complement system

ȯºîÀ­Ìë´Ö¥Ø¥â¥°¥í¥Ó¥óÇ¢¾É paroxysmal nocturnal hemoglobinuria-PNH

PIGA(phosphatidylinositol glycan anchor biosynthesis class A)°äÅÁ»Ò¤¬·ç»¤·¤¿Ã±ÆÈ¤¢¤ë¤¤¤ÏÊ£¿ô¤Î¤·ì´´ºÙ˦¥¯¥í¡¼¥ó³ÈÂç¤Ë¤è¤ë¸åÅ·À­Â¤·ì´´ºÙ˦¼À´µ.*1

PIGA°äÅÁ»Ò>NCBI gene page

Xp22.2 7exons

¤³¤Î°äÅÁ»Ò¤Ï GPI¥¢¥ó¥«¡¼¹çÀ®·ÐÏ©¤ÎºÇ½é¤ÎÃæ´ÖÂΤǤ¢¤ë,N-acetylglucosaminyl phosphatidylinositol (GlcNAc-PI)¤Î¹çÀ®¤ËɬÍפʥ¿¥ó¥Ñ¥¯¤ò¥³¡¼¥É¤¹¤ë. GPI anchor¤Ï¿¤¯¤Î·ìµåɽÌ̤˥¢¥ó¥«¡¼¥¿¥ó¥Ñ¥¯¼Á¤ò¶¡µë¤¹¤ëÅü»é¼Á.

  • PNH¤Ç¤Ï¤·ì´´ºÙ˦¥ì¥Ù¥ë¤ÇPIGA°äÅÁ»Ò¤¬ÊѰۤ·GIP anchorÀ¸¹çÀ®¤ÎºÇ½é¤Î¥¹¥Æ¥Ã¥×¤¬¤«¤é¾ã³²¤¬¤ª¤³¤ê, ¤¹¤Ù¤Æ¤ÎGIP¥¢¥ó¥«¡¼¥¿¥ó¥Ñ¥¯(GPI-AP)¤¬È¯¸½Äã²¼¤¢¤ë¤¤¤Ï·ç»¤·¤Æ¤¤¤ë.
  • PNH¤Î·ìµå¤Ç¤Ï, decay accelerate factor(DAF), CD59¤À¤±¤Ç¤Ï¤Ê¤¯, ¹¥Ãæµå¥¢¥ë¥«¥ê¥Õ¥©¥¹¥Õ¥¡¥¿¡¼¥¼, ÀÖ·ìµå¥¢¥»¥Á¥ë¥³¥ê¥ó¥¨¥¹¥Æ¥é¡¼¥¼¤Ê¤É20¿ô¼ïÎà¤ÎGPI-AP¤Î·ç»¤¬Êó¹ð¤µ¤ì¤Æ¤¤¤ë.
     
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PNH¤Ë¤ª¤¤¤ÆÌë´Ö¤ÎÍÏ·ì¤Ë¤è¤ë¡ÖȯºîÀ­¡×ÁáÄ«¥Ø¥â¥°¥í¥Ó¥óÇ¢¤ò¤­¤¿¤¹¤Î¤Ï1/4¡Á1/3¤Ç¤¢¤ê, ´ðËÜÉÂÂÖ¤ÏËýÀ­·ì´ÉÆâÍÏ·ì¤Ç¤¢¤ë.

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  • Ham»î¸³(»ÀÀ­²½·ìÀ¶»î¸³):·ìÀ¶¤òpH6.5-7.0¤Ë»ÀÀ­²½¤¹¤ë¤³¤È¤ÇÊäÂηϤ¬³èÀ­²½¤µ¤ì¤ë¤³¤È¤òÍøÍѤ·¤¿ÊäÂδ¶¼õÀ­ÀÖ·ìµå¤Î¸¡½ÐË¡.
  • ¥·¥çÅü¿å(º½Åü¿å)»î¸³:¥¤¥ª¥ó¶¯ÅÙÄã²¼¤Î¾ò·ï²¼¤ÇÊäÂηϤò³èÀ­²½¤·ÊäÂδ¶¼õÀ­ÀÖ·ìµå¤Î¸¡½Ð¤ò¤ª¤³¤Ê¤¦.
  • ·ì´ÉÆâÍÏ·ì¤Î»ØÉ¸¤Ë¤ÏLDH¤ÎÃͤò¤ß¤ë. PNHÀÖ·ìµå¥¯¥í¡¼¥ó¤¬3-5¡ó°Ê¾å¤Ç¤¢¤ì¤ÐÍϷ줬¤ª¤³¤ê, LDH¤Ï´ð½àÃ;å¸Â¤Î1.5Çܰʾå¤Î°Û¾ïÃͤò¼¨¤¹.(PNHÇò·ìµå¤Ï23%°Ê¾å¤ÇLDH¤¬¾å¾º¤¹¤ë. Çò·ìµå¤¬ÀÖ·ìµå¤è¤ê¿¤¤¤Î¤ÏÍ¢·ì¤ò¼õ¤±¤ë´µ¼Ô¤µ¤ó¤¬Â¿¤¤, ÀÖ·ìµå¼÷Ì¿¤¬Ä¹¤¤, ÀÖ·ìµå¤¬ÊäÂΤˤè¤ëÇ˲õ¤òÇò·ìµå¤è¤ê¤â¼õ¤±¤ä¤¹¤¤¤«¤é¤È¹Í¤¨¤é¤ì¤ë.)*2 ¡£Â¾¤Ë·ìÀ¶Í·Î¥Hb, ¥Ø¥â¥°¥í¥Ó¥óÇ¢, ·ìÀ¶¥Ï¥×¥È¥°¥í¥Ó¥óÄãÃͤÏLDH¤Î¾å¾º¤È¤È¤â¤Ë, ·ì´ÉÆâÍÏ·ì¤ò¼¨º¶¤¹¤ë¡£
  • ÍÏ·ì½ê¸«¤ò³Îǧ¸å, ¹â´¶ÅÙFCMË¡: FCM¤Ë¤è¤êCD55-, CD59-, ÀÖ·ìµå/Çò·ìµå¤ò¸¡½Ð, ¤Þ¤¿¤ÏFLARE¤Ë¤è¤ê¸¡½Ð¤¹¤ë-¤Ë¤è¤ê1¡ó°Ê¾å¤ÎPNH¥¿¥¤¥×ÀÖ·ìµå¤ò¸¡½Ð¤¹¤ë¡£

PNHÀè¹Ô¿ïȼÉÂÊÑ

  • PNH¤Ç¤Ï, anaplastic anemia(AA)¤¢¤ë¤¤¤Ï, MDS¤òÀè¹ÔÉÂÊѤȤ·¤Æ¿ïȼ¤¹¤ë¤³¤È¤¬¤¢¤ë.¡¡AA¤òȼ¤¦ÉÑÅÙ¤ÏÆüËܤǤÏ37.8%¤È¥¢¥á¥ê¥«¤Î29.0%¤è¤ê¤â¹âÉÑÅ٤Ǥ¢¤ë. MDS¤Î¿ïȼÉÑÅÙ¤Ï5%Á°¸å¤Çº¹¤¬¤Ê¤¤. *3
  • PNH·¿·ìµå¤¬¹â´¶ÅÙFCM¤ÇÍÛÀ­¤ÎAA¤Ï¡¢ÌȱÖÍÞÀ©ÎÅË¡¤Ë´¶¼õÀ­¤¬¹â¤¯Í½¸å¤¬Îɤ¤¤³¤È¤¬ÃΤé¤ì¤Æ¤¤¤ë.*4
     
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FLAER

PNH¤Îflowcytometry¸¡ºº¤Ç, ºÙ˦ɽÌ̾å¤ÎGPI¥¢¥ó¥«¡¼·¿¥¿¥ó¥Ñ¥¯¼Á¤Î¥¢¥ó¥«¡¼Éô¤ËÆÃ°ÛŪ¤Ë·ë¹ç¤¹¤ë°äÅÁ»ÒÁȤߴ¹¤¨¥¢¥¨¥í¥ê¥¸¥ó¤È¤¤¤¦·Ö¸÷ºÙ¶Ý¥¿¥ó¥Ñ¥¯¥Õ¥ì¥¢(fluorescent-labeled inactive toxin aerolysin; FLAER)¤ò»È¤Ã¤ÆPNH·ìµå¤ò¸¡½Ð¤¹¤ë¿·¤·¤¤ÊýË¡¤¬ÍѤ¤¤é¤ì¤Æ¤¤¤ë¡£FLAER¤ÏÀÖ·ìµå¤ò¶Å½¸¤µ¤»¤ë¤¿¤á¤Ë, ÀÖ·ìµå²òÀϤˤϻÈÍѤǤ­¤Ê¤¤¤³¤È¤¬·çÅÀ¡£

CD55/ CD59

Àµ¾ïºÙ˦¤Ç¤ÏCD55, CD59¤¬¤È¤â¤ËÍÛÀ­. PNH¾ÉÎã·ìµå¤Ç¤ÏCD55-, CD59-¥¯¥í¡¼¥ó¤¬½Ð¸½¤¹¤ë¡£ÄøÅ٤ϾÉÎã¤Ë¤è¤ê¤µ¤Þ¤¶¤Þ¤Ç1¡Á99%. 0.01%ÄøÅÙ¤ÎPNH·ìµå¤ò¸¡½Ð¤Ç¤­¤ë¹âÀºÅÙFCM¤¬ÍѤ¤¤é¤ì¤ë. ðùγµå¤ËÂФ·¤Æ¤Ï¾åµ­FLAER¤òÍѤ¤¤¿¸¡ºº¤¬¿ä¾©¤µ¤ì¤Æ¤¤¤ë.

CD55, CD59¤¤¤º¤ì¤â, ·ì±ÕºÙ˦¤ÎGPI-anchor(glycosyl-phosphatidylinositol anchor)¤ÎÉôʬ¤ÇËì¤Ë·ë¹ç¤·¤Æ¤¤¤ëGPI Ëì·ë¹çÃÁÇò¤Ç, ÊäÂγèÀ­²½¤òÍÞÀ©¤¹¤ëÊäÂÎÄ´À᥿¥ó¥Ñ¥¯¼Á. CD59¤¬ÊäÂΤˤè¤ëÍÏ·ìÁ˻ߤˤè¤ê½ÅÍפȹͤ¨¤é¤ì¤Æ¤¤¤ë.

  • CD59, CD55¤ÈÊäÂηϤΥڡ¼¥¸¤Ë°Üư-->CD55, CD59

PNH¤Î¼£ÎÅ-¹³ÊäÂÎÌô¤ÎÅоì

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¥¨¥¯¥ê¥º¥Þ¥Öeculizumab¤Ï, PNH¤ËÍ­¸ú¤Ê¹³C5¹³ÂÎÌô¤È¤·¤Æ³«È¯¤µ¤ì¤¿.2007ǯ¤Ë³«»Ï¤µ¤ì¤¿AEGIS»î¸³¤Ë¤è¤ê°ÂÁ´À­¡¦¸ú²Ì¤¬³Îǧ¤µ¤ì2011ǯ¤ËÌô²Á¼ýºÜ.

¥¨¥¯¥ê¥º¥Þ¥Ö¤ÏÊäÂÎC5¤Îepitope¤È·ë¹ç¤·±ê¾ÉÀ­¥¿¥ó¥Ñ¥¯¤Ç¤¢¤ëC5a(¥¢¥Ê¥Õ¥£¥é¥È¥­¥·¥ó)Êü½Ð¤òÁ˳²¤¹¤ë¤È¤È¤â¤Ë, C5ž´¹¹ÚÁǤκîÍѤòÁ˳²¤·, ¤³¤ì¤Ë³¤¯C5b-C9Ë쿯½±Ê£¹çÂÎ(MAC)¤ÎÀ¸À®¤ò¤µ¤»¤Ê¤¤. ɸ¶ÂÎ¥ª¥×¥½¥Ë¥ó²½¤äÌȱÖÊ£¹çÂνüµî¤Ë¤Ï±Æ¶Á¤ò¤¢¤¿¤¨¤Ê¤¤¤¿¤á, ½ÅÍפÊÊäÂε¡Ç½¤ÏÊÝ»ý¤µ¤ì¤ë.

¥¨¥¯¥ê¥º¥Þ¥ÖÅêÍ¿¤ÇPNHÀÖ·ìµå¤ÏÁý²Ã¤¹¤ë(²õ¤ì¤Ê¤¤).LDH¤Ï¸º¾¯¤··ì´ÉÆâÍÏ·ì¤ÏÍÞÀ©¤µ¤ì¤ë¡£¤·¤«¤·CD55¤¬·ç»¤·¤Æ¤¤¤ë¤¿¤áC3b¤È¤½¤Îʬ²ò»ºÊª¤Ç¤¢¤ëC3d, C3dg¤¬PNHÀÖ·ìµå¾å¤ËÃßÀѤ·, ·ì´É³°ÍϷ줬¸²ºß²½¤·¤Æ¤¯¤ë.
´µ¼Ô¤µ¤ó¤ÎLDH¤ÏÃøÌÀ¤Ë¸º¾¯¤¹¤ë¤Î¤ËÉÏ·ì²þÁ±¤¬»×¤ï¤·¤¯¤Ê¤¤, ²«áÕ¤¬»ý³¤¹¤ë¤Î¤Ï¤³¤Î·ì´É³°ÍÏ·ì¤Ë¤è¤ë¤â¤Î¤È¹Í¤¨¤é¤ì¤ë.ľÀÜCoombs¥Æ¥¹¥È¤ÏÍÛÀ­¤È¤Ê¤é¤Ê¤¤¤¬, FCM¤òÍѤ¤¤ë¤ÈC3À®Ê¬¤ÎÃßÀѤ¬¸¡½Ð¤µ¤ì¤ë.*5

ÊäÂΤΥڡ¼¥¸¤ò¸«¤ë--->ÊäÂÎ ¥¯¥ê¥Ã¥¯¤Ç´ØÏ¢¥Ú¡¼¥¸¤Ë°Üư


*1  Takeda J, et al. Deficiency of the GPI anchor caused by a somatic mutation of the PIG-A gene in paroxysmal nocturnal hemoglobinuria. Cell 73:703-711, 1993
*2  Pu JJ, et al. Natural history of paroxysmal nocturnal hemoglobinuria clones in patients presenting as aplastic anemia. Eur J Haematol. 2011 Jul;87(1):37-45.
*3  À¾Â¼½ã°ì,¶âÁÒ ¾ù¡§È¯ºîÀ­Ìë´Ö¥Ø¥â¥°¥í¥Ó¥óÇ¢¾É. Æñ¼£À­ÉÏ·ì¤Î¿ÇÎÅ¥¬¥¤¥É¡ÖÆñ¼£À­ÉÏ·ì¤Î¿ÇÎÅ¥¬¥¤¥É¡×ÊÔ½¸°Ñ°÷²ñÊÔ, P93-130,Æî¹¾, Åìµþ, 2011
*4  Hillmen P, et al.Effect of eculizumab on hemolysis and transfusion requirements in patients with paroxysmal nocturnal hemoglobinuria.N Engl J Med. 2004 Feb 5;350(6):552-9.
*5  Risitano AM,et al.Complement fraction 3 binding on erythrocytes as additional mechanism of disease in paroxysmal nocturnal hemoglobinuria patients treated by eculizumab.Blood. 2009 Apr 23;113(17):4094-100.

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Last-modified: 2021-02-14 (Æü) 12:10:36 (19d)