%eq^ZDB" 4!HLA F:3@I#HLA-PC$ 10?%7;> 6 IgM-M-MPHA æ!IgG-M-MPHA æ!AHG-LCT æZí3B" 5!L38/%HE ë 24 ¦K CCI(ã¹²ÜÀz·)ÇZ S!rð72DB 121 ³ö(Ƹ 49! ±¸ 72) " §K«JUWSÛÌ>B(CCI24hours) KâÁϺJE3F!HLA Ã!HPA Ã` L)/*ë²Ü·(109! L) ,ë CCI(109! ]m%eq^ZDB" L) + -Ãßè¼(m2) .ë² ¿²Ü·(109! 2!HLA *&,.( Ü·(1011) ¬5UMcd%K HLA ]l` I a[iq^ QB!IgM-HLA Ã7Á >B³öJE3F L!×½Ëbo[5UMª|»bo[Zí3! L!~J=6KPW!ëJí3VYB²Ü LCT æ JUWDB" »(PCs)K HLA H@K PCs JUXë} 7) 3!9C)'-"+.( ZÉO!IgM-HLA ÃKÔs¸JÄw?X 1)HLA à Z¥E PCs 7ë=YB³öK CCI24hours H!Äw 12 ®õK O mqg!²ÜZí3!hb ?XZ¥B I 3 PCs 7 ë = Y B ³ ö K IgM ᨸò£IVMJhb IgG à CCI24hours ZÝÒ>B" ¡¨¸ò£Z¢í?X Mixed passive hemag- 2 glutination assay (IgM-M-MPHA!IgG-M-MPHA) 1!IgM-M-MPHA 5<=FB4%5G / æ8)&10)!FlowPRA æ11)!AHG-LCT æ12)K 4 æ J 37060 àQBL 37090 àK¡µJUW! UWu§`]m%eq^ZDB"QB!u§` 32 ÚQGK HLA-A2 ÃZ¯G8B7! ]m%eq^K}6V!³ö<HJÔs¸ÓÌ 40!220 GL!@YAY 4 Ú!8 ÚQGK JÞîIZ¥EgfnZ¶BJ¾Å>!IgM- HLA-A2 Ã>6¯G8I6DB(Table 1) " M-MPHA æ!IgG-M-MPHA æ!AHG-LCT æ K 2!9C)'-"+.( 3 æJUXÖ§`]m%eq^ZDB" IgM-M-MPHA æ J U W 121 ³ ö È 48 ³ ö IgM-M-MPHA æJ5:X¡xÎH¡¦ (39.71)6V IgM-HLA Ã7¯=Y!@K4 L!AHG-LCT ôy 8 ÚK IgM HLA-A2 ÃZ C 25 ³öGL IgG-M-MPHA æJUW IgG-HLA í3F¤ÍµZÒ!37060 àH>B" ÃT¯=YB(Table 2) ";YV 48 öÈ!IgM- d`_kl z52a z 3 i 407 FlowPRA D H v 3 !IgM-FlowPRA A [ v D 23 s |!AHG-LCT C J L!b C h IgG-FlowPRA AICv 32 !IgG-FlowPRA HLA-A2 1}6N?-<s A22 Oq3 12 s DHv 8 @,><"IgM-FlowPRA @E! C/-?!IgM-M-MPHA O-M5A@!5 IgM-M-MPHA CJLen6N< 48 | 13 NG@}9M5A1@2B0>< HLA hxD D IgM-HLA hx1en@2B0><"cC!IgM- YvO}9M5A1@2<&Table 4' " G<! FlowPRA CJLen6N< 35 D IgM-HLA 5NK 13 sD IgM-M-MPHA CJMv hxE9F?!IgM-M-MPHA CJLen9M \E!s A1 Oq2!dr OQWWPXo9 5A1@2<"Z!AHG-LCT @E!IgM-M- M5ACJLw?[v]7<" MPHA CJLen6N< 48 D.=!20 D IgM-HLA hx70en@2B0><" M-MPHA CJL!IgM-HLA hxA IgG-HLA hx1en6N< 25 s| 13 sC/-?! IgM-M-MPHA G<E IgM-FlowPRA 1 IgM-HLA hxA IgG-HLA hxDYvO:N v!I73E1vDtjO IgM-HLA hx ;N}@2<&Table 5' "IgM-HLA hxA IgG- vA7!IgG-M-MPHA G<E IgG-FlowPRA HLA hxDYv18s1 5 s!Yv1 1v!I73E1vDtjO IgG-HLA w3YBMs1 7 s!Z1YBMs1 1 hxvA9M5ACJLQUS47< HLA s@,><"IgM-HLA hxA IgG-HLA hxD h x v u E!IgM-HLA h x D H v 1 8 Yv18sD{pE 2#3 @,><1! &9+' !IgM-HLA hx(IgG-HLA hxv1 40 YvDYBM s @ E w ? 1 p v @ , > <" &43+' !IgG-HLA hxDHv1 45 &48+' IgM%!IgG-M-MPHA Dw?Dv\E!d @,><&Table 3' " r OQWWPXo9M5ACJL[v]7 IgM-M-MPHA 1v@!IgG-M-MPHA 1 <" 3! %#$" Ta bl e1 Opt i mum c o ndi t i o ns f o r t he I gMMMPHA s c r e e ni ngt e s tus i ngI gM a nt i HLAA2s e r um Se r um t i t r a t i o n Ne ga t i ve Te mpe r a t ur e Mi nut e s c o nt r o l1 :4 1 :8 1 :1 61 :3 2 4 ℃ 2 2 ℃ 3 7 ℃ 3 0 6 0 (-) (-) (-) (-) (-) (-) (W) (-) (-) (-) 3 0 (-) (W) (-) (-) (-) 6 0 (-) (2 +)(W) (-) (-) 3 0 6 0 9 0 (-) (2 +)(W) (-) (-) (-) (2 +)(2 +)(2 +)(W) (-) (2 +)(2 +)(2 +)(W) IgM-M-MPHA CJL!IgM-HLA hxDY v1}@2< 26 s| 7 sD PCs dC/ -?!IgM-HLA hxDYvCy\9Mhf[ v PCs A!y\9Mhfv PCs Ddg^Oe ~@2<&Table 6' "IgM-HLA hxDYvCy \9Mhf[vD PCs @E!CCI24hours 1 19.7)4.7 L' Om7dg^OM5A1@2<1! &*109! IgM-HLA hxDYvCy\9MhfvD L'Om7 PCs @E!CCI24hours 1 2.0)1.9&*109! dg^OKNB0><" h x S Q V $ T X R C J L!IgM-HLA-B5 Cross Reactive Group Antigen&CREG'hxDH Ta bl e2 Co mpa r i s o no fI gMHLA a nt i bo dyde t e c t i o ni n1 2 1s e r as a mpl e sf r o m PTRpa t i e nt s Numbe rde t e c t e dbyo t he rme t ho dsc o mpa r e dt ot heme t ho da tl e f t Me t ho d Numbe r de t e c t e d MMPHA I gM- I gM-& I gG- Fl o wPRA I gG- I gM- I gM-& I gG- I gG- AHGLCT I gMMMPHA 4 8 2 3 2 5 0 3 3 2 8 2 0 I gMFl o wPRA 3 5 1 2 2 3 0 3 3 2 0 1 8 408 Japanese Journal of Transfusion Medicine, Vol. 52. No. 3 Ta bl e3 Summa r yo ft hee s t i ma t e di mmuno gl o bul i nc l a s s e so f9 3HLA a nt i bo di e sde t e c t e di n 1 2 1s e r as a mpl e sf r o m PTRpa t i e nt s I gc l a s so f HLA a nt i bo di e s I gM 8 (9 ) I gM+I gG 4 0 (4 3 ) I gG 4 5 (4 8 ) To t a l 9 3 (1 0 0 ) MMPHA Numbe ro f r e a c t i o npa t t e r ns Numbe r (%) I gM- Fl o wPRA I gG- I gM- I gG- 5 (+) (-) (-) (-) 3 (+) (-) (+) (-) 9 (+) (-) (+) (+) 6 2 2 3 (+) (+) (+) (-) (+) (+) (-) (-) (+) (+) (+) (+) 3 8 7 (-) (-) (+) (-) (-) (-) (+) (+) Ta bl e4 Spe c i f i c i t i e so fI gMHLA a nt i bo di e spo s i t i veo nI gMMPHA a ndne ga t i veo nI gGMMPHA MMPHA Pa t i e ntHLA t ype Pa t i e nt Bl o o d Ge nde r I . D. Type A B Cw A1 A3 O+ B+ M M 2 4 1 1 5 1 5 2 2 5 4 A4 A5 A6 A9 A1 0 A1 1 A1 9 A2 0 A+ A+ A+ O+ A+ A+ B+ A+ F F F F M M F F 2 2 6 2 2 4 1 1 1 2 4 2 A2 1 A2 2 A2 3 A+ O+ B+ F M F 2 2 4 6 1 5 5 2 4 1 1 5 1 5 2 2 2 4 3 5 4 6 2 4 6 1 3 1 3 5 3 5 3 1 4 8 1 1 7 3 3 5 8 2 6 5 2 2 4 5 2 I gM- 1 NT† 9 5 2 1 0 6 2 9 4 4 8 9 5 2 3 5 7 9 5 5 1 1 0 6 2 8 5 4 1 1 1 1 9 8 Fl o wPRA I gG- T‡ NT AHGLCT I gM- I gG- Spe c i f i c i t y * 2 2 0 / 2 0 0 / 2 00 / 2 0(-)(-) 1 0 / 2 0 0 / 2 0 0 / 2 0(-)(-) 0 / 2 0 (Ant i HPA3 b+a nt i HLAA2 ) 0 / 2 0 Ant i HLAB1 3 +B6 0 +B6 1 6 / 2 0 5 / 2 0 8 / 2 0 1 2 / 2 0 1 0 / 2 0 1 2 / 2 0 1 0 / 2 0 5 / 2 0 0 / 2 0 0 / 2 0 0 / 2 0 0 / 2 0 0 / 2 0 0 / 2 0 0 / 2 0 0 / 2 0 0 / 2 0 0 / 2 0 0 / 2 0 0 / 2 0 0 / 2 0 0 / 2 0 0 / 2 0 0 / 2 0 0 / 2 0(-)(-) 0 / 2 0(-)(-) 0 / 2 0(+)(-) 0 / 2 0(-)(+) 0 / 2 0(-)(+) 0 / 2 0(-)(+) 0 / 2 0(+)(+) 0 / 2 0(+)(+) 6 / 2 0 0 / 2 0 0 / 2 0(+)(+) 0 / 2 0 1 0 / 2 0 0 / 2 0 0 / 2 0(+)(+) 1 0 / 2 0 1 0 / 2 0 0 / 2 0 0 / 2 0(+)(+) 0 / 2 0 Ant i HLAA3 1 +A3 3 Ant i HLAB7 +B4 8 +B6 0 Ant i HLAB5 1 +B5 2 Ant i HLACw3 Ant i HLAA2 6 +A3 1 +A3 3 Ant i HLAA2 +B6 0 Ant i HLAB1 3 +B6 0 +B6 1 Ant i HLAB4 8 +B6 0 +B6 1 Ant i HLAA2 6 +A3 3 Ant i HLAA2 Ant i HLAB1 3 +B6 0 +B6 1 †:MMPHA wi t hc hl o r o qui ne unt r e a t e dpl a t e l e t s ‡:MMPHA wi t hc hl o r o qui ne t r e a t e dpl a t e l e t s *:Nu mbe ro fpo s i t i vepa ne l s / Numbe ro ft e s t e dpa ne l s .Yk1E!xX?d2[bgZFie26l| A6 ?,*;!IgG-M-MPHA w= AHG-LCT w. & ' 1!IgM-HLA %*"$)(+#, =B?Qn!IgM-M-MPHA w.znFh26 3 IgM-HLA ]p@YkfqRr?:*; Miller |@ PCs xX<A!*3EB CCI24hours . 0 Fh2 CA!GHJK$MFy*6]IOLNPgZ? xX\S.tCE>-96.!QnFh26 3 | ,*; 4( .cq<)96=v`2;*D.1&! @ PCs x X < A CCI24hours . 4 E 5 E!22.7! aU!T#.y*6 IgM-M-MPHA w<A!uVF L&Fh2xX\SFtCE6 19.6!27.8%'109! ^96 3 j{@Rr@+8!37( ?,*;cBY %Table 7& " kWr._-96"2-2!Ys?y*6 IgMHLA ]p. HLA-A2 ]p 1 j{7/<)D0= -C!1C?om@ IgM-HLA ]pFy*6Ys eklQNKZ[ `52O ` 3 V 409 Ta bl e5 Spe c i f i c i t i e so fI gM-a ndI gGHLA a nt i bo di e spo s i t i veo nI gM-a ndI gGMMPHA Pa t i e ntBl o o d Ge nI . D. Type de r Pa t i e ntHLA t ype A B Cw Sc r e e ni ngme t ho d I gMMMPHA NT† T‡ P/ N* P/ N Spe c i f i c i t i e s I gGMMPHA NT T P/ N P/ N Spe c i f i c i t i e s AHGLCT P/ N Fl o wPRA Spe c i f i c i t i e s I gM I gG B1 0 O+ M 22 46 75 5 17 4 / 1 4 0 / 1 4 B5 1 +B5 2 4 / 1 4 0 / 1 4B5 1 +B5 2 0 / 1 4 (+)(+) B2 2 B+ F 22 43 95 2 7 4 / 1 2 0 / 1 2 A2 6 4 / 1 2 0 / 1 2A2 6 0 / 1 2 (+)(+) B2 5 O+ M 2 41 15 15 2 6 / 1 2 0 / 1 2 A2 6 / 1 2 0 / 1 2A2 0 / 1 2 (-)(+) B7 O+ B1 6 A+ F 2 42 65 26 11 0 F 1 23 76 2 6 6 / 1 2 0 / 1 2 A2 6 / 1 2 0 / 1 2A2 6 / 2 0 0 / 2 0 B4 8 +B6 0 +B6 16 / 2 0 0 / 2 0B4 8 +B6 0 +B6 1 6 / 1 2 A2 (+)(+) 6 / 2 0 B4 8 +B6 0 +B6 1 (+)(+) B1 5 B+ F 2 63 34 46 11 0 4 / 2 0 0 / 2 0 B6 0 6 / 2 0 0 / 2 0B3 5 +B5 1 0 / 2 0 (+)(+) B2 1 B2 3 A+ O+ F F 22 45 25 4 1 4 / 1 6 0 / 1 6 B4 4 22 46 15 5 19 3 / 1 4 0 / 1 4 B6 0 4 / 1 6 0 / 1 6A3 3 4 / 1 4 0 / 1 4B5 1 +B5 2 0 / 1 6 0 / 1 4 (+)(+) (+)(+) B9 B+ F 2 41 15 4 B2 4 O+ F 22 63 96 2 7 7 / 2 0 0 / 2 0 A2 4 B6 O+ F 22 64 46 11 0 8 / 2 0 0 / 2 0 B7 +B4 8 +B6 0 4 / 2 0 0 / 2 0A1 1 1 2 / 2 0 B1 4 B1 9 B+ O+ F F 23 15 13 5 9 22 45 24 6 1 8 / 2 0 0 / 2 0 A2 4 3 / 2 0 0 / 2 0 B5 4 1 4 / 2 0 A2 4 +B4 4 6 / 2 0 B7 +B5 4 1 6 / 2 0 0 / 2 0 B5 1 +B5 2 6 / 2 0 0 / 2 0B1 3 +B6 0 +B6 1 6 / 2 0 B1 3 +B6 0 +B6 1 (+)(+) B1 3 +B6 0 +B6 1 + B1 3 +B6 0 +B6 1 + 1 3 / 2 0 (+)(+) Cw3 Cw3 1 3 / 2 00 / 2 0 6 / 2 0 0 / 2 0B4 4 6 / 2 0 0 / 2 0B7 +B5 4 A1 1 +B7 +B4 8 + (+)(+) B6 0 (-)(+) (+)(+) †:MMPHA wi t hc hl o r o qui ne unt r e a t e dpl a t e l e t s ‡:MMPHA wi t hc hl o r o qui ne t r e a t e dpl a t e l e t s *:Nu mbe ro fpo s i t i vepa ne l s / Numbe ro ft e s t e dpa ne l s Ta bl e6 Re s po ns e (me a n±SD)t opl a t e l e tt r a ns f us i o ni npa t i e nt swi t hI gM HLA a nt i bo di e s t i e ntHLA t ype Pa t i e nt Bl o o d Pa I . D. Gr o up A B Cw Spe c i f i c i t i e so f I gM HLA a nt i bo di e s A3 A4 B+ A+ 2 5 4 1 9 Ant i HLAB1 3+ B6 0+ B6 1 22 46 15 21 0 Ant i HLAA3 1+ A3 3 A5 A+ 2 63 13 56 2 9 4 Ant i HLAB7+ B4 8+ B6 0 A6 B9 B2 3 B2 4 A+ B+ O+ O+ 2 3 54 8 2 41 15 4 22 46 15 5 22 63 96 2 9 Ant i HLAB5 1+ B5 2 1 Ant i HLAB5 1+ B5 2 1 9 Ant i HLAB6 0 7 Ant i HLAA2 4 To t a l PCswi t ho utc o r r e s po ndi ng PCswi t hc o r r e s po ndi nga nt i ge ns a nt i ge ns * CCI 9 Numbe r (×1 0 / L) numbe r 2 4 ho ur s 9 CCI (×1 0 / L) 2 4 ho ur s 6 8 2 2 . 7 ±4 . 3 2 0 . 2 ±2 . 9 2 3 0 1 . 3 ±1 . 9 5 2 5 . 2 ±6 . 1 2 0 . 6 ±0 . 6 2 4 1 5 1 0 6 2 1 . 9 ±4 . 1 1 4 . 2 ±3 . 2 2 4 . 9 ±4 . 1 1 6 . 0 ±3 . 9 6 1 3 8 4 0 . 5 ±1 . 9 0 . 7 ±0 . 5 5 . 4 ±4 . 7 0 . 7 ±1 . 4 7 4 1 9 . 7 ±4 . 7 3 8 2 . 0 ±1 . 9 *:Nu mbe ro ft r a ns f us i o ns +fn;T(CFE" j;dbc;iW0F9'E13#"1*1!IgM- 2!)*%#'"&($ HLA S_R\=)'9> IgM-FlowPRA j:?! IgM-HLA S_?!AHG-LCT j=BDR\:, IgM-M-MPHA j:R\:,5 48 pa 35 p+R E;T(CF9'5+!XM>L^=BD!AHG- \:,56.:&75" LCT j:? IgM-M-MPHA j:R\:,5 48 p HLA HJI I S_> Ig HJIhR\gc=8 a 20 p1*R\2E/;+:,<*75"IgG- ' 9 ?!Miller C1#!Godeau C2#!Laundy C3#= HLA S_R\=)'9? FlowPRA j+YAP BD!IgM S_>@o]+3F4F 28%!46%! c + U -!M-MPHA j ? FCM G m ' 5 LIFT 23%!IgM S_$IgG S_;A=o]+3F4F 410 Japanese Journal of Transfusion Medicine, Vol. 52. No. 3 Ta bl e7 Re s po ns et opl a t e l e tt r a ns f us i o ni npa t i e ntA6wi t hI gMHLAB5 CREGa nt i bo di e s Bl o o d t ype Pa t i e nt Do no r Cr o s s ma t c ht e s t HLAA HLAB HLACw A+ 2 3 5 4 8 9 6 9 0 7 A+ 2 4 3 9 0 A+ 2 2 9 9 4 A+ 9 4 1 7 1 0 9 3 1 1 7 0 8 MMPHA I gM- I gG- AHGLCT CCI 2 4 ho ur s 9 (×1 0 / L) NT† T‡ NT 5 1 4 8 8 (+) (-) (-) (-) 0 5 1 (+) (-) (-) (-) 0 2 5 1 4 8 8 (+) (-) (-) (-) 0 A+ AB+ 2 2 3 5 4 8 8 3 5 9 (-) (-) (-) (-) (-) (-) (-) (-) 2 2 . 7 1 9 . 6 O+ 2 3 5 6 0 9 (-) (-) (-) (-) 2 7 . 8 9 †:MMPHA wi t hc hl o r o qui ne unt r e a t e dpl a t e l e t s ‡:MMPHA wi t hc hl o r o qui ne t r e a t e dpl a t e l e t s 36*!8*!15*!IgG «FKТ1;R<R 0?="ª3FÕE/,AG!HLA «!HPA 28*!46*!62* CÅ7RA,Q"qFp¥ «FÃEVccUdÑ}¼SÎ,Q5C E/,AG!IgM «FKТ1 8 Õ%9*& !IgM GÌÎC.ORQ1!5FN-D¯8,ÕM «'IgG «CMEТ1 40 Õ%43*& !IgG ¨:Q=L!VccUdÑ}¼F»k>4 «FKТ1 45 Õ%48*&B+P!IgM « B HLA «!HPA «FÃS-I2BGD ¸!+Q,G IgG «S¹?= IgM-HLA «1 ,C.ORQ" 52* FÒB~7R="¸F IgM «1 9* IgM-HLA «C IgG-HLA «1CME~ C©FÅE¾ID,FG!IgG-HLA «~ 7R!;R<RF·e¢1¶±B2= 13 ÕE/ E!~t´F, FlowPRA ÆSÎ,=5CE ,A!IgM-HLA «C IgG-HLA «F·e¢1 NQC.ORQ"J= Miller O1&G!HLA V` ¶9Õ!¦3eDQÕ!fÂ1eDQÕF X I «F 7* E IgM'IgA «1¨:Q5C 3 {1¨8="Éj «¤vE/,A!IgM M Å 8 A , Q 1!Ç y E / , A G IgA F «1E¤7R!;F IgG EXT[Z: HLA V`X I «E@,AG~µSn.D0? QF1f½³C.ORA,Q5C0O!! =" IgM-HLA «FÁÄ¢M83G IgG-HLA « }¼SVccUdÑ8AMh¢l8D, HFXT[ZE@,A!Õ6CF|³ÄlS IgG-HLA « F ¨ 1 ® O R A , Q 1!IgM- °-5CEN?A!3 {FE@,A~µSn HLA «E/,AM!}¼SVccUdÑ8 .Q¿Ï1+QC.Q" =E»k1h¢l8D, HLA «1¨8 3! %#$" ="Õ A1 BG!ad_xENQwENP }¼Ë}oFº±G!Ë} 1 u!16$ HPA-3b «1¶±7R!HPA-3b h¢}¼S 24 uF}¼§n¡F¾r S CCI M 8 3 Î,=XVa#]dWENP HLA-A2 «F¨ G*recovery ENP-5C1f½³B+Q14&" 1 ±7R=1!VccUdÑEM HLA- Bishop OG!Ë} 1 uC 20 uF}¼§ A2 «E¬:Q»kGh¢l8D0?=%\# n¡S¾r8!ÓE/,A}¼§n¡Eiz YȲ& "fXVa#]dWE/,AG!Î, SÍ.QÔÏgEGD3!CCI20hours G CCI1hour = 20 _^bF HPA-3b h¢_^b1¦A HLA- FÊ 64*%r(0.67!P)0.001&C Å 8 A , Q A2 ТB+?==L!VccUdÑM 115&!Éjs³ÏgENQ PTR S£83Àm: ¦_^b1Т»kS8! «F¶±1B2D Q=LEG!CCI1hour C CCI24hours Fp¥S-¿Ï ú19 ¶¼ è52 è 3 411 1+T"808ä3HsCDI!HLA-PC E¨.RUT"5HQ-G!'G HLA-PC 9 9¤H¥Ì!ÃH(é!¸H-òÓó 17UTÃG/,CI!CREG ¦Gæ8CO HB;0R!9¡ 1 ÀHÉ"Óáî1©W ¦å1·Ö7UTÍ®1+S!IgM-M-MPHA 0 UC,F,"=H>N!1G/,CI CCI24hours X?,T5ED!Ï> G · Ö 8 I 9 N > IgM- HLH×80©.F0A>"±¡!5z ð HLA ¦åXÇD2T~üÔ1+T" PTR E¨.RUTËFH×! ÝH>NGI! K>!PTR ÃG/,CÇ7U> 48 F H §FTEÊ_ZeEH4ÙFG1#@E¨. IgM-HLA ¦åH-@!øqÔ1öîD2>HI T" 26 FD!¹SH 22 FDIøqÔ1öîD2F ¦ZcY[bZg IgM ¦åI!rÎ5z G/ 0A>"5HQ-G¦åHøqÔ1öîD2F, ,CÆ@F8X>:5E1êRUC/S!Ñ ËFP!ËF A6 HQ-G!ãH/0DIÇD2 àrÎG/,CI!IgM-HLA ¦å1uH¢³ F, HLA ¦åX-:8C,TËFGæ:T PCs »AÔIÚGx<;!M8VnÞDìÖ 9G´8!IgM-M-MPHA 0X¢³»G?, ëHÕ£H~üÔXÁ²8C,TE7. WUC T5ED!5UKD9¤X<áD2F0A> ,T "t/!àrÎG/,CH IgM-HLA ¦ ËFG/,CO!:¤F91D2TE¨.RU å1uH¢³»AÔI!mxX=.T5E T" 16' 1.¯7UC,T17'" ! É"9G/4T IgM-HLA ¦åHEÊðp # IgM-HLA ¦å1 PTR ÃH 52* Gâµ8! GB,CI!Godeau R1!50 ÐHÉ"9 IgG-HLA ¦åEö>G PTR HuGFT~üÔ ÃGB,C!prospective G HLA ¦åH·ÖX 1+T5E1Á²7U>"IgM-HLA ¦åHÿÓ ×8>!PTR JHxGB,CI§FTõ oÌ1 AHG-LCT 0DIÇD2F0A>5E 1#@D+TE.¯8C,T2'"K>!Miller R 0R!IgM-M-MPHA X HLA ¦å!HPA ¦å`\ I!ئåö>G!í}!|ÔH HLA ¦åI j$fl]!É"9H´H¢³»G?,T EÊðGp21F,~üÔ1+TE8F1RO! 5ED!PTR ËFHu×E9¤H¥ÌG IgM-HLA ¦åHL1Ç7U> 4 ËFG/,C ªD2T~üÔ1+T" PTR 1âµ8>5E0R!IgM-HLA ¦å1 PTR ÄÂ#H)H6¬{X½SK8>ikhklØž G=8C,T~üÔO+S!§FTõ1#@ yalb$H Linda Cantwell ÛÖ!HLA ñ®É"9 D+TE^ild8C,T1'"W1°G/,CI G´8!9¤HþîG6D3?7,K8>ì7ù ô7R1!IgM-HLA-A24 ¦åGQT PTR ËFX 13 &vHÛÖ/GÄ,>8K:" ç,KUFËFE8C.¯8C,T1 !±H 6' ×GQS!9¤1õD2> IgM-HLA ¦ åX¿B 7 ËFÞCG/,C9¤1÷RUF 0A>5E0R!IgM-HLA ¦åIä3HËFG /,C PTR HuEFT~üÔ1¬," L'D!$È+³1(4.7 CCI24hours 1 5.4&)109! Eç2,ËF B23 DI!Ã1 IgG-HLA ¦åX :8C , > 5 E 0 R! à H HLA-B61 ¦ H CREG ¦D+T HLA-B60 H HLA-PC 197 U!I9NH 4 I9¤1÷RU>"808! 5 6o«H HLA-B60 H HLA-PC DI9¤ X÷T5E1D2F0A>&c$b3ïÁ' "5U I!Ï>G IgM-HLA-B60 ¦å1·Ö7U>>N è 53 ßÒÜH)&1H)H@ºI*Õ 17 û 5 28 ú!è 53 ú19 ß&wn'Dý%8>" ' $ " 1'Miller K, Kickler TS, Ness PM, et al#Immunoglobulin class heterogeneity of platelet antibodies. Vox Sang, 47#421%426, 1984. 2'Godeau B, Fromont P, Seror T, et al#Platelet alloimmunization after multiple transfusions # a prospective study of 50 patients. Br J Haematol, 81#395%400, 1992. 3'Laundy GJ, Bradley BA, Rees BM, et al#Incidence and specificity of HLA antibodies in multitransfused patients with acquired aplastic anemia. Transfusion, 44#814%825, 2004. 4'Iwaki Y, Lau M, Terasaki PI#Successful trans- 412 plants across T warm-positive cross-matches due to IgM antibodies. Clin Transplant, 2$81% 84, 1988. 5'International forum$Detection of platelet-reactive antibodies in patients who are refractory to platelet transfusions, and the selection of compatible donors. Vox Sang, 84$73%88, 2003. 6'rMQ!~K u!lA\B!m$anti-PLT# 9@=9#MPHA .O[.*0( IgM <8 > HLA Po156N^tNyDa&`' "s NGEV!50$296, 2004. 7'Terasaki PI, McClelland JB$Microdroplet assay of human serum cytotoxins. Nature, 204$998% 1000, 1964. 8'Ohgama J, Yabe R, Tamai T, et al$A new solidphase assay system using magnetic force on blood group serology. Transfusion Medicine, 6$ 351%359, 1996. 9'cp_X!Ab d!ipJT!m$Yf T7 S,-ek0N^tPoO[2U4"NCW L!25$33%40, 2002. 10'Tamai T, Ishii Y, Mazda T$IgM alloantibody detection by M-MPHA , a new solid-phase assay system. Transfusion Science, 23$47%54, 2000. 11'Pei R, Wang G, Tarsitani C, et al$Simultaneous Japanese Journal of Transfusion Medicine, Vol. 52. No. 3 HLA class I and class II antibodies screening with flow cytometry. Hum Immunol, 59$313% 322, 1998. 12'Johnson AH, Rossen RD, Butler WB$Detection of alloantibodies using a sensitive antiglobulin microcytotoxicity test. Tissue Antigens, 2$215% 226, 1972. 13'hr x!npg{!]Rjw!m$P HLA :? ; I Po2|}zO[Iq/N^tNHZ1 )+6|}zPoO[%AHG-LCT!LIFT! PIFT!M-MPHA )53 FlowPRA 2vF"s NEV!50&6' $753%760, 2004. 14'Novotny VMJ$Prevention and management of platelet transfusion refractoriness . Vox Sang , 76$1%13, 1999. 15'Bishop JF, Matthews JP, McGrath K, et al$Factors influencing 20-hour increments after platelet transfusion. Transfusion, 31$392%396, 1991. 16'McCalmon RT Jr, Tardif GN, Sheehan MA , et al$IgM antibodies in renal transplantation. Clin Transplant, 11$558%564, 1997. 17'Katz SM, Kimball PM, Ozaki C, et al$Positive pretransplant crossmatches predict early graft loss in liver allograft recipients. Transplantation, 57$616%620, 1994. 345.,+01 252- 2 3 / 413 PLATELET TRANSFUSION REFRACTORINESS ASSOCIATED WITH IGM-HLA-CLASS I ANTIBODIES $IMMUNOGLOBULIN CLASS HETEROGENEITY OF HLA CLASS I ANTIBODIES IN PTR PATIENTS Satoshi Saito1'3', Toyohiro Tamai2', Masao Ota3', Satoshi Ota1', Masayoshi Komatsu1', Morito Hirabayashi1', Keiko Tamaki1', Hideyuki Seshimo1', Hisashi Shimizu1', Hideki Asamura3', Hirofumi Fukushima3'and Setsuo Nomura1' 1' Japanese Red Cross Nagano Blood Center Diagnostic Systems Department, Olympus Corporation 3' Department of Legal Medicine, Shinshu University School of Medicine 2' Although HLA-class I antibodies&Abs'are considered one of the major obstacles in posttransfusion platelet increments for platelet transfusion refractory&PTR'patients, whether IgM-HLA-class I Abs are associated with accelerated platelet destruction and transfusion failure remains unclear. Accordingly, we assessed the frequency of IgM-HLA-class I Abs development in 121 PTR patients using the magnetic-mixed passive hemagglutination assay&M-MPHA' , flow cytometric reagents for detection of panel-reactive antibody against HLA Class I antigens&FlowPRA'and the anti-human immunoglobulin lymphocyte cytotoxity test&AHG-LCT'. The relationship between IgM-HLA-class I Abs and PTR was assessed by calculating 24 h post-transfusion corrected platelet count increments . Result showed that IgM-HLA-class I Abs were detected in 48 of 121 patients using the M&CCI24hours' MPHA. Only 20 and 35 of these 48 IgM-HLA-class I Abs were detected using the AHG-LCT and FlowPRA respectively. In 7 of 48 patients positive for IgM-HLA-class I Abs, 74 transfusions without L' "In corresponding antigen for specificities of IgM-HLA-class I Abs had CCI24hours of 19.7(4.7&)109! contrast, 38 transfusions with corresponding antigens for specificities of the same Abs had CCI24hours of 2.0(1.9&)109 !L'. Collectively, IgM-HLA-class I Abs were detected in 39.7* of PTR patients, and were considered to play a role in mediating refractoriness to platelet transfusions. In 28 of 48 cases, IgM-HLA-class I Abs could not be detected by the AHG-LCT. Detection of IgM-HLA-class I Abs using the M-MPHA may clarify the as yet unknown mechanism of the pathogenesis of PTR. Key words# IgM-HLA-class I antibodies, IgG-HLA-class I antibodies, Platelet transfusion refractoriness&PTR', Magnetic%mixed passive hemagglutination assay&M-MPHA'!Flow Cytometric Reagents for Detection of Panel-reactive antibody against HLA Class I antigens &FlowPRA'