㼀㼍㼎㼘㼑㻌 㻞㻌 㻌 㻭㻰㻭 㑇ఏᏊኚ␗య䛾㓝⣲άᛶ ƌƌ ĞĚŽŶĚŽͲs Ğ ŐĂ & y Ğƚ Ăů͘ŵ:,Ƶŵ 'ĞŶĞƚ͘ϭϵϵϴ͘

資 料

デ⒪࢞࢖ࢻࣛ࢖ࣥ

ADA Ḟᦆ⑕

a) ⑌ᝈᴫせ

• ࢔ࢹࣀࢩࣥࢹ࢔࣑ࢼ࣮ࢮ(ADA)ࢆࢥ࣮ࢻࡍࡿ ADA 㑇ఏᏊ㸦20q13.11㸧ࡢ␗ᖖ࡟

㉳ᅉࡍࡿཎⓎᛶච␿୙඲⑕

• ADA 㓝⣲άᛶࡢḞᦆࡲࡓࡣపୗ࡟ࡼࡾ, ࡑࡢᇶ㉁࡛࠶ࡿ࢔ࢹࣀࢩࣥ, ࢹ࢜࢟ࢩ

࢔ࢹࣀࢩࣥࡀ⣽⬊ෆ࡟⵳✚ࡋ, ᚋ⪅ࡢࣜࣥ㓟໬⏘≀(dAXP)ࡀ✀ࠎࡢ⣽⬊ࡢᶵ⬟

ࢆ㞀ᐖࡋ, ከᙬ࡞⮫ᗋ⑕≧ࢆᘬࡁ㉳ࡇࡍࠋ

• ࡑࡢከࡃࡣ㔜⑕」ྜච␿୙඲⑕ (SCID) ࢆ࿊ࡋ (ADA-SCID) , ᪩ᮇ࡟㐺ษ࡞

἞⒪ࢆ⾜ࢃ࡞࠸࡜⮴Ṛⓗ࡞ឤᰁ࡛Ṛஸࡍࡿࠋ

• 1ࠥ10 ṓ࡛Ⓨ⑕ࡍࡿ㐜Ⓨᆺ (Delayed onset)ࡸ 10 ṓ௨㝆࡟ Ⓨ⑕ࡍࡿᬌⓎᆺ

(Late onset) ࡶᏑᅾࡋ, ឤᰁ⑕ࡣSCID࡟ẚ࡭࡚㍍⑕ࡔࡀ, ⁐⾑ᛶ㈋⾑ࡸ⾑ᑠᯈῶ

ᑡ࡞࡝ࡢ⮬ᕫච␿⑌ᝈࡸ⫵⑓ኚࢆ࿊ࡍࡿࡇ࡜ࡀከ࠸ࠋ b) ␿Ꮫ

• SCIDࡣ40,000ࠥ75,000ே࡟1ேࡢ㢖ᗘ࡛ฟ⏕ࡍࡿࠋᖖᰁⰍయຎᛶ㑇ఏᙧᘧࢆ࡜

ࡾ, ᮏ㑥࡛ࡣADA-SCIDࡣSCIDࡢ⣙15%ࢆ༨ࡵ, X㐃㙐SCID (XSCID)࡟ࡘ࠸࡛

2␒┠࡟ከ࠸ࠋ

• ⏕ᚋᩘࣨ᭶௨ෆ࡟㔜⑕ឤᰁࢆⓎ⑕ࡍࡿ౛ࡀከࡃ, ཎᅉ୙᫂ࡢṚஸ౛ࡢ࡞࠿࡟ࡶ

Ꮡᅾࡋ࡚࠸ࡿྍ⬟ᛶࡀ࠶ࡿࠋ c) デ᩿ࡢᡭᘬࡁ

• ⮫ᗋ⑕≧㸸

– ࢘࢖ࣝࢫឤᰁ⑕: ࢧ࢖ࢺ࣓࢞ࣟ࢘࢖ࣝࢫ, Ỉ①࢘࢖ࣝࢫ, RS ࢘࢖ࣝࢫ࡞

࡝ࠋ ࣟࢱ࢘࢖ࣝࢫ࣡ࢡࢳࣥ࡟ࡼࡿୗ⑩⑕ࡶࡳࡽࢀࡿࠋ

– ⣽⳦㸪┿⳦ឤᰁ⑕: ཯᚟, ᣢ⥆, 㔜⑕໬࡞࡝㸸BCG ࡟ࡼࡿ᧛✀ᛶឤᰁࡶ

⏕ࡌ࠺ࡿࠋ

– ᪥࿴ぢឤᰁ⑕㸸 ࢽ࣮ࣗࣔࢩࢫࢸ࢕ࢫ⫵⅖࡞࡝

ཧ⪃ᡤぢ㸸

– ៏ᛶⓗ࡞ୗ⑩ࡸయ㔜ቑຍ୙Ⰻ – ㌟యᡤぢ㸸ࣜࣥࣃ⤌⧊ࡢపᙧᡂ

– ⫘㦵㸪⫪⏥㦵㸪᳝య㸪⭠㦵⛸࡞࡝ࡢ㦵ࡢ␗ᖖ – Ⓨ㐩ࡢ㐜ࢀࡸ㞴⫈㸪ࡅ࠸ࢀࢇ࡞࡝ࡢ⚄⤒⑕≧

– ≉࡟㐜Ⓨ౛࡛⁐⾑ᛶ㈋⾑, ⾑ᑠᯈῶᑡ⑕, ⮬ᕫච␿ᛶ ⏥≧⭢⅖, ዲ㓟

⌫ቑከࡸ㧗IgE⾑⑕㸪⢾ᒀ⑓࡞࡝ࡢྜే

• ᳨ᰝᡤぢ

– ඾ᆺ౛࡛ࡣᮎᲈ⾑ࣜࣥࣃ⌫ࡢⴭῶ㸦<500/ȣl㸧ࠊᮎᲈ⾑ CD3+T ⣽⬊

<300/mm³, CD19+B⣽⬊, CD16+NK⣽⬊ࡀḞᦆ,ࡶࡋࡃࡣⴭῶࠋ

– ṧᏑ㓝⣲άᛶࡢ࠶ࡿሙྜࡶྵࡵࠊCD3+⣽⬊ࡀ⏕ᚋ2࠿᭶ᮍ‶<2000/mm³, 2࠿᭶ࠥ6࠿᭶ᮍ‶<3000/mm³, 6࠿᭶ࠥ1ṓᮍ‶<2500/mm³, 1ṓࠥ2ṓᮍ

‶<2000/mm³, 2ṓࠥ4ṓᮍ‶<800/mm³, 4ṓ௨ୖ<600/mm³ࢆ㝧ᛶᡤぢ࡜

ࡍࡿࠋ

– TRECsࡢప್ (<100 copies/ȣg DNA඲⾑)

ࡗ࡚ಖࡓࢀࡿ㸧

– ⬚㒊CT࡛㛫㉁ᛶ⫵⅖ࡸ⫵⬊⺮ⓑ⑕࡞࡝ࡢᡤぢ – ⬚⭢ࡸ2ḟࣜࣥࣃ⤌⧊ࡢḞᦆ

– 㚷 ู デ ᩿ 㸸SCID, ≉ ࡟ T-B-NK-SCID ࢆ ࿊ ࡍ ࡿ ࡶ ࡢ: RAG1, RAG2, DCLRE1C,PRKDC,NHEJ1,AK2࡞࡝ࡢ㑇ఏᏊ␗ᖖ࡟㉳ᅉࡍࡿSCIDࠋ – ὀពⅬ㸸㐍⾜ᛶࡢࣜࣥࣃ⌫ῶᑡࢆࡁࡓࡍࡓࡵ, ฟ⏕᫬᳨ᰝ࡛␗ᖖࡀࡳࡽ

ࢀ࡞ࡃ࡚ࡶྰᐃ࡛ࡁ࡞࠸ࠋ⏕ᚋ᪩ᮇࡢTRECsࡶప್࡟࡞ࡽ࡞࠸ࡇ࡜ࡶ࠶

ࡿࠋ d) デ᩿ᇶ‽

• 㑇ఏᏊゎᯒ ࡜ ADA㓝⣲άᛶ ࡢ⤖ᯝ࠿ࡽデ᩿ࢆ⾜࠺ࠋ

– ∦ഃ࢔ࣜࣝࡢdeletionࡸࢫࣉࣛ࢖ࢫ␗ᖖ࡞࡝ࡢ, DNAࣞ࣋ࣝࡢ㑇ఏᏊゎ ᯒ࡛ࡣ≉ᐃ࡛ࡁ࡞࠸ኚ␗ࡀᏑᅾࡋ, ࡑࡢሙྜࡣ array CGH࡞࡝࡟ࡼࡿࢥ

ࣆ࣮ᩘࡢホ౯ࡸcDNAࣞ࣋ࣝࡢゎᯒࡀᚲせ࡛࠶ࡿࠋ ࡋࡓࡀࡗ࡚, ㎿㏿デ

᩿ࡢࡓࡵ࡟ࡣADA㓝⣲άᛶ ᐃࡶ୪⾜ࡋ࡚⾜࡞࠺ࡇ࡜ࡀ㔜せ࡛࠶ࡿࠋ – ㉥⾑⌫ࡢࡳ࡛ADA㓝⣲άᛶࡀపୗࡍࡿ೺ᖖே (partial deficiency) ࡶᏑᅾ

ࡍࡿࡓࡵ, ℐ⣬⾑, ⓑ⾑⌫, ⓑ⾑⌫ศ⏬㸦༢᰾⌫ࡸዲ୰⌫㸧ࡸ⥺⥔ⱆ⣽⬊

࡞࡝࡛άᛶࢆ ᐃࡍࡿࠋ

– ADA㓝⣲άᛶࡀṇᖖࡢ1%௨ୗࡢ᫬, 㔜⑕ᆺADAḞᦆ⑕࡜デ᩿ࡍࡿࠋ㐜

Ⓨᆺࡢሙྜࡣ㸪㓝⣲άᛶࡢపୗ࡟ຍ࠼࡚, ⮫ᗋ⑕≧, ᳨ᰝᡤぢ, 㑇ఏᏊゎ ᯒ⤖ᯝࢆ⥲ྜࡋ࡚デ᩿ࡍࡿࠋ

– ㍺⾑ᚋࡣ㍺⾑⾑ᾮࡢ ADA άᛶ࡟ࡼࡾデ᩿ࡀᅔ㞴࡟࡞ࡿࡢ࡛ࠊ㍺⾑๓ࡢ ℐ⣬⾑࡞࡝ࢆಖᏑࡋ࡚࠾ࡃࡇ࡜ࡀᮃࡲࡋ࠸ࠋ

– ඲⾑ࡸ㉥⾑⌫୰ࡢdAXP ᐃࡶ⾜࡞࠺㸦἞⒪ຠᯝࡢホ౯࡟ࡶ㔜せ㸧ࠋ e) ୺࡞ྜే⑕

• ୰ᯡ⚄⤒⣔㸸ADHD, ᨷᧁⓗ⾜ື, ♫఍ᛶ⾜ືࡢ␗ᖖࠋdATP ࡜ total IQ ࡢ㛫࡟

㈇ࡢ┦㛵ࡀ࠶ࡿ࡜࠸ࢃࢀ࡚࠸ࡿࠋ

• ឤ㡢ᛶ㞴⫈㸸dATP ࡜ࡢ┦㛵ࡣ࡞࠸࡜࠸ࢃࢀ࡚࠸ࡿࠋ

• ࣜࣥࣃቑṪ⑌ᝈ(ERT୰ࡢ8౛)

• ⫵㸸㠀ឤᰁᛶࡢ⫵⅖, ⥺⥔໬, ⫵⬊⺮ⓑ⑕(43.8%)㸸௦ㅰ␗ᖖ࡟ࡼࡿྍ⬟ᛶ

• ⫢⮚㸸⫢ᶵ⬟㞀ᐖ

• 㦵᱁⣔:⫘㦵➃ࡢᣑᙇ㸪⫪⏥㦵ࡢኚᙧ㸪᳝య㸪⭠㦵⛸࡞࡝ࡢ㦵ࡢ␗ᖖ

• ⁐⾑ᛶᒀẘ⑕⑕ೃ⩌(HUS): 4౛ࡢሗ࿌(Gaspar, 2015)

• ⓶⭵⭘⒆㸸dermatofibrosarcoma protuberans (㝯㉳ᛶ⓶⭵⥺⥔⫗⭘) 8 ౛ࡢሗ࿌

(Fabio, 2012) f) 㔜⑕ᗘศ㢮

• ච␿୙඲ࡢ㔜⑕ᗘࡣṧᏑࡍࡿADA㓝⣲άᛶࡢ⛬ᗘ࡟┦㛵ࡍࡿࡀ, 㔜⑕ᗘࡣ௨ୗ

ࡢࡼ࠺࡟୺࡟⮫ᗋ⤒㐣࡟ᛂࡌ࡚ศ㢮ࡉࢀࡿ (Table 1)ࠋ

• ADA㑇ఏᏊኚ␗యࡑࢀࡒࢀࡢ㓝⣲άᛶࡶཧ⪃࡟ࡍࡿ(Table 2)ࠋ g) ⟶⌮᪉ἲ, ἞⒪

• ึᮇ἞⒪㸸

– ↓⳦⟶⌮, ẕங⚗Ṇ, ᢠ⏕๣(Pneumocystis ⫵⅖἞⒪ࡲࡓࡣண㜵ࡢࡓࡵࡢ ST ྜ๣ࡶྵࡴ㸧, ᢠ┿⳦๣, ࣐࢞ࣥࢢࣟࣈࣜࣥ⿵඘⒪ἲ, ࢩࢼࢪࢫ᭶ 1 ᅇࡢ➽ὀ

– ADA㓝⣲⿵඘⒪ἲ (ERT)㸸

࢘ࢩ⏤᮶ࡢ ADA 㓝⣲ࢆ࣏࢚ࣜࢳࣞࣥࢢࣜࢥ࣮ࣝฎ⌮ࡋࡓ〇๣

㸦PEG-ADA㸧ࢆ1-2ᅇ/㐌࡛➽ὀࡍࡿࠋ

PEG-ࣜࢥࣥࣅࢼࣥࢺADAࡀ㛤Ⓨࡉࢀ, ⌧ᅾ⮫ᗋ἞㦂୰࡛࠶ࡿࠋ άືᛶࡢឤᰁࡀ࠶ࡿሙྜ࡟ࡣ, ᩆ࿨ⓗ࡟㓝⣲⿵඘ࢆᐇ᪋ࡋ, ࡑࡢᚋ

࡟㐀⾑ᖿ⣽⬊⛣᳜࡬⛣⾜ࡍࡿࡇ࡜ࡀᮃࡲࡋ࠸ࠋ

• ᰿἞἞⒪㸸㐀⾑ᖿ⣽⬊⛣᳜ (HSCT), 㑇ఏᏊ἞⒪ (GT)

– ᭱㏆ࠊᙉᗘࢆ㍍ῶࡋࡓ๓ฎ⨨࡛ࡢࣞࣥࢳ࢘࢖ࣝࢫࢆ⏝࠸ࡓ㑇ఏᏊ἞⒪

(Farinelli et al 2014)ࡀⰋዲ࡞ᡂ⦼ࢆ࠶ࡆ࡚࠸ࡿࠋ h) ࣇ࢛࣮ࣟ࢔ࢵࣉᣦ㔪

• ࣜࣥࣃ⌫ᩘ, ࣜࣥࣃ⌫ศ⏬, ⾑ΎIgG, IgA, IgM, IgE, ⫢ᶵ⬟࡞࡝

• Total adenosine (AXP) & deoxyadenosine (dAXP): ඲⾑㸦㉥⾑⌫㸧

• ⾑₢ࡸ⾑Ύ୰ࡢADAάᛶ:≉࡟ERT୰

• TRECs

• HSCT ౛࡛ࡣྛ⾑⌫⣔࡛ࡢ࣓࢟ࣛゎᯒ, ๓ฎ⨨࡟ࡼࡿ▷ᮇⓗ, 㛗ᮇⓗ࡞๪స

⏝ホ౯ࡶ⾜࠺ࠋ

• GT౛࡛ࡣࡉࡽ࡟integration siteࡢホ౯ࡸᑟධຠ⋡, ࡑࢀࡒࢀࡢ⾑⌫⣔ࡢADA㓝

⣲άᛶࡢᐃᮇⓗ࡞ホ౯ࡶ⾜࡞࠺ࠋ

• ⬚㒊CT࡞࡝࡛ࡢ⫵⑓ኚࡢホ౯

• ⭡㒊㉸㡢Ἴ᳨ᰝ࡞࡝࡟ࡼࡿ⫢, ⭠⟶࡞࡝ࡢホ౯

• ERT୰ࡢ⫢ⱆ⭘(1౛), ⫢⒴(1౛㸧ࡢሗ࿌

• య㔜ቑຍ, ୗ⑩, ᰤ㣴≧ែࡢホ౯

• 㠀㐀⾑⣔㸸 ⢭⚄Ⓨ㐩, 㞴⫈ࡢ᭷↓ࡢホ౯࡞࡝

i) ணᚋࠊᡂேᮇࡢㄢ㢟

• 㐀⾑⣔ࡢᵓ⠏ࡀᡂຌࡋ࡚ࡶ, ⚄⤒Ꮫⓗ␗ᖖ, 㞴⫈࡞࡝ࢆ⏕ࡌ, QOLపୗࢆᣍࡃࡇ

࡜ࡀከ࠸ࠋ

• ᡂே࡛デ᩿ࡉࢀࡿ late onset ࡢ౛࡛ࡣ, ච␿␗ᖖ࡜᫆ឤᰁᛶࡣ㍍ᗘ࡛࠶ࡿࡀ, デ

᩿ࡀ㐜ࢀࡿ࡜៏ᛶ⫵⑌ᝈ࡞࡝ࡀ㐍⾜ࡋ࡚࠸ࡿࡇ࡜ࡀከࡃ, ᪩ᮇࡢデ᩿ࡀᮃࡲࡋ

࠸ࠋࡇࡢሙྜࡢ἞⒪᪉㔪࡟ࡘ࠸࡚ࡣಶࠎุ࡛᩿ࡏࡊࡿࢆᚓ࡞࠸ࡀ, ⫵⑓ኚࡸ⫢㞀 ᐖ࡞࡝ࡣ௦ㅰ␗ᖖ࡛⏕ࡌࡿྍ⬟ᛶࡀ࠶ࡿࡓࡵ, ERTࡣ⪃៖ࡍ࡭ࡁ࡜ᛮࢃࢀࡿࠋ j) デ⒪ୖὀពࡍ࡭ࡁⅬ

• ௦ㅰ⏘≀ࡢ⵳✚࡟క࠸㐍⾜ᛶࡢSCIDࢆ࿊ࡍࡿࡓࡵ, ฟ⏕┤ᚋ࡟ࡣ␗ᖖࡀࡳࡽࢀ

࡞࠸ሙྜࡀከ࠸ࠋࡑࡢࡓࡵ, ␲ࢃࡋ࠸ሙྜ࡟ࡣ, ච␿⣔ࡢ␗ᖖࡀࡳࡽࢀ࡞ࡃ࡚ࡶ

㑇ఏᏊゎᯒ and/or 㓝⣲άᛶ ᐃࢆ⾜࠸,ฟ⏕ᚋࡢࣇ࢛࣮ࣟࢆ⥅⥆ࡍࡿࡇ࡜ࡀ㔜 せ࡛࠶ࡿࠋ

• ඲㌟≧ែࡀ୙Ⰻࡔࡗࡓࡾ, ឤᰁࢆⓎ⑕ࡋ࡚࠸ࡿሙྜ࡟ࡣ, PEG-ADA ᢞ୚࡟ࡼࡾ

඲㌟≧ែࢆᨵၿࡉࡉࡏ࡚࠿ࡽ㐀⾑ᖿ⣽⬊⛣᳜࡟⛣⾜ࡍࡿࡇ࡜ࡀᮃࡲࡋ࠸ࠋ

• HSCT ࡞࡝࡟ࡼࡾ㐀⾑⣔ࡢᵓ⠏ࡀᡂຌࡋ࡚ࡶ, 㠀㐀⾑⣔ࡢ㞀ᐖࡣ⏕ࡌࡿࡇ࡜ࡀ ከࡃ, Ⓨ⑕ண㜵ࡣ௒ᚋࡢㄢ㢟࡛࠶ࡿࠋ

㼀㼍㼎㼘㼑㻌㻝㻌㻌㔜⑕ᗘศ㢮 ‡ ච␿୙඲䛾㔜⑕ᗘ䛿ṧᏑ䛩䜛㻭㻰㻭㓝⣲άᛶ䛾⛬ᗘ䛻 ┦㛵䛩䜛䛜㻘㻌 㔜⑕ᗘ䛿௨ୗ䛾䜘䛖䛻୺䛻⮫ᗋ⤒㐣䛻 ᛂ䛨䛶ศ㢮䛥䜜䜛䚹 Ḟ ᦆ ⑕ 㔜 ⑕ ᗘ ศ 㢮 㔜⑕ᆺ ⏕ୗ᫬䛛䜙㧗ᗘ䛾䝸䞁䝟⌫ῶᑡ䜢 䛝䛯䛧䚸 ϭ ṓ ௨ୗ䛷デ᩿䛥䜜䜛䠊 ᭱䜒ከ䛔䠊 㐜Ⓨᆺ ϭ ࠥ ϭϬ ṓ䛷ᛴ㏿䛻ᝏ໬䜢ㄆ䜑デ᩿ 䛥䜜䜛䠊 ϭϬ ࠥ ϭϱй 䜢༨䜑䜛䠊 ᬌⓎᆺ ⦆ᚎ䛻㐍⾜䛧 ϭϬ ṓ௨㝆䛻デ᩿ 䛥䜜䜛䠊⛥ 䛺 ⑓ ᆺ䠊 㒊ศ Ḟᦆᆺ ㉥⾑⌫䛷䛿㓝⣲άᛶ䛜పୗ䛩䜛䛜䠈௚ 䛾⣽⬊ 䛷䛿 పୗ䛫 䛪 ච␿⬟䜒ṇᖖ䠊

㼀㼍㼎㼘㼑㻌 㻞㻌 㻌 㻭㻰㻭 㑇ఏᏊኚ␗య䛾㓝⣲άᛶ ƌƌ ĞĚŽŶĚŽͲs Ğ ŐĂ & y Ğƚ Ăů͘ŵ:,Ƶŵ 'ĞŶĞƚ͘ϭϵϵϴ͘

デ⒪࢞࢖ࢻࣛ࢖ࣥ

࢘࢖ࢫࢥࢵࢺ Ã ࢜ࣝࢻࣜࢵࢳ㸦 Wiskott-Aldrich 㸧⑕ೃ⩌

D ⑌ᝈᴫせ

࢘࢖ࢫࢥࢵࢺѿ࢜ࣝࢻࣜࢵࢳ⑕ೃ⩌:LVNRWW$OGULFKV\QGURPH௨ୗ:$6࡜␎ࡣࠊ

᫆ឤᰁᛶࠊ⾑ᑠᯈῶᑡࠊ‵⑈ࢆ୺ᚩ࡜ࡍࡿ;㐃㙐ᛶච␿୙඲⑕࡛࠶ࡾࠊཎᅉ㑇ఏᏊ ࡣ:$6࡛࠶ࡿࠋ⾑ᑠᯈῶᑡࡢࡳࢆ࿊ࡍࡿ⑓ᆺ࡜ࡋ࡚;㐃㙐ᛶ⾑ᑠᯈῶᑡ⑕;OLQNHG WKURPERF\WRSHQLD௨ୗ;/7࡜␎ࡀ࠶ࡿࠋ

E ␿Ꮫ

ᮏ㑥࡛ࡣࡇࢀࡲ࡛౛௨ୖࡢ⑕౛Ⓩ㘓ࡀ࡞ࡉࢀ࡚࠸ࡿࠋ;/7ࡢ⑕౛ࡣ៏ᛶ,73࡜ࡋ

࡚ᮍデ᩿౛ࡀከ࠸࡜᥎ ࡉࢀࡿࡓࡵࠊ:$6␗ᖖ⑕࡜ࡋ࡚ࡣ᭦࡟ከᩘ౛Ꮡᅾࡍࡿ࡜᥎  ࡉࢀࡿࠋ

F デ᩿ᇶ‽ࠊデ᩿ࡢᡭᘬࡁ ⑓ᅉ࣭Ⓨ⑕ᶵᗎ࡜ศᏊ⑓ែ

:$6ࡣࠊᖺ࡟:LVNRWWࡀࠊᖺ࡟$OGULFKࡀሗ࿌ࡋࡓච␿୙඲ࢆక࠺≉ᚩⓗ

࡞⑕ೃ⩌࡛࠶ࡾࠊࢧ࢖ࢬࡢῶᑡࢆక࠺⾑ᑠᯈῶᑡࠊ‵⑈ࠊ᫆ឤᰁᛶࢆ୺ᚩ࡜ࡋࠊ㏻

ᖖ⏨ඣ࡟Ⓨ⑕ࡍࡿ;ᰁⰍయ㐃㙐ᛶཎⓎᛶච␿୙඲⑕࡛࠶ࡿࠋᖺ࡟;ᰁⰍయୖ

;S࡟Ꮡᅾࡍࡿ:$6㑇ఏᏊኚ␗ࡀ:$6ࡢᇶᮏ⑓ᅉ࡛࠶ࡿ࡛࠶ࡿࡇ࡜ࡀሗ࿌ࡉࢀࡓ

ࠋ:$6㑇ఏᏊࡣ࢚ࢡࢯࣥࡼࡾ࡞ࡾࠊಶࡢ࢔࣑ࣀ㓟ࡼࡿ࡞ࡿ:$63⺮ⓑ㉁ࢆࢥ࣮

ࢻࡋ࡚࠸ࡿࠋ⌧ᅾࡲ࡛ከࡃࡢ㑇ఏᏊ␗ᖖࡀሗ࿌ࡉࢀ࡚࠾ࡾࠊኚ␗ࡣ:$6㑇ఏᏊࡢ࡝ࡇ

࡟ࡶ⏕ࡌᚓࡿࡀࠊ1ᮎ➃ࡢ࢚ࢡࢯࣥ࡟㞟୰ࡋ࡚࠸ࡿⅬࡀ≉ᚩ࡛࠶ࡾࠊࡑࡢከࡃࡀ

࣑ࢫࢭࣥࢫኚ␗࡛࠶ࡿࠋ㑇ఏᏊᆺ⾲⌧ᆺ㸦㔜⑕ᗘ㸧ࡢ㛵㐃ᛶ࡜ࡋ࡚ࠊࣜࣥࣃ⌫࡟࠾ࡅ

ࡿ:$63⺮ⓑ㉁ࡢⓎ⌧ࡢ᭷↓ࡀ┦㛵ࡋࠊ㔜⑕౛ࡣ:$63⺮ⓑࡀⓎ⌧ࡋ࡚࠾ࡽࡎࠊࢼࣥࢭ

ࣥࢫኚ␗㸪ࣇ࣮࣒ࣞࢩࣇࢺࢆక࠺ᤄධࠊḞኻࡀከ࠸ࠋࡈࡃ⛥࡟ࠊ:$6ࡣዪඣ࡟ࡶⓎ

⑕ࡋࡓ࡜ࡢሗ࿌ࡀ࠶ࡿࠋ

ྠᵝࡢ㑇ఏᙧᘧ࡛ච␿୙඲ࢆకࢃࡎ⾑ᑠᯈῶᑡࡢࡳࢆ࿊ࡍࡿ;/7ࡀ࠶ࡾࠊ἞⒪᢬ᢠ ᛶࡢච␿ᛶ⾑ᑠᯈῶᑡᛶ⣸ᩬ⑓㸦,73㸧ࡸ௚ࡢ㑇ఏᏊ⾑ᑠᯈῶᑡ⑕࡜ࡢ㚷ูࡀ㔜せ࡜࡞

ࡿࠋ;/7ࢆྵࡴ㍍⑕౛ࡣ:$63⺮ⓑࡀⓎ⌧ࡋ࡚࠸ࡿ౛ࡀከࡃࠊ࣑ࢫࢭࣥࢫኚ␗౛ࡀከ࠸

ࠋ⾑ᑠᯈ࡛ࡢ:$63⺮ⓑࡢⓎ⌧ࡣ඲౛᳨ฟឤᗘ௨ୗ࡛࠶ࡾࠊ:$63␗ᖖ⑕ࡢ࡯ࡰ඲౛ࡀ

⾑ᑠᯈῶᑡࢆక࠺ࡇ࡜࡜㛵㐃ࡍࡿࠋ

㏆ᖺࠊᖖᰁⰍయຎᛶ㑇ఏᙧᘧࡢ:$6࡜ࡋ࡚:$63,QWHUDFWLQJSURWHLQ:,3ࢆࢥ࣮

ࢻࡍࡿ:,3)ࢆཎᅉ㑇ఏᏊ࡜ࡍࡿ⑓ᆺࡀሗ࿌ࡉࢀ࡚࠸ࡿࠋ

⮫ᗋ⑕≧ࠊ㌟యᡤぢ

᫆ឤᰁᛶ

᫆ឤᰁᛶࡢ⛬ᗘࡣ⑕౛࡟ࡼࡾ␗࡞ࡿࡢࡀ≉ᚩ࡛࠶ࡿࠋྂ඾ⓗ:$6ࡣஙᗂඣᮇ࠿ࡽ

୰⪥⅖ࠊ⫵⅖ࠊ๪㰯⭍⅖ࠊ⓶⭵ឤᰁ⑕ࠊ㧊⭷⅖࡞࡝ࢆ཯᚟ࡍࡿࠋ㉳⅖⳦࡜ࡋ࡚ࡣ⫵⅖

⌫⳦ࡸࣈࢻ࢘⌫⳦ࡀከࡃࠊ┿⳦ឤᰁ࡛ࡣ࢝ࣥࢪࢲࠊ࢔ࢫ࣌ࣝࢠࣝࢫࡀࠊཎ⹸࡛ࡣ࢝ࣜ

ࢽ⫵⅖ࡀᑡᩘ࡛ぢࡽࢀࡿࠋ࢘࢖ࣝࢫឤᰁ࡛ࡣࠊ࣊ࣝ࣌ࢫᒓ࢘࢖ࣝࢫឤᰁ⑕㸦+69㺂9=9㺂

&09㺂(%9㸧ࡀከ࠸ࡢࡀ≉ᚩ࡛࠶ࡿࠋ

⾑ᑠᯈῶᑡ

࡯ࡰ඲౛࡛ぢࡽࢀࠊฟ⏕┤ᚋ࠿ࡽぢࡽࢀࡿࡇ࡜ࡀከࡃࠊึⓎ⑕≧࡜ࡋ࡚ࡣ⾑౽ࠊ

⓶ୗฟ⾑ࠊ⣸ᩬࡀከ࠸ࠋ㢌⵹ෆฟ⾑ࡣ,73ࡼࡾ᫂ࡽ࠿࡟㧗㢖ᗘ࡛࠶ࡿࠋ⾑ᑠᯈࢧ࢖ࢬ ࡢῶᑡ㸦ᑠᆺ⾑ᑠᯈ㸧ࢆక࠸ࠊ┠ど࡛☜ㄆࡍࡿࡀࠊᖹᆒ⾑ᑠᯈᐜ✚0HDQ3ODWHOHW 9ROXPH039ࡣపୗࡋ࡚࠸ࡿ౛ࡀከ࠸ࠋ⾑౽ࡣ⾑ᑠᯈῶᑡࡢ௚࡟ࠊ᪩ᮇⓎ⑕⅖⑕ᛶ⭠

⑌ᝈࡢྜేࡀཎᅉ࡜⪃࠼ࡽࢀ࡚࠸ࡿࠋ

‵⑈

‵⑈ࡣ࢔ࢺࣆ࣮ᛶ‵⑈ᵝ࡛ࠊ㞴἞࡛࠶ࡿࠋ

᳨ᰝᡤぢ

⾑ᑠᯈῶᑡࢆㄆࡵࡿࠋᑠᆺ⾑ᑠᯈ࡛࠶ࡿሙྜࡀከ࠸ࠋ

7⣽⬊ᩘࡢῶᑡ࡜&'ᢠయ่⃭࡟ᑐࡍࡿ཯ᛂపୗࡀࡳࡽࢀࡿࠋ ච␿ࢢࣟࣈ್ࣜࣥࡣ,J0పୗࠊ,J$ୖ᪼ࠊ,J(ୖ᪼ࢆㄆࡵࡿࠋ

ከ⢾㢮ᢠయࠊྠ✀⾑⌫จ㞟⣲౯࡞࡝ࡢ≉␗ⓗᢠయ⏘⏕⬟ࡣపୗࡍࡿࠋ 1.άᛶࡣ༙ᩘ࡛పୗࡍࡿࠋ

⿵య౯ࡣṇᖖ࡜ࡉࢀࡿࡀࠊዲ୰⌫࠾ࡼࡧ༢⌫ࡢ㐟㉮⬟ࡣపୗࡍࡿ౛ࡀከ࠸ࠋ :$6:,3)㑇ఏᏊኚ␗

㚷ูデ᩿㸦ࣇ࣮ࣟࢳ࣮ࣕࢺཧ↷㸧

ୖグ⑕≧ཬࡧ᳨ᰝᡤぢࢆ඲࡚ㄆࡵࡿ⑕౛ࡣᑡ࡞࠸ࡓࡵࠊ⾑ᑠᯈῶᑡ⑕ཬࡧࡑࡢ௚ࡢ

ୖグ⑕≧ࠊᐙ᪘Ṕࡢ᭷↓࠿ࡽᮏ⑌ᝈࡀ␲ࢃࢀࡿሙྜࡣࠊ⾑ᾮච␿Ꮫⓗ᳨ᰝཬࡧᚋኳⓗ

せᅉࡢ㝖እࢆ⾜ࡗࡓᚋࠊ:$6㑇ఏᏊኚ␗ࢆ☜ㄆࡍࡿࠋࣇ࣮ࣟࢧ࢖ࢺ࣓ࢺ࣮ࣜἲ࡟ࡼࡿ

:$63⺮ⓑⓎ⌧పୗࡢ᳨ウࡣ㎿㏿ࢫࢡ࣮ࣜࢽࣥࢢἲ࡜ࡋ࡚᭷⏝࡛࠶ࡿࠋ

:$63⺮ⓑ㉁Ⓨ⌧పୗࡀ࠶ࡿࡶࡢࡢ:$6㑇ఏᏊኚ␗ࢆㄆࡵ࡞࠸ሙྜࡣ:,3)㑇ఏᏊ᳨

⣴ࢆ᳨ウࡍࡿࠋ

デ᩿ᇶ‽

⮫ᗋ⑕≧࡜᳨ᰝᡤぢࢆ‶ࡓࡋࠊ:$6㑇ఏᏊኚ␗ࡀ࠶ࡿሙྜ࡟:$6࠶ࡿ࠸ࡣ;/7࡜☜ᐃ デ᩿ࡍࡿࠋࣇ࣮ࣟࢧ࢖ࢺ࣓ࢺ࣮ࣜἲࡣ㎿㏿デ᩿࠾ࡼࡧ:$63⺮ⓑⓎ⌧పୗࡢ☜ㄆ࡟ࡼࡿ

ணᚋࡢ᥎ᐃ࡟᭷⏝࡛࠶ࡿࠋ

Gྜే⑕

⮬ᕫච␿⑌ᝈ

,J$⭈⑕ࠊ⮬ᕫච␿ᛶ⁐⾑ᛶ㈋⾑ࠊච␿ᛶ⾑ᑠᯈῶᑡᛶ⣸ᩬ⑓,73ࠊ㛵⠇⅖ࠊ⾑⟶

⅖ࠊ⅖⑕ᛶ⭠⑌ᝈ࡞࡝ࡢ⮬ᕫච␿ᛶ⑌ᝈࢆྜేࡍࡿࡇ࡜ࡀ࠶ࡿࠋ

ᝏᛶ⭘⒆

ᝏᛶࣜࣥࣃ⭘ࡀከࡃࠊ(%9 㛵㐃ࢆྵࡴ % ⣽⬊ᛶ⭘⒆ࡀከ࠸ࡢࡀ≉ᚩⓗ࡛࠶ࡿࠋ⛥

࡟⬻⭘⒆ࡢሗ࿌ࡶ࠶ࡿࠋ:$63⺮ⓑ㝜ᛶ౛࡟ከ࠸ࠋ

H 㔜⑕ᗘศ㢮㸸㔜㔜⑕

ᚑ᮶ࡼࡾ:$6;/7࡟࠾࠸࡚ࡣࠊୗグࡢ㔜⑕ᗘศ㢮ࡀᥦၐࡉࢀ࡚࠸ࡿࠋ

ࢡࣛࢫ;/7⾑ᑠᯈῶᑡࡢࡳ

ࢡࣛࢫ;/7⾑ᑠᯈῶᑡ㸩㍍⑕୍㐣ᛶࡢ‵⑈s㍍⑕ឤᰁ⑕

ࢡࣛࢫ:$6⾑ᑠᯈῶᑡ㸩ᣢ⥆ᛶࡢ‵⑈DQGRU཯᚟ᛶឤᰁ⑕

ࢡࣛࢫ:$6⾑ᑠᯈῶᑡ㸩ᣢ⥆ᛶࡢ‵⑈཯᚟ᛶ㔜⑕ឤᰁ⑕

ࢡࣛࢫ:$6⾑ᑠᯈῶᑡ㸩ᣢ⥆ᛶࡢ‵⑈DQGRU཯᚟ᛶឤᰁ⑕

⮬ᕫච␿⑌ᝈ࠶ࡿ࠸ࡣᝏᛶ⭘⒆ࡢྜే

I ⟶⌮᪉ἲ㸦ࣇ࢛࣮ࣟ࢔ࢵࣉᣦ㔪㸧ࠊ἞⒪

᰿἞⒪ἲ

᰿἞ⓗ἞⒪࡜ࡋ࡚ࡣྠ✀㐀⾑ᖿ⣽⬊⛣᳜ࡀ⾜ࢃࢀࡿࠋ:$63⺮ⓑⓎ⌧ࢆㄆࡵࡎࠊឤᰁ

ࢆ⧞ࡾ㏉ࡍ⑕౛࡛ࡣ᪩ᮇ࡟⛣᳜ࢆ⪃៖ࡍ࡭ࡁ࡛࠶ࡿࠋ⾑ᑠᯈῶᑡࡀ୺యࡢ ;/7 ⑕౛࡛

ࡶࠊ㔜⠜࡞ฟ⾑ࠊ⮬ᕫච␿⑌ᝈࠊᝏᛶ⭘⒆ࠊ⭈⅖ࢆྜేࡍࡿࡇ࡜ࡀ࠶ࡾࠊ⛣᳜㐺ᛂ࡜࡞

ࡾ࠺ࡿ࡜⪃࠼ࡽࢀࡿࡀࠊ⛣᳜᫬ᮇࡸ⮳㐺๓ฎ⨨࡟ࡘ࠸࡚ࡣ௒ᚋࡢ⑕౛⵳✚ࡀ㔜せ࡛࠶ࡿࠋ ṓ௨ୗࡢ⑕౛ࡣ⣙ ࡢ⛣᳜ᚋ㛗ᮇ⏕Ꮡ⋡࡛࠶ࡿࡀࠊ ṓ௨ୖ࡛ࡣᵝࠎ࡞ྜే⑕࡟ࡼ

ࡾᡂຌ⋡ࡀపࡃ࡞ࡿⅬ࡟␃ពࡍ࡭ࡁ࡛࠶ࡿࠋ⛣᳜๓ฎ⨨ἲࡣ㦵㧊◚ቯⓗ๓ฎ⨨࡟ࡼࡿ

ྠ✀㦵㧊⛣᳜ࡀ୺య࡜࡞ࡗ࡚࠸ࡿࡀࠊ᭱㏆ࡣ⮖ᖏ⾑⛣᳜ࡸ㦵㧊㠀◚ቯⓗ๓ฎ⨨࡟ࡼࡿ⛣

᳜ࡢᡂຌ౛ࡶሗ࿌ࡉࢀ࡚࠸ࡿࠋ

㏆ᖺࠊ㑇ఏᏊ἞⒪ࡢሗ࿌ࡀ࡞ࡉࢀ࡚࠸ࡿࠋ:$63 ࣀࢵࢡ࢔࢘ࢺ࣐࢘ࢫ㐀⾑ᖿ⣽⬊࡟ࣞ

ࢺࣟ࢘࢖ࣝࢫ࣋ࢡࢱ࣮࡟࡚ṇᖖ:$63ࢆᑟධࡋࠊ࣐࢘ࢫ⾲⌧ᙧࡢᨵၿࢆᚓࡓሗ࿌ࡀ࠶ࡿ

ࠋࡲࡓࠊ᭱㏆ :$6 ⑕౛࡟ᑐࡍࡿ㐀⾑ᖿ⣽⬊࡬ࡢ㑇ఏᏊ἞⒪ࡢሗ࿌ࡀ࡞ࡉࢀ࡚࠾ࡾ ࠊ ᨵⰋࡉࢀࡓ㑇ఏᏊᑟධ࣋ࢡࢱ࣮࡟ࡼࡿ᭷ຠᛶࡀ♧ࡉࢀ࡚࠸ࡿࠋ

ᨭᣢ⒪ἲ

㔜኱ฟ⾑ࡢ㢖ᗘࡣ,73࡜ẚ㍑ࡋ᭷ព࡟㧗࠸࡜⪃࠼ࡽࢀࡿࠋ⾑ᑠᯈῶᑡ࡟ᑐࡍࡿ᦬⭁࡟

ࡘ࠸࡚ࡣࠊከࡃࡢ⑕౛࡛⾑ᑠᯈቑຍࡀᚓࡽࢀࡿࡀࠊ⤒㐣࡜࡜ࡶ࡟ῶᑡࡍࡿࡇ࡜ࡶ࠶ࡿࠋ

ࡲࡓࠊឤᰁ⑕ࡢࣜࢫࢡࡀቑຍࡍࡿࡇ࡜࠿ࡽ㐺ᛂࡣៅ㔜࡟⪃៖ࡍࡿᚲせࡀ࠶ࡾࠊ᥎ዡࡣࡉ

ࢀ࡚࠸࡞࠸ࠋ࣐࢞ࣥࢢࣟࣈࣜࣥ኱㔞⒪ἲࡸࢫࢸࣟ࢖ࢻ๣ࡣ㏻ᖖຠᯝ࡟ஈࡋࡃࠊ,73ྜే

౛ࡸᢠ⾑ᑠᯈᢠయ㝧ᛶ౛࡛ࡣ5LWX[LPDEࡀ᳨ウࡉࢀࡿ⑕౛ࡶ࠶ࡿࠋ᭱㏆ࠊ୍㒊⑕౛࡟࠾

࠸࡚ࢺ࣏ࣟࣥ࣎࢖࢚ࢳࣥసື⸆ࡢ᭷ຠᛶࡀሗ࿌ࡉࢀ࡚࠸ࡿࠋ⾑ᑠᯈ㍺⾑ࡣࠊ㔜⑕ฟ⾑ࠊ ᡭ⾡᫬ࡣࡸࡴࢆᚓ࡞࠸ࠋ

‵⑈ࡣ἞⒪࡟㞴῰ࡍࡿࡀࠊ୍⯡ⓗ࡞࢔ࢺࣆ࣮ᛶ⓶⭵⅖἞⒪࡟‽ࡌࡓ἞⒪ࢆ⾜࠸ࠊ㣗≀

࢔ࣞࣝࢠ࣮ࡀ᫂ࡽ࠿࡛࠶ࢀࡤ㝖ཤ㣗ࢆ⪃៖ࡍࡿࠋ).㌾⭯ࡀᑐ⑕ⓗ࡟᭷ຠ࡛࠶ࡗࡓ⑕

౛ࡶሗ࿌ࡉࢀ࡚࠸ࡿࠋ

ឤᰁ⑕ᑐ⟇࡜ࡋ࡚ࡣ๓㏙ࡢዴࡃ⣽⳦ࠊ࣊ࣝ࣌ࢫᒓ࢘࢖ࣝࢫ⩌ࠊ┿⳦ឤᰁ⑕ࡀከ࠸ࡓࡵࠊ

⮫ᗋ⤒㐣࡟ᛂࡌ࡚ࠊྂ඾ⓗ:$6⑕౛࡟ᑐࡋ࡚ࡣ67ྜ๣ࠊᢠ⳦๣ࠊᢠ┿⳦๣ࠊᢠ࢘࢖ࣝ

ࢫ๣ࡢண㜵ⓗ࠶ࡿ࠸ࡣ἞⒪ⓗᢞ୚ࢆ⾜࠺ࠋȚࢢࣟࣈࣜࣥࡢᐃᮇⓗ⿵඘ࡣࠊ,J*PJGO ࡢ⑕౛ࡸ㔜⑕ឤᰁ᫬࡟ࡣ⪃៖ࡍࡿࠋ࣊ࣝ࣌ࢫᒓ࢘࢖ࣝࢫឤᰁ⑕ࡢࣜࢫࢡࡀ㧗࠸ࡓࡵࠊ(%9

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J

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ᮏ㑥࡟࠾ࡅࡿච␿୙඲ྜే౛ࡢᖹᆒ㛗ᮇ⏕Ꮡᖺ㱋ࡣ ṓ࡜ࡉࢀࡿࠋឤᰁ⑕ࠊฟ⾑ࠊ ᝏᛶ⭘⒆ࡀ୺࡞Ṛᅉ࡛࠶ࡾࠊ ṓࡲ࡛ࡢṚᅉࡢ࡯࡜ࢇ࡝ࡣឤᰁ⑕࡜ฟ⾑࡛࠶ࡿࠋ:$63

⺮ⓑ㉁Ⓨ⌧㝜ᛶ౛ࡣ㝧ᛶ౛࡜ẚ㍑ࡋࠊ㛗ᮇணᚋࡣ᭷ព࡟పୗࡍࡿࠋ

᫆ឤᰁᛶࢆకࢃ࡞࠸;/7࡛ࡢ⏕Ꮡ⋡ࡣྂ඾ⓗ:$6ࡼࡾࡶⰋዲ࡛࠶ࡿࡀࠊ⤒㐣࡜࡜ࡶ࡟

ฟ⾑ࠊ,J$⭈⑕࠿ࡽࡢ⭈୙඲ࠊ⮬ᕫච␿⑌ᝈࡸᝏᛶ⭘⒆ࡢྜే⋡ࡀቑຍࡋࠊ㛗ᮇⓗ࡞↓

⑓⏕Ꮡ⋡ࡣ⤒㐣࡜࡜ࡶ࡟పୗࡍࡿࠋ

ྠ✀㐀⾑ᖿ⣽⬊⛣᳜ࢆ᪋⾜ࡋࡓ⑕౛ࡣࠊᡂேᮇ࡟⮳ࡗ࡚ࡶ⛣᳜ᚋࡢᬌᮇ㞀ᐖ࡟ὀពࡋ

ᮇ௨㝆࡛ࡶฟ⾑ഴྥࠊ⮬ᕫච␿⑌ᝈࡸᝏᛶ⭘⒆ࡢྜే࡟ὀពࡋࡓ㛗ᮇⓗ࡞⟶⌮ࡀᚲせ࡛

࠶ࡿࠋ K

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ஙඣᮇ࠿ࡽࡢ⾑ᑠᯈῶᑡ࡟క࠺ฟ⾑ഴྥ࡜ࡋ࡚⓶ୗฟ⾑࣭⣸ᩬࡸ⾑౽ࢆక࠺ሙྜࠊ᫆

ឤᰁᛶࢆ␲࠺⤒㐣ࡀ࠶ࡿሙྜࠊ‵⑈ࢆక࠺ሙྜࡣࠊᑓ㛛་࡜┦ㄯࡋ࡚:$6ࡢ㚷ูデ᩿ࢆ

㐍ࡵࡿࡇ࡜ࡀ㔜せ࡛࠶ࡿࠋ

἞⒪᢬ᢠᛶ៏ᛶ,73ࡢ୰࡟;/7⑕౛ࡀᏑᅾࡍࡿྍ⬟ᛶࡀ࠶ࡿࡓࡵࠊ㑇ఏᛶ⾑ᑠᯈῶᑡ

⑕࡜ࡋ࡚;/7ࢆ㚷ูデ᩿࡟ධࢀࡿࡇ࡜ࡀᚲせ࡛࠶ࡿࠋ

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ẟ⣽⾑⟶ᣑᙇᛶ㐠ືኻㄪ⑕ࡲࡓࡣẟ⣽⾑⟶ᣑᙇᛶᑠ⬻ኻㄪ⑕

ẟ⣽⾑⟶ᣑᙇᛶ㐠ືኻㄪ⑕㸦A-T㸧࡟ࡼࡿච␿୙඲⑕ࡣࠊ≉ᚩⓗ࡞⑕ೃࢆక࠺ච␿୙඲⑕࡟ศ 㢮ࡉࢀࠊ㐠ືኻㄪࠊẟ⣽⾑⟶ᣑᙇࢆ୺⑕≧࡜ࡋࠊᵝࠎ࡞⛬ᗘ࡛ච␿୙඲⑕ࢆྜేࡍࡿࠋከࡃࡢ ᝈ⪅ࡣṓࡢᚋ༙ࡼࡾṌ⾜ᅔ㞴ࡀฟ⌧ࡋࠊṓྎ࡛㌴᳔Ꮚࡀᚲせ࡟࡞ࡿࠋ║⌫ࡲࡓࡣ㢦㠃ࡢẟ

⣽⾑⟶ᣑᙇࡣṓ࡛Ẽ࡙࠿ࢀࡿࡇ࡜ࡀከ࠸ࠋከࡃࡢᝈ⪅࡛ప࣐࢞ࣥࢢࣟࣈࣜࣥ⾑⑕ࡢࡓࡵ཯

᚟ᛶࡢ࿧྾ჾឤᰁ⑕ࢆྜేࡍࡿࠋච␿୙඲ࡣ」ྜᆺච␿୙඲࡛࠶ࡿࡀࠊప࣐࢞ࣥࢢࣟࣈࣜࣥ⾑

⑕ࡀᵝࠎ࡞⛬ᗘ࡟ㄆࡵࡽࢀࡿࠋஙᗂඣᮇ࡟⮴Ṛⓗ࡜࡞ࡿ᪥࿴ぢឤᰁ⑕ࡢྜేࡣ࡞࠸ࡀࠊୖୗẼ 㐨ࡢ᫆ឤᰁᛶࡣ㧗㢖ᗘ࡟ㄆࡵࡽࢀࠊᄟୗㄪ⠇㞀ᐖ࡟ࡼࡾࠊㄗᄟᛶ⫵⅖ࢆⓎ⑕ࡍࡿࡇ࡜ࡀከ࠸ࠋ 㐠ືኻㄪࡢ࠶ࡿඣ࡛ࠊୖୗẼ㐨ࡢ཯᚟ឤᰁࡸࠊẟ⣽⾑⟶ᣑᙇ⑕ࢆྜేࡋ࡚࠸ࢀࡤデ᩿ࢆ␲࠸ࠊ

⾑ᾮ᳨ᰝ࡛ǂ-ࣇ࢙ࢺࣉࣟࢸ࢖ࣥࡢୖ᪼ࡸࣜࣥࣃ⌫ࡢᰁⰍయ␗ᖖࢆ᳨ฟࡍࡿࡇ࡜࡛ࠊデ᩿࡛ࡁࡿࠋ

☜ᐃデ᩿ࡣATM 㑇ఏᏊゎᯒ࡟ࡼࡿࠋ20-30㸣ࡢ⑕౛࡟ᝏᛶ⭘⒆ࢆྜేࡋࠋࡲࡓࠊ㛫㉁ᛶ⫵⅖ࠊ Ẽ⟶ᨭᣑᙇ⑕ࡢྜేࡶከ࠸ࠋឤᰁண㜵ࡢࡓࡵ࡟ᢞ⸆ࡸච␿ࢢࣟࣈࣜࣥᢞ୚ࡀ⾜ࢃࢀࡿࡀࠊ᭷ຠ

ᛶࡣ᫂ࡽ࠿࡜ࡣ࡞ࡗ࡚࠸࡞࠸ࠋ᰿ᮏⓗ἞⒪ἲࡣ࡞࠸ࠋ

࠙デ᩿᪉ἲࠚ A. ⮫ᗋ⑕≧

1. Ṍ⾜㛤ጞ࡜ඹ࡟᫂ࡽ࠿࡟࡞ࡿṌ⾜ኻㄪ㸦యᖿኻㄪ㸧㸸ᚲⓎ⑕≧

ᚎࠎ࡟☜ᐇ࡟㐍⾜㸦2ṓ࠿ࡽ5ṓࡲ࡛ࡢ㛫࡟ࡣ㐍⾜ࡀ࣐ࢫࢡࡉࢀࡿࡇ࡜ࡶ࠶ࡿ㸧 2. ᑠ⬻ᛶᵓㄒ㞀ᐖ࣭ὶᾝ

3. ║⌫㐠ືࡢኻ⾜ࠊ║᣺

4. ⯙㋃⑓࢔ࢸࢺ࣮ࢮ㸦඲౛࡛ࡣ࡞࠸㸧 5. ప⥭ᙇᛶ㢦ㇺ

6. ║⌫⤖⭷࣭⓶⭵ࡢẟ⣽⾑⟶ᣑᙇ 6ṓࡲ࡛࡟50㸣ࠊ8ṓ᫬࡛90%ࡀ࠶ࡁࡽ࠿࡟࡞ࡿࠋ 7. ච␿୙඲⑕≧㸦཯᚟ᛶẼ㐨ឤᰁ⑕㸧 ణࡋ30%࡛ࡣච␿୙඲⑕≧ࢆㄆࡵ࡞࠸ࠋ 8. ᝏᛶ⭘⒆:≉࡟T⣽⬊ᛶ⭘⒆ࡢⓎ⏕㢖ᗘࡀ㧗࠸ࠋ

9. ࡑࡢ௚㸸Ⓨ⫱୙ⰋࠊෆศἪ␗ᖖ(⪏⢾⬟␗ᖖ㸸࢖ࣥࢫࣜࣥ㠀౫Ꮡᛶ⢾ᒀ⑓)ࠊ⓶⭵ࠊ㢌 㧥ࠊ⾑⟶ࡢ᪩⪁ᛶኚ໬

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␒㸧ࢆྵࡴ㌿ᗙࢆࡶࡘࣜࣥࣃ⌫ࡢฟ⌧

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㟁㞳ᨺᑕ⥺㧗ឤཷᛶ

ᇵ㣴⣽⬊࡟࠾ࡅࡿᨺᑕ⥺䛻䜘䜛ᰁⰍయ᩿⿣䛾ஹ㐍䚸⏕Ꮡ⬟䛾పୗ

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1. ᑠ⬻ኻㄪ࠿ࡽࡢㄗᄟᛶ⫵⅖ࠊච␿୙඲࡟ࡼࡿ㔜⠜࡞ឤᰁ⑕ࠊ໬Ꮫ⒪ἲ⸆㸦ᢠࡀࢇ๣㸧

ࡸᨺᑕ⥺἞⒪࡟㝿ࡋ࡚ࡢ㔜⠜࡞๪స⏝࡞࡝ࡀၥ㢟࡜࡞ࡿࠋ

'デ᩿ࡢ㐍ࡵ᪉㸦ࣇ࣮ࣟࢳ࣮ࣕࢺཧ↷㸧

㐍⾜ᛶࡢᑠ⬻ኻㄪࡀ࠶ࡾࠊ⾑ΎȘࣇ࢙ࢺࣉࣟࢸ࢖ࣥ㧗್ࢆ♧ࡍሙྜࠊᮏ⑌ᝈࡢྍ⬟ᛶࡀ㧗

࠸ࠋ⣽⬊ࢆ⏝࠸ࡓ$70ࢱࣥࣃࢡ㉁ࡢⓎ⌧ゎᯒࠊ㑇ఏᏊゎᯒ࡛☜ᐃデ᩿ࡀ࡛ࡁࡿࠋ

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⏨ᛶࡶࡋࡃࡣዪᛶࡢᝈ⪅࡛ࠊ㐍⾜ᛶᑠ⬻ኻㄪࠊᇵ㣴⣽⬊࡟࠾ࡅࡿᨺᑕ⥺࡟ࡼࡿᰁⰍయ᩿⿣

ࡢஹ㐍ࠊ⏕Ꮡ⋡ࡢపୗࠊATM㑇ఏᏊࡢ୧࢔ࣞࣝࡢᶵ⬟୙඲ᆺࡢኚ␗ࡀ࠶ࡿࡶࡢ デ᩿ࢆᙉࡃ␲࠺⑕౛

⏨ᛶࡶࡋࡃࡣዪᛶࡢᝈ⪅࡛ࠊ㐍⾜ᛶᑠ⬻ኻㄪࡀ࠶ࡾ௨ୗࡢ࠺ࡕ3ࡘࢆ‶ࡓࡍࡶࡢࠊ

║⌫ࡲࡓࡣ㢦㠃ࡢẟ⣽⾑⟶ᣑᙇ

⾑ΎIgAࡢṇᖖ್࠿ࡽࡢ-2SD௨ୖࡢపୗ

Șࣇ࢙ࢺࣉࣟࢸ࢖ࣥࡢṇᖖ್࠿ࡽࡢ-2SD௨ୖࡢୖ᪼

ᇵ㣴⣽⬊࡟࠾ࡅࡿᨺᑕ⥺࡟ࡼࡿᰁⰍయ᩿⿣ࡢஹ㐍ࠊ⏕Ꮡ⋡ࡢపୗ

デ᩿ࢆ␲࠺⑕౛

⏨ᛶࡶࡋࡃࡣዪᛶࡢᝈ⪅࡛ࠊ㐍⾜ᛶᑠ⬻ኻㄪࡀ࠶ࡾ௨ୗࡢ࠺ࡕ1ࡘࢆ‶ࡓࡍࡶࡢࠊ

║⌫ࡲࡓࡣ㢦㠃ࡢẟ⣽⾑⟶ᣑᙇ

⾑ΎIgAࡢṇᖖ್࠿ࡽࡢ-2SD௨ୖࡢపୗ

Șࣇ࢙ࢺࣉࣟࢸ࢖ࣥࡢṇᖖ್࠿ࡽࡢ-2SD௨ୖࡢୖ᪼

ᇵ㣴⣽⬊࡟࠾ࡅࡿᨺᑕ⥺࡟ࡼࡿᰁⰍయ᩿⿣ࡢஹ㐍ࠊ⏕Ꮡ⬟ࡢపୗ

)㚷ูデ᩿

௨ୗࡢ⑌ᝈࢆ㚷ูࡍࡿࠋ

ࢼ࢖࣑࣮᩿࣊ࣥ⿣⑕ೃ⩌ࠊࣈ࣮࣒ࣝ⑕ೃ⩌ࠊẟ⣽⾑⟶ᣑᙇᛶᑠ⬻ኻㄪ⑕ᵝ⑌ᝈ㸯ᆺࠊ2ᆺࠊ

║⌫㐠ືኻ⾜ࢆక࠺ኻㄪ⑕1ᆺࠊ2ᆺ

*㑇ఏᏛⓗ᳨ᰝ ATM㑇ఏᏊࡢኚ␗

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࠙἞⒪࣭⒪⫱ࡢᡭᘬࡁࠚ A. 㑇ఏ࢝࢘ࣥࢭࣜࣥࢢ

A-TࡣᖖᰁⰍయຎᛶᛶ㑇ఏ࡛Ⓨ⑕ࡍࡿࠋA-T ࡢྠ⬊ࢆᣢࡘ୧ぶࡣࠊḟᏊࢆ࡝࠺ࡍࡿ࠿ࠊ⮫

ᗋ㑇ఏᑓ㛛་࡜┦ㄯࡋỴࡵࡿࡇ࡜ࡀᮃࡲࡋ࠸ࠋ

ಖᅉ⪅ࡀ௚ࡢಖᅉ⪅࡜⤖፧ࡍࡿ☜❧ࡣ⣙1/200࡛࠶ࡾࠊࡇࡢA-Tಖᅉ⪅ྠኈࡢ࢝ࢵࣉࣝ࡟

A-TࡢᏊ౪ࡀ⏕ࡲࢀࡿ☜❧ࡣࡸࡣࡾ1/4࡛ࡍ࡜࡞ࡿࠋࡇࡇ࠿ࡽィ⟬ࡍࡿ࡜A-Tᝈ⪅ࡢ඗ᘵ ጜጒࡸ࠾ࡌࠊ࠾ࡤࡀA-Tಖᅉ⪅࡜⤖፧ࢆࡋ࡚ࠊࡉࡽ࡟A-TࡢᏊ౪ࡀ࡛ࡁࡿ☜❧ࡣ⣙1/1200

࡜࡞ࡿࠋᏊ౪ࡀ῝้࡞㞀ᐖࢆᢪ࠼࡚⏕ࡲࢀࡿࣜࢫࢡࡀ 1% ࡛࠶ࡿࡇ࡜࡜ẚ㍑ࡋ࡚ࠊᑠࡉ࡞

ᩘᏐ࡜⪃࠼ࡽࢀࠊ୍⯡ࡢே࡟ᑐࡋA-Tಖᅉ⪅࡛࠶ࡿࡢ࠿ࢆᑜࡡࡿࡇ࡜ࡣ㠀ᖖ࡟ᅔ㞴࡛࠶ࡾࠊ

✚ᴟⓗ࡟ಖᅉ⪅デ᩿ࢆ⾜࠺ᚲ↛ᛶࡣᑡ࡞࠸࡜⪃࠼ࡿࠋ B. ⚄⤒⑕≧

A-T ᝈ⪅ࡉࢇࡢ㐠ື㞀ᐖ࡟᭷ຠ࡞⸆≀ࡣ࡞࠸ࠋᑡ㔞ࢹ࢟ࢧ࣓ࢱࢰࣥࡢ᭷ຠᛶࢆ♧၀ࡍࡿㄽ

ᩥࡀ࠸ࡃࡘ࠿ሗ࿌ࡉࢀ࡚࠸ࡿࠋ㛗ᮇᢞ୚ࡀᚲせ࡛࠶ࡾࠊࢫࢸࣟ࢖ࢻࡢ๪స⏝ࡀၥ㢟࡜࡞ࡿࠋ ࡇࡢ๪స⏝ࢆ㍍ῶࡍࡿ┠ⓗ࡛ࢹ࢟ࢧ࣓ࢱࢰࣥࢆ㉥⾑⌫࡟ྲྀࡾ㎸ࡲࡏࠊᢞ୚ࡍࡿヨࡳࡀ࡞ࡉ

ࢀ࡚࠸ࡿࠋᇶᗏ᰾⑕≧࡟ᑐࡋ࡚L-DOPAࡸ࢔࣐ࣥࢱࢪࣥࡢ᭷ຠ౛ࡀሗ࿌ࡉࢀ࡚࠸ࡿࠋ C. ච␿

A-Tᝈ⪅ࡢ࠺ࡕ࠾࠾ࡼࡑ13ࡢᝈ⪅࡟ࡣࠊIgAࠊIgG2Ḟᦆࡀㄆࡵࡽࢀࡿࠋ⥲IgGࣞ࣋ࣝࡀ 500mg/dLࡢேࡣ 10-20%⛬ᗘ࡛࠶ࡿࠋ⣙80㸣࡛ CD3㝧ᛶT⣽⬊ᩘࡀ1000/Ǎl࡛࠶ࡾࠊ CD3㝧ᛶT⣽⬊ᩘࡀ450/Ǎl௨ୗ࡛㔜⑕ឤᰁ⑕ࢆྜేࡋࡸࡍ࠸࡜⪃࠼ࡽࢀࡿࠋ

ឤ ᰁ ⑕ ࡢ ㉳ ᅉ ⳦ ࡜ ࡋ ࡚ ࡣ ୖ Ẽ 㐨 ࠊ ୗ Ẽ 㐨 ឤ ᰁ ⑕ ࡜ ࡋ ࡚ Pseudomonas aeruginosaࠊ +aemoShilus inIluen]aࠊStreptococcus pneumoniaeࠊStaph\lococcus aureus࡞࡝ࡀከ

࠸ࠋࡲࡓEB࢘࢖ࣝࢫࡢ୙㢧ᛶࡢᣢ⥆ឤᰁࡢ࠶ࡿ⑕౛ࡀᏑᅾࡍࡿࠋ

⥲IgGࣞ࣋ࣝࡀ500mg/dL௨ୗࡢ⑕౛࡟ᑐࡋ࡚ච␿ࢢࣟࣈࣜࣥࡢᐃᮇ⿵඘ࡀ⾜ࢃࢀࡿࢣ࣮

ࢫࡀከ࠸ࠋ୍ᐃࡢ᭷ຠᛶࡀ࠶ࡿ࡜⪃࠼ࡽࢀࡿࡀࠊࡇࢀࡲ࡛ẚ㍑ヨ㦂ࡣ⾜ࢃࢀ࡚࠸࡞࠸ࠋ᭱

㏆࡛ࡣ⓶ୗᢞ୚ᆺච␿ࢢࣟࣈࣜࣥ〇๣ࡢ౑⏝ࡶ⾜ࢃࢀ࡚࠸ࡿࠋឤᰁண㜵࡜ࡋ࡚ࡢ ST ྜ๣

ࡸᢠ┿⳦⸆ࡢᢞ୚ࡀ⾜ࢃࢀࡿ⑕౛ࡶ࠶ࡿࡀࠊ᭷⏝ᛶࡣ᫂ࡽ࠿࡜࡞ࡗ࡚ࡣ࠸࡞࠸ࠋA-T ᝈ⪅

࡛ࡣ࢝ࣜࢽ⫵⅖ࡢሗ࿌ࡣ࡞࠸ࠋ

ච␿ᶵ⬟ࡀṇᖖ࡞ࡽࡤࠊᐃᮇⓗ࡟⾜ࢃࢀࡿᑠඣ⏝ண㜵᥋✀ࡣ඲࡚ (4✀ΰྜࠊ⫵⅖⌫⳦ࠊ࢖

ࣥࣇ࢚ࣝࣥࢨᱰ⳦ࠊ㯞⑈ࠊ࠾ࡓࡩࡃ࠿ࡐࠊ㢼⑈ࠊỈ①) ᥋✀ࡍࡿࠋࡲࡓᝈ⪅࡜ࡑࡢᐙ᪘ࡣ࢖

ࣥࣇ࢚ࣝࣥࢨ࣡ࢡࢳࣥࢆẖ⛅ࠊ᥋✀ࡍࡿࠋ D. ࿧྾ჾ

A-Tᝈ⪅ࡢ⣙80㸣ࡀఱࡽ࠿ࡢ࿧྾ჾឤᰁ⑕ࢆ⤒㦂ࡍࡿ࡜࠸ࢃࢀ࡚࠸ࡿࠋ25㸣ࡢ⑕౛࡛㛫㉁

ᛶ⫵⅖࡞࡝៏ᛶ࿧྾ჾ⑌ᝈࡀṚᅉ࡜࡞ࡗ࡚࠸ࡿࠋࡇ࠺࠸ࡗࡓ⑕౛࡛ࡣࢫࢸࣟ࢖ࢻࡢᢞ୚ࡀ

⾜ࢃࢀࠊ⑕≧ࡢᨵၿࢆぢࡿࡀࠊ㛗ᮇⓗ࡟ࡣ⏕Ꮡ⋡ࡢᨵၿ࡟ࡣࡘ࡞ࡀࡽ࡞࠸ࠋ࿧྾ࡀὸ࠸ࠊ

࠶ࡿ࠸ࡣတࡀ࠺ࡲࡃ࡛ࡁ࡞࠸ࡼ࠺࡞ᝈ⪅࡟ࡣẼ㐨ࢡࣜ࢔ࣛࣥࢫ⏝ࡢჾල (ࣂ࢖ࣈ࣮ࣞࢱࠊ

⬚ቨ࡟㧗᣺ືࢆ୚࠼ࡿჾලࠊ⑱㝖ཤࢆ⿵ຓࡍࡿჾල)ࠊ⬚㒊⌮Ꮫ⒪ἲࠊࢫࢸࣟ࢖ࢻ⸆ࡢ྾ᘬࠊ Ẽ⟶ᨭᣑᙇ๣࡟ࡼࡿࢧ࣏࣮ࢺࡀ㔜せ࡜ᛮࢃࢀࡿࠋ

A-T ᝈ⪅ࡀ៏ᛶⓗ࡞⫵⑌ᝈࢆᝈࡗ࡚࠸ࡿሙྜࠊ࢔ࢪࢫ࣐ࣟ࢖ࢩࣥ࡞ࡢ࡝ண㜵ⓗ࡞ᢠ⳦⸆ࡢ

౑⏝࡟ࡼࡾ⣽⳦ᛶ⫵⅖ࡸẼ⟶ᨭᣑᙇ⑕ࡢࣜࢫࢡࢆᢚ࠼ࡿࡇ࡜ࡀ࡛ࡁࡿ࠿ࡶࡋࢀ࡞࠸ࠋ E

E. ᰤ㣴

A-T ᝈ⪅ࡢከࡃ࡟పᰤ㣴ࡀㄆࡵࡽࢀࡿࠋࡲࡓᄟୗ㞀ᐖ࡟ࡼࡾ⡆༢࡟ㄗᄟᛶ⫵⅖ࢆᘬࡁ㉳ࡇ ࡍࠋࡇࢀࢆᅇ㑊ࡍࡿࡓࡵ࡟ࠊ㣗஦ᅇᩘࢆከࡃࡋࠊ㢌ࡢ఩⨨࡟Ẽࢆ௜ࡅṇࡋ࠸ጼໃ࡛㣗஦ࢆ

⾜ࢃࡏࡿࠋ㣗ရ࡟ࡼࡗ࡚ࡣ࡜ࢁࡳࢆࡘࡅࡿࡇ࡜࡛ㄗᄟࡢࣜࢫࢡࢆపῶ࡛ࡁࡿࠋ F. ⢾ᒀ⑓࣭⬡㉁௦ㅰ␗ᖖ

A-Tࡢ30㸣࡟⢾ᒀ⑓ࡢⓎ⑕ࢆࡳ࡜ࡵࡿࠊከࡃࡣ2ᆺ⢾ᒀ⑓࡛࠶ࡿࡀࠊ1ᆺ⢾ᒀ⑓ࡢሗ࿌ࡶ

࠶ࡿࠋ⾑⢾್ࠊ⬡㉁௦ㅰ␗ᖖ࡟ࡓ࠸ࡋ࡚ࠊᑐ⑕ⓗ࡟⾑⢾㝆ୗ๣ࠊ⬡㉁ᨵၿ⸆ࢆᢞ୚ࡍࡿࠋ G. ᝏᛶ⭘⒆

A-T ࡢ 20-30㸣࡟ᝏᛶ⭘⒆ࡢྜేࢆㄆࡵࡿࠋ㏻ᖖࡢ໬Ꮫ⒪ἲ࡛ࡣẘᛶࡀᙉࡃࠊ⏝㔞ࢆῶ㔞

ࡋࡓ໬Ꮫ⒪ἲࡀᚲせ࡜࡞ࡿࠋ

໬Ꮫ⒪ἲ࡟࠾ࡅࡿ἞⒪⸆㑅ᢥࡢ࢞࢖ࢻࣛ࢖ࣥ:

1) A-Tࡢᝈ⪅ࡣᨺᑕ⥺࡟㧗ឤཷᛶࢆ♧ࡍࠋᨺᑕ⥺ࢆ⏝࠸ࡓ἞⒪ࡣྍ⬟࡞㝈ࡾ㑊ࡅࡿ࡭ࡁ࡜

⪃࠼ࡿࠋྠᵝ࡟ࠊᨺᑕ⥺㢮ఝࡢస⏝ࢆ♧ࡍ⸆๣ࣈ࣐ࣞ࢜࢖ࢩࣥ࡞࡝ࡢ౑⏝ࡶ㑊ࡅࡿ࡭ࡁ࡛

࠶ࡿࠋࡶࡋࠊᨺᑕ⥺⒪ἲࡀᚲ㡲࡜⪃࠼ࡽࢀࡿሙྜ࡟ࡣࠊ༑ศ࡞ῶ㔞(༴㝤㔞ࡢ1/3⛬ᗘ)ࡀᚲ せ࡛࠶ࡿࠋ

2) A-Tࡢᝈ⪅ࡣ㐠ືኻㄪࢆక࠺ࡇ࡜࠿ࡽࠊࣅࣥࢡࣜࢫࢳࣥࡢ⚄⤒ẘᛶ࡟ࡼࡿ➽ຊపୗ࠿ࡽ

ࡢᅇ᚟ࡀᅔ㞴࡛࠶ࡿࠋࡇࡢࡓࡵࠊẖ㐌ࡢࣅࣥࢡࣜࢫࢳࣥᢞ୚ࡣ⪏࠼ࡽࢀ࡞࠸࡜⪃࠼ࡿࠋᢞ

୚ᚋ࡟➽ຊపୗࡢᚩೃࡀ⌧ࢀࡓሙྜ࡟ࡣࠊ௨㝆ࡢᢞ୚࡟ࡘ࠸࡚୰Ṇࡶࡋࡃࡣῶ㔞ࢆ⾜࠺࡭

ࡁ࡛࠶ࡿࠋࣅࣥࣈࣛࢫࢳࣥࡣࣅࣥࢡࣜࢫࢳࣥࡼࡾࡶ⚄⤒ẘᛶࡀ㍍ᚤ࡜⪃࠼ࡽࢀࠊࡼࡾᏳ඲

࡟౑⏝ྍ⬟࡜⪃࠼ࡿࠋ἞⒪ࣞࢪ࣓࡟ẖ㐌ࡢࣅࣥࢡࣜࢫࢳࣥᢞ୚ࡀィ⏬ࡉࢀ࡚࠸ࡿሙྜ࡟ࡣࠊ

ࣅࣥࣈࣛࢫࢳ࡛ࣥ௦᭰ࡍ࡭ࡁ࡛࠶ࡿࠋࣅࣥࢡࣜࢫࢳࣥ 1.5 mg/m2 ࡣࣅࣥࣈࣛࢫࢳࣥ 6

mg/m2࡟⨨ࡁ᥮࠼ྍ⬟࡛࠶ࡿࠋ࡞࠾ࠊ⤒㦂ࡀ࡞࠸ࡓࡵ᥎ ࡢᇦࢆฟ࡞࠸ࡀࠊࢿࣛࣛࣅࣥࡶ

⚄⤒ẘᛶࢆ᭷ࡍࡿࡇ࡜࠿ࡽࠊA-T ࡢᝈ⪅࡛ࡣẘᛶࡀቑᙉࡍࡿྍ⬟ᛶࡀ࠶ࡿࠋ㐺ᛂࡣᢞ୚࡟

ࡼࡿ฼┈ࢆ⪃࠼ៅ㔜࡟Ỵᐃࡉࢀࡿ࡭ࡁ࡜⪃࠼ࡿࠋ

3) A-Tࡢᝈ⪅ࡣẟ⣽⾑⟶ᣑᙇࡢᏑᅾ࠿ࡽࡶ♧၀ࡉࢀࡿࡼ࠺࡟ࠊࢩࢡࣟࣇ࢛ࢫࣇ࢓࣑ࢻࡲࡓ

ࡣ࢖ࣇ࢛ࢫࣇ࢓࣑ࢻ࡟ࡼࡿฟ⾑ᛶ⭤⬔⅖ࡢⓎ⑕ࣜࢫࢡࡀ㧗࠸࡜⪃࠼ࡿࠋ᭦࡟ࠊA-T ࡢᝈ⪅

࡛ࡣࠊᢞ୚ᚋᩘ࢝᭶ࡓࡗ࡚⌧ࢀ࡚ࡃࡿྍ⬟ᛶࡶ࠶ࡿࠋࡋࡓࡀࡗ࡚ࠊᢞ୚㔞࡟࠿࠿ࢃࡽࡎࠊ

༑ศ࡞㍺ᾮ࡜࣓ࢫࢼࡢᢞ୚ࡀᚲせ࡛࠶ࡿࠋࡲࡓࠊࡇࢀࡽ࢔ࣝ࢟ࣝ໬๣࡟ᑐࡋ࡚ࡶA-Tࡢᝈ

⪅ࡣ㧗ឤཷᛶࢆ♧ࡍࡇ࡜࠿ࡽࠊ2/3࠿ࡽ1/2⛬ᗘ࡬ࡢῶ㔞ࡀᚲせ࡜⪃࠼ࡽࢀࡿࠋ

4) A-Tࡢᝈ⪅࡟࣓ࢺࢺࣞ࢟ࢧ࣮ࢺࢆ౑⏝ࡋࡓሙྜ࡟ࠊ㔜⠜࠿ࡘ㞴἞ᛶࡢᾘ໬⟶⢓⭷㞀ᐖࡀ

㉳ࡇࡾࠊ⒕⑞ᙧᡂࠊ⊃✽ࢆ㉳ࡇࡍࡇ࡜ࡀ⤒㦂ࡉࢀࡿࠋࡑࢀࡺ࠼ࠊ࣓ࢺࢺࣞ࢟ࢧ࣮ࢺ⾑୰⃰

ᗘࣔࢽࢱࣜࣥࢢࠊࣟ࢖ࢥ࣎ࣜࣥࡢᢞ୚ࢆィ⏬ⓗ࡟⾜࠸ࠊ⸆๣ࡢయእ᤼ἥࢆ㏿ࡸ࠿ㄏᑟࡍࡿ

ᚲせࡀ࠶ࡿࠋࡍ࡞ࢃࡕࠊ༑ศ࡞㍺ᾮࠊ㐺ษ࡞ᒀࡢ࢔ࣝ࢝ࣜ໬ࠊ⭈㞀ᐖᛶࡢ࠶ࡿ⸆๣ᢞ୚ࡢ ᅇ㑊࡟ࡘ࠸࡚ࠊ㓄៖ࡍ࡭ࡁ࡛࠶ࡿࠋ

5) A-Tࡢᝈ⪅ࡣࠊ࢚ࢺ࣏ࢩࢻࡸࢻ࢟ࢯࣝࣅࢩࣥ࡞࡝ࡢࢺ࣏࢖ࢯ࣓࣮ࣛࢮ㜼ᐖ๣࡟ᑐࡍࡿ㧗

ឤཷᛶࡀ࠶ࡿࠋSt. Jude ᑠඣ◊✲⑓㝔࡟࠾ࡅࡿ἞⒪ᣦ㔪࡛ࡣࠊ἞⒪཯ᛂᛶࡀ୙Ⰻ࡛࡞࠸ሙ

ྜ࡟ࡣ 3/4 ⛬ᗘ࡟ῶ㔞ࡋ࡚ᢞ୚ࡍࡿࡇ࡜ࢆ᥎ዡࡋ࡚࠸ࡿࠋࡋ࠿ࡋ⣽⬊⏕≀Ꮫⓗ࡟ࠊA-T ࡢ ᝈ⪅ࡣ᫂ࡽ࠿࡟ࡣ࢚ࢺ࣏ࢩࢻࡸࢻ࢟ࢯࣝࣅࢩࣥ࡟ᑐࡍࡿ㧗ឤཷᛶࡀ࠶ࡾࠊ᭱㏆ࡢᑠඣᛴᛶ

ࣜࣥࣃᛶⓑ⾑⑓ࡢ἞⒪࡟࠾࠸࡚ࡣ஧ḟࡀࢇ࡞࡝Ⓨࡀࢇࡢࣜࢫࢡࡶ⪃៖ࡋ࡚ࠊྍ⬟࡞㝈ࡾᢞ

୚ࢆ㑊ࡅࡿ᪉ྥ࡟ࡍࡍࢇ࡛࠾ࡾࠊྍ⬟࡛࠶ࢀࡤࢺ࣏࢖ࢯ࣓࣮ࣛࢮ㜼ᐖ๣ࢆྵࡲ࡞࠸἞⒪ィ

⏬ࢆ❧࡚ࡿ࡭ࡁ࡜⪃࠼ࡿࠋ

6) ࣜࢶ࢟ࢩ࣐ࣈ࡞࡝ศᏊᶆⓗ⸆ࡢ౑⏝ࢆ✚ᴟⓗ࡟⪃៖ࡍࡿࠋ ࡀࢇ໬Ꮫ⒪ἲ᫬ࡢࢧ࣏࣮ࢺࢣ࢔

࣭ࢲࣈ࣮࣓ࣝࣝࣥࡢ୰ᚰ㟼⬦࢝ࢸ࣮ࢸࣝࢆ␃⨨ࡋࠊᏳ඲࡞⸆๣ᢞ୚ࠊ༑ศ࡞ᰤ㣴ࡢ⿵⤥ࢆ

⾜࠺ࠋ

ᰤ㣴ࡢ⟶⌮࡟༑ศ࡞㓄៖ࢆ⾜࠺ࠋA-T ࡢᝈ⪅ࡣ໬Ꮫ⒪ἲ࡟ࡼࡿయ㔜ῶᑡࡀⴭ࡛᫂࠶ࡾᅇ᚟

ࡀ㞴ࡋ࠸ࠋ

࣭἞⒪ࡢ๓࡟⬻MRIࡢ᧜ᙳ࡜ࠊᑠඣ⚄⤒⛉་࡟ࡼࡿデᐹࢆཷࡅࡿ࡭ࡁ࡛࠶ࡿࠋ

࣭Ⓨ⇕᫬࡟ࡣዲ୰⌫ῶᑡࡢ᭷↓࡟㛵ࢃࡽࡎࠊࡲࡓⓎ⇕ࡀ࡞ࡃ࡚ࡶ඲㌟≧ែⰋዲ࡛࡞࠸ሙྜ

࡟ࡣࠊ㏿ࡸ࠿࡟⾑ᾮᇵ㣴ࢆᐇ᪋ࡋࠊᗈᇦࢫ࣌ࢡࢺ࣒ࣛࢆ᭷ࡍࡿᢠ⳦⸆ࢆᢞ୚ࡍࡿ࡭ࡁ࡛࠶

ࡿࠋ

࣭A-Tࡢᝈ⪅࡛ࡣࠊX⥺᧜ᙳ࡞࡝ᨺᑕ⥺デ᩿ࡣ㑊ࡅࡿ࡭ࡁ࡛࠶ࡾࠊྍ⬟࡞㝈ࡾMRIࡸ㉸㡢 Ἴ᳨ᰝ࡛௦⏝ࡍ࡭ࡁ࡛࠶ࡿࠋࡋ࠿ࡋX⥺デ᩿࡟ࡼࡾ᭷⏝࡞᝟ሗࡀᚓࡽࢀࡿ࡜ุ᩿ࡋࡓ࡜ࡁ ࡣࠊ⾜࠺࡭ࡁ࡛࠶ࡿࠋ

࣭STྜ๣ࡢண㜵ᢞ୚ࢆ⾜࠺

࣭H2ࣈࣟࢵ࣮࢝ࡶࡋࡃࡣࣉࣟࢺ࣏ࣥࣥࣉ㜼ᐖ๣ࡢண㜵ᢞ୚ࢆ⾜࠺ࠋ

࣭ච␿ࢢࣟࣈࣜࣥࡢ⿵඘⒪ἲࢆ⾜࠺ࠋ

࣭㛗ᮇ⮩ᗋ࡟ࡼࡿ➽ຊపୗࠊṌ⾜ᅔ㞴ࡀⴭ᫂࡟ฟ⌧ࡋ࡚ࡃࡿࡢ࡛ࠊ✚ᴟⓗ࡞ࣜࣁࣅࣜࢸ࣮

ࢩࣙࣥࢆ⾜࠺ ࠋ H

H. ච␿୙඲⑕ࠊᝏᛶ⭘⒆ࢆⓎ⑕ࡋࡓᝈ⪅ࡢ㐀⾑⣽⬊⛣᳜

AT࡜ࡑࡢ㢮⦕⑌ᝈࡢ㐀⾑ᖿ⣽⬊⛣᳜ࡣࠊ๓ฎ⨨ẘᛶࡢᙉࡉ࡜ࠊ㐀⾑ᖿ⣽⬊⛣᳜࡛ࡣ἞⒵ࡋ

࠼࡞࠸඲㌟ྜే⑕ࡢᏑᅾ࠿ࡽᩗ㐲ࡉࢀ࡚࠾ࡾࠊሗ࿌ࡣ㝈ࡽࢀ࡚࠸ࡿࠋ

European Society Ior Blood and MarroZ Transplantation㸦EBMT㸧ࡣࠊ4౛ࡢAT࡟ ᑐࡋ࡚㦵㧊◚ቯⓗ๓ฎ⨨㸦MAC㸧ࢆ⏝࠸ࡓ㐀⾑ᖿ⣽⬊⛣᳜ࢆ⾜࠸ࠊ⏕Ꮡࡣ㸯ྡࡢࡳ࡛࠶ࡗ ࡓࠋ௨㝆ࡣࠊࡑࡢX⥺㧗ឤཷᛶࡼࡾTBIࡀ┬࠿ࢀࠊ௚ࡢᰁⰍయ୙Ᏻᐃᛶࢆࡶࡘ⑌ᝈྠᵝࠊ 㦵㧊◚ቯⓗ๓ฎ⨨㸦RIC㸧࡟ࡼࡿ⛣᳜ࡀ୺య࡜࡞ࡗ࡚࠸ࡿࠋ

RalI SchuEertࡽࢻ࢖ࢶ࡛ࡣࠊ㔜⑕ච␿୙඲ࢆక࠺4ṓࡢAT࡟๓ฎ⨨Flu㸩CY㸩ATG

ࢆ⏝࠸ࠊ⛣᳜ᚋ3ᖺ࡛⏕Ꮡࢆ☜ㄆࡋ࡚࠸ࡿࠋࡲࡓ8ssoZic] Mࡽ࣏࣮ࣛࣥࢻ࠿ࡽࡢሗ࿌࡛

ࡣࠊALLࢆⓎ⑕ࡋࡓ3ṓ⏨ඣ࡟໬Ꮫ⒪ἲᚋ࡟ᮎᲈ⾑ᖿ⣽⬊⛣᳜ࢆ⾜࠸ࠊ6ᖺ௨ୖࡢ↓⑓⏕

Ꮡࢆᯝࡓࡋ࡚࠸ࡿࠋ๓ฎ⨨ࡣ BU㸩FLU㸩ATG-FreseniusࠊGVHDண㜵ࡣ CsAࠊMTXࠊ OKT-3࡛⾜࠸ࠊ4ᅇࡢࢻࢼ࣮ࣜࣥࣃ⌫㍺ὀ㸦DLI㸧ࡀ㏣ຍࡉࢀࡓࠋ2012ᖺGhosh Sࡽࡣࠊ ATデ᩿๓࡟㧗IgM⑕ೃ⩌࡜ࡋ࡚ࠊ๓ฎ⨨treosulIan㸩FLU㸩ATG-Freseniusࢆ⏝࠸࡚㦵 㝶⛣᳜ࢆ⾜ࡗࡓࠋ⛣᳜ᚋ8ࣨ᭶࡟EBVࣜࣥࣃቑṪᛶ⑌ᝈ㸦EBV-LPD㸧ࢆⓎ⑕ࡋṚஸࡋࡓ ࡀࠊ᏶඲࣓࢟ࣛࢆ㐩ᡂࡋ୍ᗘࡣ㏥㝔࡛ࡁ࡚࠸ࡿࠋࢻࢼ࣮ࡣ࠸ࡎࢀࡶHLA୍⮴⾑⦕࡛ࠊ඲౛

⏕╔ࡋ࡚࠸ࡓࠋAT࡟࠾࠸࡚ࠊ㦵㧊◚ቯⓗ๓ฎ⨨㸦RIC㸧ࡢ๓ฎ⨨ẘᛶࡀ⮴࿨ⓗ࡜࡞ࡗࡓ⑕

౛ࡣ࡞࠿ࡗࡓࠋ

デ⒪࢞࢖ࢻࣛ࢖ࣥ㻌㻌

ࣈ࣮࣒ࣝ㸦 Bloom 㸧⑕ೃ⩌

㻌

㼍㻕㻌⑌ᝈᴫせ㻌

㻌 䝤䝹䞊䝮⑕ೃ⩌䛿䚸⏕ୗ᫬䛛䜙䛾ᑠ᯶䛺యᆺ䚸≉ᚩⓗ䛺㢦ㇺ䚸᪥ග㐣ᩄᛶ⣚ᩬ䚸ච␿୙඲

⑕䜢≉ᚩ䛸䛩䜛ᖖᰁⰍయຎᛶᙧᘧ䛾㑇ఏᛶ⑌ᝈ䛷䛒䜚䚸㻞㻜ṓ䜎䛷䛻䚸⣙㻟๭䛾⑕౛䛜䛺䜣䜙 䛛䛾ᝏᛶ⭘⒆䜢Ⓨ⑕䛩䜛䚹ጜጒ┦ྠᰁⰍయ䛾⤌䜏᥮䛘㻔㼟㼕㼟㼠㼑㼞㻌㼏㼔㼞㼛㼙㼍㼠㼕㼐㻌㼑㼤㼏㼔㼍㼚㼓㼑㻧㻌㻿㻯㻱㻕䛜㧗

⋡䛻ㄆ䜑䜙䜜デ᩿䛻㔜せ䛷䛒䜛䚹䠠䠪䠝䛾」〇䞉ಟ᚟䛻㛵୚䛩䜛䝦䝸䜹䞊䝊䝍䞁䝟䜽㻮㻸㻹 䜢䝁 䞊䝗䛩䜛㻮㻸㻹㑇ఏᏊ䛾␗ᖖ䛜ཎᅉ䛷䛒䜛䚹㻌

㻌

㼎㻕㻌␿Ꮫ㻌

㻌 㻞㻜㻝㻜ᖺᗘ䛻ᐇ᪋䛥䜜䛯඲ᅜㄪᰝ䛻䜘䜚䚸ᅜෆ䛷䛿㻥ᐙ⣔㻝㻜⑕౛䛾䝤䝹䞊䝮⑕ೃ⩌䛾☜ᐃ

౛䛜᫂䜙䛛䛸䛺䛳䛶䛔䜛䚹䜰䝅䝳䜿䝘䞊䝆⣔䝴䝎䝲ே䛷䛿䚸ಖᅉ⪅䛜⣙㻝㻜㻜ே䛻㻝ே䛾㢖ᗘ䛷 Ꮡᅾ䛩䜛䛸䛥䜜䛶䛔䜛䚹㻌

㻌

㼏㻕㻌デ᩿ᇶ‽䚸デ᩿䛾ᡭᘬ䛝㻔⮫ᗋ⑕≧䚸㌟యᡤぢ䚸᳨ᰝᡤぢ䚸≉Ṧ᳨ᰝ䚸㚷ู⑌ᝈ䛺䛹㻕㻌 㻌 㻌 㻭㻚㻌⮫ᗋ⑕≧㻌

㻝㻚㻌᪥ග㐣ᩄᛶ⾑⟶ᣑᙇᛶ⣚ᩬ䠄ከ䛟䛿㢋㒊䛻ᑐ⛠ᛶ䛻ฟ⌧䠅㻌 㻞㻚㻌ᑠ᯶䛺యᆺ䠄⏕ୗ᫬䛛䜙ㄆ䜑䜙䜜ᆒᩚ䛜䛸䜜䛶䛔䜛䠅㻌 㻟㻚㻌≉ᚩⓗ䛺㢦ㇺ䠄㫽ᵝ㢦ㇺ䠅㻌

㻠㻚㻌ච␿୙඲⑕䠄ᢠయ⏘⏕୙඲㻧㻌⾑Ύ㻵㼓㻹䚸㻵㼓㻭䛾పୗ䠅㻌

㻡㻚㻌ᝏᛶ⭘⒆㻔㐀⾑ჾ⭘⒆䚸⓶⭵⒴䚸኱⭠⒴䚸ங⒴➼㻕䛾ⱝᖺⓎ⑕䛜㧗⋡䛷䛒䜛㻌 㻢䠊㻵㻵ᆺ⢾ᒀ⑓䛾ྜే㻌

㻣䠊ᛶ⭢ᶵ⬟పୗ䠄↓⢭Ꮚ⑕䚸᪩ᮇ䛾㛢⤒䚸୙ዷ䠅㻌 㻌 㻌

㻌 㻮㻚㻌᳨ᰝᡤぢ㻌

㻝㻚㻌ᢠయ⏘⏕୙඲䠄ከ䛟䛿⾑Ύ㻵㼓㻹್䛜㻡㻜㼙㼓㻛㼐㼘䛾௨ୗ䛾ప್䜢♧䛩䠅㻌 㻞㻚㻌㼀⣽⬊䚸㻮⣽⬊ᩘ䛿ṇᖖ⠊ᅖ䛾䛣䛸䛜ከ䛔㻌

㻌㻌 㻯㻚㻌≉Ṧ᳨ᰝ㻌

㻝㻚㻌ጜጒᰁⰍศయ⤌䜏᥮䛘㻔㼟㼕㼟㼠㼑㼞㻌㼏㼔㼞㼛㼙㼍㼠㼕㼐㻌㼑㼤㼏㼔㼍㼚㼓㼑㻕䛾ஹ㐍㻌 㻞㻚㻌㻮㻸㻹㑇ఏᏊኚ␗㻌

㻌

㻌 㻰㻚㻌㚷ู⑌ᝈ㻌

㻌 㻾㼛㼠㼔㼙㼡㼚㼐㻙㼀㼔㼛㼙㼟㼛㼚⑕ೃ⩌䚸㻯㼛㼏㼗㼍㼥㼚㼑⑕ೃ⩌䚸㼃㼑㼞㼚㼑㼞⑕ೃ⩌䚸㻲㼍㼚㼏㼛㼚㼕⑕ೃ⩌䚸ẟ⣽⾑⟶

ᣑᙇᛶኻㄪ⑕䚸Ⰽ⣲ᛶ஝⓶⑕䚸ඛኳᛶゅ໬⑕㻌 ➼䛾㑇ఏᛶ㧗Ⓨ⒴⑕ೃ⩌䛜㚷ู⑌ᝈ䛸䛧䛶 ᣲ䛢䜙䜜䜛䚹㻾㼛㼠㼔㼙㼡㼚㼐㻙㼀㼔㼛㼙㼟㼛㼚 ⑕ೃ⩌䛸䛿䚸ᑠ᯶䛺యᆺ䚸᪥ග㐣ᩄᛶ⣚ᩬ䚸ከᙧ⓶⭵ⴎ⦰

⑕䚸㦵᱁␗ᖖ䚸ⱝᖺᛶⓑෆ㞀䜢≉ᚩ䛸䛧䚸㻰㻺㻭 䛾」〇䞉ಟ᚟䛻㛵୚䛩䜛䝦䝸䜹䞊䝊䝍䞁䝟䜽

㻾㻱㻯㻽㻸㻠 䛾␗ᖖ䛻䜘䜚Ⓨ⑕䛩䜛ᖖᰁⰍయຎᛶ㑇ఏ䛾⑌ᝈ䛷䛒䜛䚹䝤䝹䞊䝮⑕ೃ⩌䛸ྠᵝ䛻䚸

㧗⋡䛻ᝏᛶ⭘⒆㻔㦵⫗⭘䚸⓶⭵ᡥᖹୖ⓶⒴䚸ⓑ⾑⑓䚸⫶⒴䛺䛹㻕䜢Ⓨ⑕䛩䜛䚹ྠ䛨㈐௵㑇ఏᏊ 䛻␗ᖖ䜢᭷䛩䜛㢮⦕⑌ᝈ䛸䛧䛶䚸㻾㻭㻼㻭㻰㻵㻸㻵㻺㻻⑕ೃ⩌䚸㻮㼍㼘㼘㼑㼞㻙㻳㼑㼞㼛㼘㼐⑕ೃ⩌䛜䛒䜛䚹㻌 㻌

㻌 㻱㻚㻌デ᩿䛾ᡭᘬ䛝䠄䝣䝻䞊䝏䝱䞊䝖ཧ↷䠅㻌

㻌 ⏕ୗ᫬䛛䜙䛾ᑠ᯶䛺యᆺ䚸᪥ග㐣ᩄᛶ⣚ᩬ䚸Ⓨ⒴䛾᪤ 䛜䛒䜚䚸⾑Ύ 㻵㼓㻹 䛾ప್䛜䛒䜛ሙ

ྜ䚸ᮏ⑕䜢␲䛖䚹ጜጒᰁⰍศయ⤌䜏᥮䛘䜢ㄪ䜉ஹ㐍䛧䛶䛔䜛ሙྜ䛿ᬻᐃⓗ䛻ᮏ⑕䛸䛩䜛䚹᭱

⤊ⓗ䛻㻮㻸㻹㑇ఏᏊኚ␗䛜☜ㄆ䛷䛝䜜䜀☜ᐃデ᩿䛸䛺䜛䚹㻌

㻌 㻲㻚㻌デ᩿ᇶ‽㻌

㻌 ୖグ䛾⮫ᗋ⑕≧䛸᳨ᰝᡤぢ䜢‶䛯䛧䚸㻮㻸㻹 㑇ఏᏊኚ␗䛜䛒䜛ሙྜ䛻䝤䝹䞊䝮⑕ೃ⩌䛸デ

᩿䛩䜛䠄ᖖᰁⰍయຎᛶ㑇ఏ䠅䚹㻌 㼐

㼐㻕㻌ྜే⑕㻌

㻌 㻌 ᝏᛶ⭘⒆䛾㧗⋡䛺Ⓨ⑕䛜㝿䛰䛳䛯≉ᚩ䛷䛒䜛䚹㻞㻜ṓ䜎䛷䛻⣙㻟๭䛾ᝈ⪅䛜䛺䜣䜙䛛䛾ᝏ ᛶ⭘⒆䜢Ⓨ⑕䛩䜛䚹≉䛻 㻮 ⣽⬊⣔䝸䞁䝟⭘䛾Ⓨ⏕౛䛜ከ䛔䚹᫆ឤᰁᛶ䛻䜘䜛⫵⅖䛾ྜే䜒䚸

⏕࿨ணᚋ䜢ᕥྑ䛩䜛䚹㧗㢖ᗘ䛻⢾ᒀ⑓䜢ྜే䛩䜛䚹㻌 㻌

㼑㻕㻌㔜⑕ᗘศ㢮㻌

㔜⑕㻦㻌䝤䝹䞊䝮⑕ೃ⩌䛿䚸཯᚟ᛶឤᰁ䚸⢾ᒀ⑓䚸ᝏᛶ⭘⒆䛾Ⓨ⏕➼䛻䜘䜚ᐃᮇⓗ䛺἞⒪䛜 ᚲせ䛷䛒䜛䚹䜎䛯䚸ᐃᮇⓗ䛺඲㌟᳨⣴䛻䜘䜛ᝏᛶ⭘⒆䛾᪩ᮇⓎぢ䛜ᮏ⑌ᝈ䛾⟶⌮ୖ㔜せ䛷 䛒䜛䛯䜑䚸☜ᐃデ᩿౛䛿඲౛㔜⑕䛻ศ㢮䛩䜛䚹㻌

㻌

㼒㻕㻌⟶⌮᪉ἲ㻔䝣䜷䝻䞊䜰䝑䝥ᣦ㔪㻕䚸἞⒪㻌

㻌 ἞⒪䛿ᑐ⑕⒪ἲ䛜ᇶᮏ䛸䛺䜛䚹᫆ឤᰁᛶ䛻ᑐ䛧䛶䛿ᢠ⳦⸆䛻䜘䜛ண㜵ᢞ୚䜒⾜䜟䜜䜛䚹⓶

⭵⒴Ⓨ⏕䛾ண㜵䛾䛯䜑䚸᪥ගᭀ㟢䜢㑊䛡䛺䛡䜜䜀䛺䜙䛺䛔䚹ᝏᛶ⭘⒆䛾Ⓨ⏕䜢᪩ᮇ䛻Ⓨぢ 䛩䜛䛯䜑䛻⾑ᾮ᳨ᰝ㻔⭘⒆䝬䞊䜹䞊➼ྵ䜐㻕䚸ྛ✀⏬ീ᳨ᰝ䚸኱⭠ෆど㙾᳨ᰝ䚸⓶⭵⛉ᑓ㛛

་䛻䜘䜛デᐹ䜢ᐃᮇⓗ䛻⾜䛖ᚲせ䛜䛒䜛䚹䝤䝹䞊䝮⑕ೃ⩌䛷䛿ᨺᑕ⥺ឤཷᛶ䛾ஹ㐍䛜䜏䜙䜜 䜛ྍ⬟ᛶ䛜ᣦ᦬䛥䜜䛶䛔䜛䛯䜑⏬ീ᳨ᰝ䛿䚸㉸㡢Ἴ᳨ᰝ䚸㻹㻾㻵➼䛷⾜䛖䚹䜎䛯䚸ᢠ䛜䜣๣䛻ᑐ 䛩䜛ឤཷᛶ䛜ஹ㐍䛧䛶䛔䜛䛸⪃䛘䜙䜜䜛䛯䜑䚸㏻ᖖ䛾䝥䝻䝖䝁䞊䝹䛾༙㔞➼䛻ῶ㔞䛧䛶἞⒪䜢

⾜䛖䛣䛸䜒䛒䜛䚹⢾ᒀ⑓䛾ྜే㢖ᗘ䛜ከ䛔䛯䜑䚸ᐃᮇⓗ䛻㻴㼎㻭㻝㼏➼䜢☜ㄆ䛩䜛䚹㻌 㻌

㼓㻕㻌ணᚋ䚸ᡂேᮇ䛾ㄢ㢟㻌

㻌 㻞㻜㻝㻜ᖺᗘ䛻ᐇ᪋䛥䜜䛯ᮏ㑥䛻䛚䛡䜛㞟ィ䛷䛿䚸㻝㻜⑕౛୰㻠౛䛜䚸䛭䜜䛮䜜㻣ṓ䚸㻞㻟ṓ䚸㻞㻤

ṓ䚸㻟㻣 ṓ䛷Ṛஸ䛧䛶䛔䛯䚹ணᚋ䛿䚸ྜే⑕㻔୺䛻ᝏᛶ⭘⒆㻕䛾᭷↓䛻ᕥྑ䛥䜜䜛䛜䚸ẚ㍑ⓗⱝ ᖺ䛷ᝏᛶ⭘⒆䜢Ⓨ⑕䛧䚸⮴Ṛⓗ䛸䛺䜛䛣䛸䛜ከ䛔䚹㻌

㻌

㼔㻕㻌デ⒪ୖὀព䛩䜉䛝Ⅼ㻌

㻌 ᝏᛶ⭘⒆䛾Ⓨ⏕䛻ᖖ䛻␃ព䛩䜛ᚲせ䛜䛒䜛䚹䜎䛯䚸ᨺᑕ⥺ឤཷᛶ䛾ஹ㐍䛜䜏䜙䜜䜛ྍ⬟ᛶ 䛜ᣦ᦬䛥䜜䛶䛔䜛䛯䜑䚸⏬ീ᳨ᰝ➼䛾᪋⾜᫬䛻䛿ὀព䛜ᚲせ䛷䛒䜛䚹㻌

㻌

ཧ

ཧ⪃ᩥ⊩㻌

㻝㻚㻌㻱㼘㼘㼕㼟㻌㻺㻭㻘㻌㻳㼞㼛㼐㼑㼚㻌㻶㻘㻌㼅㼑㻌㼀㼆㻘㻌㻿㼠㼞㼍㼡㼓㼔㼑㼚㻌㻶㻘㻌㻸㼑㼚㼚㼛㼚㻌㻰㻶㻘㻌㻯㼕㼛㼏㼏㼕㻌㻿㻘㻌㻼㼞㼛㼥㼠㼏㼔㼑㼢㼍㻌㻹㻘㻌㻳㼑㼞㼙㼍㼚㻌㻶㻚㻌 㼀㼔㼑㻌㻮㼘㼛㼛㼙㻓㼟㻌㼟㼥㼚㼐㼞㼛㼙㼑㻌㼓㼑㼚㼑㻌㼜㼞㼛㼐㼡㼏㼠㻌㼕㼟㻌㼔㼛㼙㼛㼘㼛㼓㼛㼡㼟㻌㼠㼛㻌㻾㼑㼏㻽㻌㼔㼑㼘㼕㼏㼍㼟㼑㼟㻚㻌㻯㼑㼘㼘㻚㻌㻝㻥㻥㻡㻌㻺㼛㼢㻌 㻝㻣㻧㻤㻟㻔㻠㻕㻦㻢㻡㻡㻙㻢㻢㻚㻌

㻞㻚㻌㻯㼔㼍㼓㼍㼚㼠㼕㻌㻾㻿㻘㻌㻿㼏㼔㼛㼚㼎㼑㼞㼓㻌㻿㻘㻌㻳㼑㼞㼙㼍㼚㻌㻶㻚㻌㻭㻌㼙㼍㼚㼥㼒㼛㼘㼐㻌㼕㼚㼏㼞㼑㼍㼟㼑㻌㼕㼚㻌㼟㼕㼟㼠㼑㼞㻌㼏㼔㼞㼛㼙㼍㼠㼕㼐㻌㼑㼤㼏㼔㼍㼚㼓㼑㼟㻌㼕㼚㻌 㻮㼘㼛㼛㼙㻓㼟㻌㼟㼥㼚㼐㼞㼛㼙㼑㻌㼘㼥㼙㼜㼔㼛㼏㼥㼠㼑㼟㻚㻌㻼㼞㼛㼏㻌㻺㼍㼠㼘㻌㻭㼏㼍㼐㻌㻿㼏㼕㻌㼁㻌㻿㻌㻭㻚㻌㻝㻥㻣㻠㻌㻺㼛㼢㻧㻣㻝㻔㻝㻝㻕㻦㻠㻡㻜㻤㻙㻝㻞㻚㻌

㻟㻚㻌㻷㼍㼚㼑㼗㼛㻌㻴㻘㻌㻷㼛㼚㼐㼛㻌㻺㻚㻌㻯㼘㼕㼚㼕㼏㼍㼘㻌㼒㼑㼍㼠㼡㼞㼑㼟㻌㼛㼒㻌㻮㼘㼛㼛㼙㻌㼟㼥㼚㼐㼞㼛㼙㼑㻌㼍㼚㼐㻌㼒㼡㼚㼏㼠㼕㼛㼚㻌㼛㼒㻌㼠㼔㼑㻌㼏㼍㼡㼟㼍㼠㼕㼢㼑㻌㼓㼑㼚㼑㻘㻌 㻮㻸㻹㻌㼔㼑㼘㼕㼏㼍㼟㼑㻚㻌㻱㼤㼜㼑㼞㼠㻌㻾㼑㼢㻌㻹㼛㼘㻌㻰㼕㼍㼓㼚㻚㻌㻞㻜㻜㻠㻌㻹㼍㼥㻧㻠㻔㻟㻕㻦㻟㻥㻟㻙㻠㻜㻝㻚㻌

㻠㻚㻌㻭㼞㼛㼞㼍㻌㻴㻘㻌㻯㼔㼍㼏㼛㼚㻌㻭㻴㻘㻌㻯㼔㼛㼡㼐㼔㼍㼞㼥㻌㻿㻘㻌㻹㼏㻸㼑㼛㼐㻌㻹㻼㻘㻌㻹㼑㼟㼔㼗㼛㼢㻌㻸㻘㻌㻺㼛㼡㼞㼕㻌㻷㻘㻌㻵㼦㼍㼗㼛㼢㼕㼏㻌㻶㻚㻌㻮㼘㼛㼛㼙㻌 㼟㼥㼚㼐㼞㼛㼙㼑㻚㻌㻵㼚㼠㻌㻶㻌㻰㼑㼞㼙㼍㼠㼛㼘㻚㻌㻞㻜㻝㻠㻌㻶㼡㼘㻧㻡㻟㻔㻣㻕㻦㻣㻥㻤㻙㻤㻜㻞㻚㻌

㻡㻚㻌㔠Ꮚⱥ㞝㻚㻌㻮㼘㼛㼛㼙㻔䝤䝹䞊䝮㻕⑕ೃ⩌㻚㻌ู෉᪥ᮏ⮫ᗋ㻌 ච␿⑕ೃ⩌㻔➨㻞∧㻕㻵㻵㻵㻘㻌᪥ᮏ⮫ᗋ♫㻚㻌 㻞㻜㻝㻡㻦㻌㻞㻜㻜㻙㻞㻜㻞㻚㻌

㻮㼘㼛㼛㼙⑕ೃ⩌デ᩿䝣䝻䞊䝏䝱䞊 䝖 㻔᱌㻕 ⣚ᩬ 䠄 ከ䛟䛿 㢋㒊 䛻 ᑐ⛠ⓗ 䠅 䛛䜙 䜏䜙 䜜䜛ᆒ ᩚ䛾 䛸 䜜䛯 ᑠ᯶ 䛺 యᆺ ඲⑕ 䠄 ከ䛟䛿 ᢠయ ⏘⏕୙ ඲ ,J0 PJGO ௨ୗ 䠅 ᪤  ㇺ ⬟ప ୗ䠄 ᪩ ᮇ䛾 㛢⤒ 䚸 ୙ዷ 䠅

ጜጒᰁ Ⰽศ య⤌ ࡳ᥮࠼

%ORRP ⑕ೃ⩌␲䛔⑕౛ ஹ 㐍 ṇ ᖖ 㻮㻸㻹㑇ఏᏊ᳨ᰝ ☜ ᐃ デ ᩿

␗ᖖ࠶ ࡾ ␗ᖖ࡞ ࡋ ᬻ ᐃ デ ᩿ ᐃ ᮇ೺デ ࡟ࡼࡿ ᝏᛶ⭘ ⒆ࡢࢫ ࢡ࣮ࣜ ࢽࣥࢢ ⾑ ᾮ୍⯡ ᳨ᰝࠊ ⭘⒆࣐ ࣮࣮࢝ ⏬ ീ᳨ᰝ ࡞࡝

㚷ูデ᩿

%ORRP ⑕ೃ ⩌ ᬻ ᐃ ⑕౛ 㻮 㻸 㻹 䝍 䞁 䝟 䜽 ศ ᯒ 㻹 㻸 㻼 㻭 ἲ ௚ 䛾 ೃ ⿵ 㑇 ఏᏊ䛾 ᥈⣴

デ⒪࢞࢖ࢻࣛ࢖ࣥ

⬚⭢పᙧᡂ㸭ࢹ࢕࣭ࢪ࣮ࣙࢪ(DiGeorge)⑕ೃ⩌㸭22q11.2 Ḟኻ⑕ೃ⩌㸧

A. ⑌ᝈᴫせ

ࢹ࢕࣭ࢪ࣮ࣙࢪ⑕ೃ⩌㸦DiGeorge syndrome :DGS㸧ࡣࠊ1965ᖺ࡟DiGeorgeࡀሗ

࿌ࡋࡓ⬚⭢పᙧᡂ࡟ࡼࡿ᫆ឤᰁᛶࠊ๪⏥≧⭢పᙧᡂ࡟ࡼࡿపCa⾑⑕࡜ඛኳᛶᚰ⑌ᝈࢆ

క࠺⑕ೃ⩌࡛࠶ࡿ^1㸧ࠋ⬇ᙧᡂึᮇ࡟࠾ࡅࡿ➨࠾ࡼࡧ➨ဗ㢌ᄞࡢ␗ᖖᙧែⓎ⏕ࡀཎᅉ

࡛࠶ࡿࠋ1981ᖺ࡟DGS ࡜ᰁⰍయ22q11.2 㡿ᇦࡢᚤ⣽Ḟኻࡢ㛵㐃ࡀሗ࿌ࡉࢀࠊከࡃࡢ DGSᝈ⪅ࡣࠊᰁⰍయ22q11.2㡿ᇦ࡟Ḟኻࢆ᭷ࡍࡿ^2㸧ࠋḞᦆ㒊఩࡟ࡣ⣙30ࡢ㑇ఏᏊࢆྵ

ࡴࠋ㸦ᅗ㸯㸧

DGS ௨እࡢ⑕ೃ⩌㸦Velocardiofacial syndrome ࡸ Conotruncal Anomaly Facial syndrome㸧࡛ࡶᰁⰍయ22q11.2㡿ᇦࡢḞኻࡀ᫂ࡽ࠿࡜࡞ࡾࠊࡇࢀࡽࡣໟᣓⓗ࡟22q11.2 Ḟኻ⑕ೃ⩌࡜࿧ࡤࢀࡿࡼ࠺࡟࡞ࡗࡓࠋ

⑕≧࡟╔┠ࡋࡓ⑌ᝈ༢఩ࡀ DGS ࡛࠶ࡾࠊᰁⰍయ 22q11.2 㡿ᇦࡢḞኻ⑕௨እ࡟ࡶࠊ CDH7^{ኚ␗ࠊᰁⰍయ} 10㹮13-14 ࡞࡝ࡑࡢ௚ࡢᰁⰍయ㡿ᇦࡢ␗ᖖࠊẕయࡢࣅࢱ࣑ࣥ㸿ࡸ

࢔ࣝࢥ࣮ࣝࡢᦤྲྀ࡞࡝ࡢ⎔ቃせᅉࡀDGS ࡢཎᅉ࡜࡞ࡿࠋDGS ࡜ 22q11.2 Ḟኻ⑕ೃ⩌

⑌ᝈࡢ㛵ಀࢆ㸦ᅗ2㸧࡟♧ࡍࠋ

B. ␿Ꮫ

22q11.2Ḟኻ⑕ೃ⩌ࡣࠊฟ⏕4000㸫6000ே࡟1ே࡜ሗ࿌ࡉࢀ࡚࠾ࡾࠊᰁⰍయᚤ⣽Ḟ ᦆ⑕ೃ⩌ࡢ࡞࠿࡛ࡣࠊ᭱ࡶ㢖ᗘࡀ㧗࠸^3㸧ࠋࡉࡽ࡟ࠊ22q11.2Ḟኻ⑕ೃ⩌ࡣࠊከᵝ࡞⾲⌧

ᆺࢆ♧ࡋࠊ⮫ᗋ⑕≧ࡀ㍍ࡃデ᩿ࡉࢀ࡚࠸࡞࠸⑕౛ࡶከ࠸࡜᥎ᐃࡉࢀࡿࠋ

C. デ᩿ᇶ‽㸪デ᩿ࡢᡭᘬࡁ 㸯㸧⮫ᗋ⑕≧ࠊ㌟యᡤぢ

a. ๪⏥≧⭢పᙧᡂ࡟ࡼࡿపCa⾑⑕࡟ࡼࡿ⑕≧

b. ⬚⭢పᙧᡂ࡟ࡼࡿ᫆ឤᰁᛶ

c. ᚰὶฟ㊰ወᙧ ࣇ࢓࣮ࣟᅄᚩ⑕ࠊ෇㗹ື⬦⟶ᚰወᙧࠊ኱ື⬦ᘪ㞳᩿ࠊྑ኱ື

⬦ᘪࠊྑ㙐㦵ୗື⬦㉳ጞ␗ᖖ➼ࡢᚰወᙧ࡞࡝

d. ≉␗ⓗ㢦ㇺ ཱྀ⵹⿣ࠊప఩⪥௓ࠊᑠ⪥௓ࠊ▛⿣▷⦰ࢆక࠺║ゅ㝸㞳⑕ࠊ▷

࠸ே୰ࠊᑠࡉ࡞ཱྀࠊᑠ㢡⑕࡞࡝

e. ⢭⚄Ⓨ㐩㐜ࠊゝㄒⓎ㐩㐜

㸰㸧᳨ᰝᡤぢ

a. ప࢝ࣝࢩ࣒࢘⾑⑕ࠊ๪⏥≧⭢ᶵ⬟పୗ

b. T ⣽⬊ᩘࡣῶᑡ࠾ࡼࡧᶵ⬟పୗ

c. B ⣽⬊ᩘࡣṇᖖࠊච␿ࢢࣟࣈ್ࣜࣥࡣṇᖖ࠿ῶᑡ d. ⏬ീ᳨ᰝࡸᚰ࢝ࢸ࣮ࢸࣝ࡟ࡼࡿᚰወᙧࡢྠᐃ

e. ⬚㒊X⥺࡟ࡼࡿ⬚⭢㝜ᙳࡢḞᦆ

㸱㸧≉Ṧ᳨ᰝ

☜ ᐃ デ ᩿ ࡜ ࡋ ࡚ ࠊ ᚤ ⣽ ᰁ Ⰽ య Ḟ ኻ ⑕ ೃ ⩌ ࡜ ࡋ ࡚ ᰁ Ⰽ య 22q11.2 ࡢ ᚤ ⣽ Ḟ ኻ ࢆ fluorescence in situ hybridization (FISH) ࡸ array comparative genomic hybridization (aCGH) ࡟࡚ྠᐃࡍࡿࠋ≉࡟ TBX1 ^㑇ఏᏊ ࡢࣁࣉࣟ୙඲ࡀ㌟యⓗወᙧ ࡢฟ⌧࡟኱ࡁ࡞ᙺ๭ࢆᯝࡓࡍ࡜ࡉࢀࡿࠋᖖᰁⰍయඃᛶ㑇ఏᙧᘧ࠿ de novo ^{㑇ఏᙧᘧࢆ}

࡜ࡿࠋ

㏆ᖺࡢḟୡ௦ࢩ࣮ࢣࣥࢧ࣮ࡢⓎ㐩࡟ࡼࡾࠊච␿⬟ࡢపୗ࡟㛵㐃ࡍࡿ㑇ఏᏊኚ␗ࡸ

22q11.2Ḟኻ࡞࡝ࡢᰁⰍయ␗ᖖࢆ⥙⨶ⓗ࡟᳨ᰝࡍࡿࡇ࡜ࡀྍ⬟࡜࡞ࡗࡓ^4㸧ࠋ௒ᚋࠊ㠀඾

ᆺⓗ࡞⾲⌧ᆺࢆ♧ࡍሙྜ࡛ࡣࠊࡇࡢࡼ࠺࡞᳨ᰝἲࡀ୺ὶ࡟࡞ࡿ࡜⪃࠼ࡽࢀࡿࠋ

㸲㸧デ᩿ࡢ㐍ࡵ᪉

ୖグ⮫ᗋ⑕≧ࠊᐙ᪘Ṕࡢ᭷↓࠿ࡽᮏ⑌ᝈࡀ␲ࢃࢀࡿሙྜࡣࠊFISH ゎᯒࡸ aCGH ࡛ 22q11.2㡿ᇦࡢḞኻࢆ┤᥋ド᫂ࡍࡿࠋ22q11.2㡿ᇦࡢḞኻࡀㄆࡵࡽࢀ࡞࠸ሙྜࡣࠊᰁⰍ య10p13-14➼ࡑࡢ௚ࡢᰁⰍయḞኻࢆ᳨⣴ࡍࡿࠋච␿⬟ࡢホ౯࡜ࡋ࡚CD3㝧ᛶT ⣽⬊

ᩘࠊ࣐࢖ࢺࢪ࢙ࣥ࡟ᑐࡍࡿࣜࣥࣃ⌫ⱆ⌫໬཯ᛂࠊT-cell receptor excision circle㸦TREC㸧

࡟ࡼࡿT⣽⬊᪂⏕⬟ࢆホ౯ࡍࡿࠋ

Ḣ⡿࡛ࡣࠊTRECࢆ⏝࠸ࡓ㔜⑕」ྜච␿୙඲⑕࡟ᑐࡍࡿ᪂⏕ඣ࣐ࢫࢫࢡ࣮ࣜࢽࣥࢢࡀ 㛤ጞࡉࢀࠊT⣽⬊᪂⏕⬟ࡢపୗࢆ♧ࡍ᪂⏕ඣࡢ୍㒊ࡀDGS࡜デ᩿ࡉࢀ࡚࠸ࡿ^5㸧ࠋ௒ᚋࠊ

᪥ᮏ࡛ࡶࠊࡇࡢ࣐ࢫࢫࢡ࣮ࣜࢽࣥࢢࡀ㛤ጞࡉࢀࢀࡤࠊDGS ࡣ᪂⏕ඣ࣐ࢫࢫࢡ࣮ࣜࢽࣥ

ࢢ࡛ぢࡘ࠿ࡿ⑌ᝈ࡜࡞ࡿྍ⬟ᛶࡀ࠶ࡿࠋ

㸳㸧㚷ูデ᩿

࠸ࡃࡘ࠿ࡢ㑇ఏᏊኚ␗ࡸദወᙧᛶ≀㉁ࡢᙳ㡪࡟ࡼࡾࠊ22q11.2Ḟኻ⑕ೃ⩌࡜ྠࡌࡼ࠺

࡞⾲⌧ᆺࢆ♧ࡍࡇ࡜ࡀ▱ࡽࢀ࡚࠸ࡿࠋCHARGE㸦ccoloboma of the eye, hheart anomalies, choanal atresia, rretardation, ggenital and eear anomalies㸧⑕ೃ⩌ࡣࠊඛኳᛶᚰ⑌ᝈࠊ

ཱྀ⵹⿣ࠊ㞴⫈࡞࡝ࡢ22q11.2Ḟኻ⑕ೃ⩌࡜ྠᵝࡢ⑕≧ࢆ♧ࡍࡀࠊࢥ࣮࣐ࣟ࣎ࠊᚋ㰯⭍ࡢ 㛢ሰࠊ⏕Ṫჾወᙧ➼ࡢDGS࡛ࡣぢࡽࢀ࡞࠸⑕≧ࢆ᭷ࡍࡿࠋCHARGE⑕ೃ⩌ࡢከࡃ࡛ࠊ CHD7^{ࡢኚ␗ࡀㄆࡵࡽࢀࡿࠋ}

D. ྜే⑕

ᛶ㞴⫈ࡢྜేࡀㄆࡵࡽࢀࡿࠋᦤ㣗࣭ᄟୗࡢၥ㢟࠿ࡽㄗᄟᛶ⫵⅖ࢆ⧞ࡾ㏉ࡍࡇ࡜ࡀ࠶ࡿࠋ E

E. 㔜⑕ᗘศ㢮

DGS ࡢ࠺ࡕࠊ0.5㹼1㸣࡛᏶඲࡟⬚⭢⤌⧊ࡀḞᦆࡋ࡚࠾ࡾࠊ᏶඲ᆺ DiGeorge ⑕ೃ

⩌㸦complete DiGeorge syndrome :cDGS㸧࡜࿧ࡤࢀࠊ㔜⠜࡞⣽⬊ᛶච␿୙඲⑕ࢆ࿊ࡍ

ࡿࠋࡉࡽ࡟20%ࡣࠊ୙᏶඲ᆺDiGeorge⑕ೃ⩌㸦partial DiGeorge syndrome :pDGS㸧

࡜࿧ࡤࢀࠊ୰➼ᗘ௨ୖࡢ⣽⬊ᛶච␿ᶵ⬟ࡢపୗࢆྜేࡍࡿࠋcDGS࡜pDGSࡢデ᩿ᇶ‽

ࢆ㸦⾲㸯㸧࡟♧ࡍࠋ

F. ἞⒪

⑕≧ࡀከᒱ࡟ࢃࡓࡿࡓࡵࠊໟᣓⓗ࡞⟶⌮ࡀᚲせ࡜࡞ࡿࠋච␿⬟࡟㛵ࡋ࡚ࠊ᭱㔜⑕ࡢ cDGS ࡀ␲ࢃࢀࡿሙྜ࡛ࡣᝈ⪅ࢆ㝸㞳ࡋࠊ࣐࢞ࣥࢢࣟࣈࣜࣥ㟼ὀࡸ Pneumocystis jirovecii⫵⅖ࡸ┿⳦ឤᰁ⑕ࡢண㜵ࡢࡓࡵࡢSTྜ๣ࡸᢠ┿⳦⸆ࡢண㜵ෆ᭹ࢆ⾜࠺ࠋ㍺⾑

࡟ࡼࡿGVHDⓎ⑕ࡢࣜࢫࢡࡸCMVឤᰁࡢࣜࢫࢡࡀ࠶ࡿࡓࡵࠊᨺᑕ⥺ᮍ↷ᑕ⾑࠶ࡿ࠸

ࡣCMV㝧ᛶ⾑ᾮ〇๣ࡢ౑⏝ࡣ㑊ࡅࡿࠋⴭ᫂࡞ᮎᲈ⾑T⣽⬊ῶᑡࡀ᫂ࡽ࠿࡞ሙྜࠊT⣽

⬊ᶵ⬟㞀ᐖࡀ࠶ࡿሙྜࠊᶵ⬟ᛶᢠయࡢ⏘⏕ࡀ࡞࠸ሙྜࡣ⏕࢘࢖ࣝࢫ࣡ࢡࢳࣥࡢ᥋✀ࢆ᥍

࠼ࡿࠋ

᰿἞⾡࡜ࡋ࡚ࡣࠊ⬚⭢⛣᳜ࡀ᭱ࡶ᰿ᮏⓗ࡞἞⒪ἲ࡛࠶ࡿ^6㸧ࠋᚰ⮚ᡭ⾡ࡢ㝿࡟ᚓࡽࢀࡓ

⬚⭢⤌⧊ࢆᇵ㣴ࡋࠊᇵ㣴⬚⭢⤌⧊ࢆᝈ⪅ࡢ኱⭣ᅄ㢌➽࡟⛣᳜ࡋ࡚ T ⣽⬊ᶵ⬟ࢆᵓ⠏ࡍ

ࡿࠋࡋ࠿ࡋ࡞ࡀࡽ⬚⭢⛣᳜ࡣࠊḢ⡿ࡢࡈࡃ㝈ࡽࢀࡓ᪋タ࡛ࡢࡳ᪋⾜ྍ⬟࡛࠶ࡿࠋ

⬚⭢⛣᳜௨እࡢ᰿἞⾡࡜ࡋ࡚ࠊ㐀⾑⣽⬊⛣᳜ࡀ᪋⾜ࡉࢀࡿࠋࢻࢼ࣮⏤᮶ࡢ⬚⭢࡛ᩍ⫱

ࢆཷࡅࡓᮎᲈ⾑ࣜࣥࣃ⌫ࡀࠊᝈ⪅యෆ࡛ቑṪࡍࡿࡇ࡜࡟ࡼࡾච␿⬟ࡢᵓ⠏ࡀᚓࡽࢀࡿࡀࠊ T⣽⬊ཷᐜయࣞࣃࢺ࢔ࡢከᵝᛶࡣไ㝈ࡉࢀࡿ^7㸧ࠋᚑ᮶ࠊ⛣᳜ࢯ࣮ࢫ࡜ࡋ࡚ࠊ㦵㧊ࡀ౑⏝

ࡉࢀ࡚࠸ࡓࡀࠊ㏆ᖺࠊ⮖ᖏ⾑࡛ࡶⰋዲ࡞ච␿⬟ࡢ෌ᵓᡂࡀ♧ࡉࢀࡓ^8㸧ࠋ

௚ࡢྜే⑕࡟㛵ࡋ࡚ࠊᚰወᙧࡢྜే౛࡛ࡣࠊ⏕ᚋ㛫ࡶ࡞ࡃᡭ⾡ࡀᚲせ࡜࡞ࡿࡇ࡜ࡀ࠶

ࡾࠊ⏕࿨ணᚋࡣྜేࡍࡿᚰወᙧࡢ㔜⑕ᚋ࡟ᕥྑࡉࢀࡿࠋప࢝ࣝࢩ࣒࢘⾑⑕࡟ᑐࡋ࡚ࡣࠊ

๪⏥≧⭢ᶵ⬟పୗ⑕࡟‽ࡌ࡚἞⒪ࢆ⾜࠺ࠋ඲㌟≧ែࡢᏳᐃᚋࠊឤᰁ⑕࡟㓄៖ࡋ࡞ࡀࡽࠊ

Ⓨ㐩㞀ᐖ࡟ᑐࡋࠊ⒪⫱ࢆཷࡅࡿࡇ࡜ࡀ኱ษ࡛࠶ࡿࠋ㛗ᮇⓗ࡟ࡣࠊ⮬ᕫච␿⑌ᝈࡸ⢭⚄⑌

ᝈ࡞࡝ࡀぢࡽࢀࡿࡇ࡜ࡀ࠶ࡾࠊከ᪉㠃࠿ࡽࡢ࢔ࣉ࣮ࣟࢳࡀᚲせ࡛࠶ࡿࠋ

ᖺ㱋ูࡢホ౯㡯┠࡟㛵ࡋ࡚ࠊࠕ22q11.2Ḟኻ⑕ೃ⩌ᅜ㝿ࢥࣥࢯ࣮ࢩ࢔࣒ࠖࡀ2011ᖺ࡟

Ⓨ⾲ࡋࡓ⟶⌮࢞࢖ࢻࣛ࢖ࣥ࡟グ㍕ࡉࢀ࡚࠸ࡿ^9㸧ࠋ

G. ணᚋࠊᡂேᮇࡢㄢ㢟

DGS ᝈ⪅ࡢணᚋࡣᚰወᙧ࡜ච␿⬟ࡢ⛬ᗘ࡟౫ᏑࡍࡿࠋᗂᑡᮇࡢṚᅉࡣࠊᚰወᙧࡀ᭱

ከ

࡛࠶ࡾࠊ᪥࿴ぢឤᰁ⑕ࡀࡑࡢḟ࡟ከ࠸ࠋᚤᑠ࡞⬚⭢⤌⧊ࡀṧᏑࡋ࡚࠸ࡿሙྜࡣࠊᡂ㛗࡟

క࠸T⣽⬊ᩘࡀ⮬↛࡟ᅇ᚟ࡍࡿࠋ㐀⾑⣽⬊⛣᳜ࢆཷࡅࠊⰋዲ࡞ච␿⬟ࡢᵓ⠏ࡀᚓࡽࢀࡓ ᝈ⪅ࡣࠊ㛗ᮇ㛫࡟ࢃࡓࡾឤᰁ⑕࡟⨯ᝈࡍࡿࡇ࡜ࡀᑡ࡞࠸ࠋ

22q11.2Ḟኻ⑕ೃ⩌࡛ࡣࠊฟ⏕᫬࡟ච␿⬟ࡢ␗ᖖࡀㄆࡵࡽࢀ࡞ࡃ࡚ࡶࠊᛮ᫓ᮇ௨㝆࡟

ప࣐࢞ࣥࢢࣟࣈࣜࣥ⾑⑕➼ࡢᾮᛶච␿୙඲ࢆⓎ⑕ࡍࡿࡇ࡜ࡀ࠶ࡿࠋ

H

H. デ⒪ୖὀពࡍ࡭ࡁⅬࠊ

ṇᖖ࡞ච␿ࡢⓎ㐩ࡀ⾜ࢃࢀ࡞࠸ࡇ࡜࡟ࡼࡾ⮬ᕫච␿⑌ᝈࡢ㢖ᗘࡀቑຍࡍࡿࠋⱝᖺᛶ

≉Ⓨᛶ㛵⠇⅖(JIA)ࡸ⮬ᕫච␿ᛶ⾑⌫ῶᑡ⑕ࠊ⮬ᕫච␿ᛶ⏥≧⭢⑌ᝈࡀከ࠸ࠋ

ᅗ㸯 22␒ᰁⰍయୖࡢḞᦆ㒊఩࡜㑇ఏᏊ

ᅗ2 ⑌ᝈᴫᛕ

DiGeorge syndromeࡢከࡃࡣ22q11.2Ḟኻࢆక࠺ࠋ22q11.2Ḟኻࢆకࢃ࡞࠸DiGeorge syndrome࡛ࡣࠊCHD7^{ኚ␗ࡸᰁⰍయ}10p13-14➼ࡑࡢ௚ࡢᰁⰍయḞኻࡀཎᅉ࡜࡞ࡿࠋ

13 12 11䠉2 11䠉1 11䠉1 11䠉2 12䠉1 12䠉2 12䠉3 13䠉1 13䠉2 13䠉31 13䠉32 13䠉33

㸱㹋㹠

㑇ఏᏊ

䠠䠣䠟䠮䠒 䠠䠣䠟䠮䠎 䠠䠣䠟䠮䠍䠐 䠯䠨䠟䠎䠑䠝䠍 䠤䠥䠮䠝 䠱䠢䠠䠍䠨 䠟䠨䠠䠪䠑 䠣䠬䠍䠞䠞 䠣䠪䠞䠍䠨 䠟䠫䠩䠰 䠰䠝䠪䠣䠫䠎 䠰䠮䠩䠰䠎䠝 䠶䠠䠤䠤䠟䠔 䠶䠪䠢䠓䠐 䠯䠡䠮䠬䠥䠪䠠䠍 䠟䠮䠧䠨

䠬䠮䠫䠠䠤 䠰䠯䠯䠧䠍䠝 䠣䠯䠟䠎 䠟䠰䠟䠨䠍 䠩䠮䠬䠨䠐䠌 䠟䠠䠟䠐䠑 䠯䠡䠬䠰䠑 䠰䠞䠴䠍 䠰䠴䠪䠮䠠䠎 䠝䠮䠲䠟䠢 䠠䠣䠟䠮䠔 䠮䠝䠪䠞䠬䠍 䠮䠰䠪䠐䠮 䠯䠟䠝䠮䠢䠎 䠯䠪䠝䠬䠎䠕 䠨䠶䠰䠮䠍

22q11.2 Ḟኻ

⑕ೃ⩌ DiGeorge

syndrome

CHD7

௚䛾㡿ᇦ䛾ᰁⰍయ␗ᖖ 10p13-14

18q21.33 4q21.3-q25

⾲㸯 ᏶඲ᆺ࠾ࡼࡧ୙᏶඲ᆺDiGeorge⑕ೃ⩌ࡢデ᩿ᇶ‽

ศ㢮 ༊ศ

୙᏶඲ᆺDiGeorge⑕ೃ⩌ Definitive 3ṓᮍ‶࡛CD3㝧ᛶT⣽⬊ᩘࡀ500/ȣLᮍ‶࡜࡞

ࡾࠊᰁⰍయ 22q11.2 㡿ᇦࡢḞᦆ࡜㛵㐃ࡍࡿ෇㗹ື

⬦ᖿ㒊ࡢᚰወᙧࡲࡓࡣపCa⾑⑕ࢆㄆࡵࡿࠋ Probable 3ṓᮍ‶࡛CD3㝧ᛶT⣽⬊ᩘࡀ1500/ȣLᮍ‶࡜

࡞ࡾࠊᰁⰍయ22q11.2ࡢḞᦆࢆㄆࡵࡿࠋ

Possible 3ṓᮍ‶࡛CD3㝧ᛶT⣽⬊ᩘࡀ1500/ȣLᮍ‶࡜

࡞ࡾࠊඛኳᛶᚰ⑌ᝈࡶࡋࡃࡣపCa⾑⑕ࡶࡋࡃࡣ㢦 ㇺ/ཱྀ⵹ࡢወᙧࢆㄆࡵࡿࠋ

᏶඲ᆺDiGeorge⑕ೃ⩌ Definitive CD3㝧ᛶT⣽⬊ᩘࡀ50/ȣLᮍ‶࠿ࡘ⬚⭢↓ᙧᡂࠊ పCa⾑⑕ࠊඛኳᛶᚰ⑌ᝈࢆㄆࡵࡿࠋ

ᩥ⊩

1 DiGeorge A M. Discussion on a new concept of the cellular basis of immunology.

J Pediatr. 1965; 67::907.

2 de la Chapelle A, Herva R, Koivisto M, et al. A deletion in chromosome 22 can cause DiGeorge syndrome. Hum Genet. 1981; 57:253–256.

3 Wilson D, Burns J, Scambler P, et al. DiGeorge syndrome: part of CATCH 22. J Med Genet 1993; 30:852-6.

4 Kojima D, Wang X, Muramatsu H, et al. Application of extensively targeted next- generation sequencing for the diagnosis of primary immunodeficiencies. J Allergy Clin Immunol. 2016; 138:303-305.

5 Kwan A, Abraham RS, Currier R, et al. Newborn screening for severe combined immunodeficiency in 11 screening programs in the United States. JAMA. 2014;

312:729-38.

6 Markert ML, Devlin BH, Alexieff MJ, et al. Review of 54 patients with complete DiGeorge anomaly enrolled in protocols for thymus transplantation: outcome of 44 consecutive transplants. Blood 2007; 109:4539-47.

7 Land MH, Garcia-Lloret MI, Borzy MS, et al. Long-term results of bone marrow transplantation in complete DiGeorge syndrome. J Allergy Clin Immunol 2007;

120:908-15.

8 Kojima D, Muramatsu H, Okuno Y, et al. Successful T-cell reconstitution after unrelated cord blood transplantation in a patient with complete DiGeorge syndrome.

J Allergy Clin Immunol 2016; Epub ahead of print.

9 Bassett AS, McDonald-McGinn DM, Devriendt K, et al. Practical guidelines for managing patients with 22q11.2 deletion syndrome. J Pediatr 2011; 159:332-9.

デ⒪࢞࢖ࢻࣛ࢖ࣥ

ඛኳᛶゅ໬୙඲⑕

A. ⑌ᝈᴫせ

ඛኳᛶゅ໬୙඲⑕㸦DC; Dyskeratosis congenita㸧ࡣࠊࢸ࣓ࣟ࢔㛗⥔ᣢ࡟㛵୚ࡍࡿ㑇 ఏᏊ⩌ࡢኚ␗࡟ࡼࡾⓎ⑕ࡍࡿඛኳᛶ㐀⾑୙඲⑕ೃ⩌ࡢ୍ࡘ࡛࠶ࡿࠋྂ඾ⓗ࡞⓶⭵࣭⢓⭷

࡟࠾ࡅࡿ୕ᚩࡣࠊ∎ࡢᙧᡂ␗ᖖ࣭࣮ࣞࢫ≧ࡢ⓶⭵Ⰽ⣲ỿ╔ཱྀ࣭⭍ෆⓑᯈ⑕࡛࠶ࡿࡀࠊࡇ

ࢀࡽࡢ㌟య␗ᖖࡀࡑࢁࢃ࡞࠸୙඲ᆺඛኳᛶゅ໬୙඲⑕ࡢᏑᅾࡀ▱ࡽࢀ࡚࠸ࡿࠋ୍᪉ࠊᑠ

⬻పᙧᡂ࣭ච␿୙඲࣭㐍⾜ᛶࡢ㦵㧊୙඲࣭ᏊᐑෆⓎ⫱㐜ᘏ࡞࡝ࡢ≉ᚩࢆ᭷ࡍࡿ㔜⑕౛ࡣ Hoyeraal-Hreidarsson syndrome㸦HHS㸧࡜࿧ࡤࢀࡿ¹ࠋ

ࢸ࣓ࣟ࢔࡜ࡣࠊ⬨᳝ື≀ࡢᰁⰍయࡢ୧ᮎ➃࡟Ꮡᅾࡍࡿ 6 ሷᇶ㸦TTAGGG㸧ࡢ⧞ࡾ㏉

ࡋ㓄ิࡢࡇ࡜࡛࠶ࡿࠋࢸ࣓࣮ࣟࣛࢮ࡟ࡼࡗ࡚ࢸ࣓ࣟ࢔㛗ࡢ⥔ᣢࡀ࡞ࡉࢀ࡞ࡅࢀࡤࠊᰁⰍ యࡢᮎ➃ࡣ⣽⬊ࡢศ⿣ࡈ࡜࡟⾜ࢃࢀࡿDNAࡢ」〇ࡢ㝿࡟ᚎࠎ࡟๐ࡽࢀ࡚ࡋࡲ࠸ࠊ㔜せ

࡞㑇ఏ᝟ሗࡀኻࢃࢀ࡚ࡋࡲ࠺ࠋࡓࡔࡇࡢᶵ⬟ࡣṇᖖ⣽⬊࡟࠾࠸࡚ࡶ᏶඲࡛ࡣ࡞ࡃࠊ

50-150 ሷᇶᑐࡀ⣽⬊ศ⿣ẖ࡟ኻࢃࢀ࡚࠸ࡿࠋࢸ࣓ࣟ࢔㛗ࡢ▷⦰ࡋࡓᰁⰍయࢆࡶࡘ⣽⬊

ࡣࠊᰁⰍయᮎ➃ࡀDNA ࡢ஧ᮏ㙐ษ᩿㒊఩࡜ࡋ࡚ㄆ㆑ࡉࢀࠊDNAᦆയ཯ᛂ࠾ࡼࡧp53 ࡢάᛶ໬ࡀច㉳ࡉࢀࠊ⣽⬊ࡢ⪁໬࣭࢔࣏ࢺ࣮ࢩࢫ࡟⮳ࡿࠋࡑࡢࡓࡵࠊ⣽⬊ቑṪࡀ┒ࢇ࡞

⓶⭵ࠊ㦵㧊࡞࡝ࡢ⤌⧊ࡀ㧗⋡࡟౵ࡉࢀࡿࡶࡢ࡜⪃࠼ࡽࢀ࡚࠸ࡿࠋᅗ㸯࡟♧ࡍࡼ࠺࡟ࠊࢸ

࣓࣮ࣟࣛࢮ」ྜయࠊshelterin ࡜࠸࠺2 ࡘࡢ㔜せ࡞ࢥ࣏࣮ࣥࢿࣥࢺࡀࠊṇᖖ࡞ࢸ࣓ࣟ࢔

㛗ࡢ⥔ᣢࡢᙺ๭ࢆᢸࡗ࡚࠸ࡿࠋࢸ࣓࣮ࣟࣛࢮ」ྜయࡣ RNA ࢥ࣏࣮ࣥࢿࣥࢺ࡛࠶ࡿ

TERCࢆ㗪ᆺ࡜ࡋࠊTERTࡢ㏫㌿෗㓝⣲άᛶ࡟ࡼࡾࢸ࣓ࣟ࢔ࢆఙ㛗ࡍࡿࠋShelterinࡣ

≀⌮ⓗ࡟ࢸ࣓ࣟ࢔ࡢᏳᐃᛶ࡟㛵୚ࡋ࡚࠸ࡿ࡜⪃࠼ࡽࢀ࡚࠸ࡿࠋࢸ࣓࣮ࣟࣛࢮ」ྜయ㛵㐃 㑇ఏᏊࡢ࠺ࡕࠊDKC1,TERT,TERC,NOP10,NHP2 ^ࡀࠊshelterin ࡢࢥ࣏࣮ࣥࢿࣥࢺ࡛

࠶ࡿTIN2࡜TPP1ࢆࡑࢀࡒࢀࢥ࣮ࢻࡍࡿTINF2,ACDࡀཎᅉ㑇ఏᏊ࡜ࡋ࡚ྠᐃࡉࢀ࡚

࠸ࡿࠋWRAP53 ^{ࡣࢸ࣓࣮ࣟࣛࢮࡢ᰾ෆ} Cajalయ࡬ࡢᒁᅾࢆไᚚࡋ࡚࠾ࡾࠊ㑇ఏᏊኚ␗

࡟ࡼࡾࢸ࣓࣮ࣟࣛࢮᒁᅾࡀ㞀ᐖࡉࢀࡿࡇ࡜࡛ࢸ࣓ࣟ࢔㛗⥔ᣢࡀ㞀ᐖࡉࢀࡿࠋࡲࡓࠊ2013 ᖺ࡟ࡣHHSᝈ⪅ࡢ඲࢚ࢡࢯࣥゎᯒ࡟ࡼࡾࠊDNA2ᮏ㙐ࢆ࡯࡝ࡃDNA࣮࣊ࣜ࢝ࢮࢆࢥ

࣮ࢻࡍࡿRTEL1ࡀཎᅉ㑇ఏᏊ࡜ྠᐃࡉࢀࡓࠋCST」ྜయ㸦CTC1,TEN1,STN1㸧ࡣࢸ

࣓ࣟ࢔࡜┦஫స⏝ࡋ࡚ࢸ࣓ࣟ࢔ಖㆤ࡜ࢸ࣓ࣟ࢔DNA」〇ไᚚ࡟㛵୚ࡍࡿࠋCST」ྜయ ࡢࢥ࣏࣮ࣥࢿࣥࢺࢆࢥ࣮ࢻࡍࡿCTC1^ࡀDCࡢཎᅉ㑇ఏᏊ࡜ࡋ࡚ྠᐃࡉࢀ࡚࠸ࡿࠋ2015 ᖺ࡟㔜⑕DCᝈ⪅ࡢ඲࢚ࢡࢯࣥゎᯒ࡟ࡼࡾࠊmRNAࡢᏳᐃᛶࢆไᚚࡍࡿ࣏ࣜA≉␗ⓗ

ࣜ࣎ࢾࢡࣞ࢔࣮ࢮࢆࢥ࣮ࢻࡍࡿ PARN ࡢ㑇ఏᏊኚ␗ࡀྠᐃࡉࢀࡓࠋࡇࡢᝈ⪅࡛ࡣ TERC,DKC1,RTEL1࡜࠸ࡗࡓࢸ࣓ࣟ࢔㛗⥔ᣢ࡟㔜せ࡞㑇ఏᏊࡢ mRNAࣞ࣋ࣝࡀపୗ

ࡋ࡚࠸ࡿࡇ࡜ࡀ♧ࡉࢀࠊPARN^㑇ఏᏊࡶDCࡢཎᅉ㑇ఏᏊ࡜ࡉࢀࡓࠋ௨ୖࡢ11㑇ఏᏊ

ACD^ࠊPARN^{㸧ࡀࡇࢀࡲ࡛࡟}DCࡢཎᅉ㑇ఏᏊ࡜ࡋ࡚ྠᐃࡉࢀ࡚࠸ࡿࠋ

B B. ␿Ꮫ

ᡃࡀᅜ࡟࠾࠸࡚ࡢṇ☜࡞⑕౛ᩘࡢ⤫ィࡣ࡞࠸ࡀࠊᾏእࡢሗ࿌࠿ࡽ᥎ᐃࡍࡿ࡜ 100 ୓

ே࡟㸯ே࡜ࡉࢀࡿ²ࠋ

C. デ᩿ᇶ‽ࠊデ᩿ࡢᡭᘬࡁ

㸯㸧⮫ᗋ⑕≧ࠊ㌟యᡤぢࠊ᳨ᰝᡤぢ

DCࡢ⮫ᗋデ᩿ࡣࠊ⓶⭵࣭⢓⭷࡟࠾ࡅࡿ୕ᚩ㸦∎ࡢᙧᡂ␗ᖖ࣭࣮ࣞࢫ≧ࡢ⓶⭵Ⰽ⣲ỿ

╔ཱྀ࣭⭍ෆⓑᯈ⑕㸧࡜㦵㧊୙඲⑕ࡢホ౯࡟ࡼࡿࡢࡀᇶᮏ࡛࠶ࡿࡀࠊࡇࡢ࡯࠿࡟ࡶ⢭⚄Ⓨ

㐩㐜ᘏ࣭⫵⥺⥔⑕࣭㣗㐨⊃✽࣭ⱝᖺᛶⓑ㧥࣭ᝏᛶ⭘⒆ࡢྜే࡞࡝ࠊከ⮚ჾ࡟ࢃࡓࡿ⑕≧

ࡀࡳࡽࢀࡿྍ⬟ᛶࡀ࠶ࡿࠋ⾲㸯࡟ࠊDCࡢデ᩿ᇶ‽ࢆ♧ࡍࠋ

㸰㸧≉Ṧ᳨ᰝࠊデ᩿ࡢ㐍ࡵ᪉

∎ࡢᙧᡂ␗ᖖ࣭࣮ࣞࢫ≧ࡢ⓶⭵Ⰽ⣲ỿ╔ཱྀ࣭⭍ෆⓑᯈ⑕࡞࡝ࡢ≉ᚩⓗ࡞㌟యⓗ␗ᖖࠊ 㦵㧊୙඲ࠊᐙ᪘Ṕ࡞࡝࠿ࡽDCࡀ␲ࢃࢀࡿሙྜ࡟ࡣࠊᮎᲈ⾑ࢆ⏝࠸࡚ flow-FISHࡲࡓ ࡣࢧࢨࣥࣈࣟࢵࢸ࢕ࣥࢢࢆ⏝࠸ࡓ⾑⌫ࢸ࣓ࣟ࢔㛗 ᐃࢆ⾜࠺ࠋࡋ࠿ࡋࠊᐇ㝿࡟ࡣ⮫ᗋ⑕

≧ࡀᥞࢃ࡞࠸୙඲ᆺࡢᏑᅾࡀ▱ࡽࢀ࡚࠾ࡾࠊ㌟యⓗ≉ᚩࢆ᭷ࡉ࡞࠸෌⏕୙Ⰻᛶ㈋⾑ᝈ⪅

ࡢ୰࡟ࡶᮏ⑕ࡀྵࡲࢀࡿࡇ࡜ࡀ᫂ࡽ࠿࡟࡞ࡗ࡚ࡁ࡚࠸ࡿࡓࡵࠊ෌⏕୙Ⰻᛶ㈋⾑ᝈ⪅࡟ᑐ ࡋ࡚ࡣࠊデ᩿᫬࡟ࢸ࣓ࣟ࢔㛗᳨ᰝࢆ⾜࠺ࡇ࡜ࡀᮃࡲࡋ࠸ࠋ

ࢸ࣓ࣟ࢔㛗 ᐃἲ࡟ࡣࢧࢨࣥࣈࣟࢵࢸ࢕ࣥࢢἲ࣭ᐃ㔞PCRἲ࣭Flow-FISHἲ࡞࡝ࡀ

࠶ࡿࡀࠊࡇࡇ࡛ࡣྡྂᒇ኱Ꮫᑠඣ⛉࡛⾜ࡗ࡚࠸ࡿ Flow-FISH ἲࢆ⤂௓ࡍࡿ ³ࠋࢸ࣓ࣟ

࢔㛗ࡣຍ㱋࡜࡜ࡶ࡟▷⦰ࡍࡿࡓࡵࠊᮎᲈ⾑ࣜࣥࣃ⌫ࡢࢸ࣓ࣟ࢔㛗ࢆPNA kit ࢆ⏝࠸ࡓ

flow-FISH ἲ࡟࡚ ᐃࡋࡓᚋ࡟ᖺ㱋ࢆ࣐ࢵࢳࡉࡏࡓ೺ᖖࢥࣥࢺ࣮ࣟࣝ࠿ࡽᶆ‽೫ᕪ

㸦SD㸧ࢆ⟬ฟࡋࠊᝈ⪅ࡢ┦ᑐࢸ࣓ࣟ࢔㛗ࢆホ౯ࡋ࡚࠸ࡿࠋᅗ2࡟ࠊࢸ࣓ࣟ࢔㛗▷⦰㸦-2.9 SD㸧ࢆㄆࡵࡓ 2 ṓඣࡢゎᯒ⤖ᯝࢆ♧ࡍࠋࡇࡢ⑕౛ࡢࡼ࠺࡟ࠊ᫂ࡽ࠿࡞ࢸ࣓ࣟ࢔㛗▷⦰

ࡀㄆࡵࡽࢀࡿ⑕౛࡛ࡣࠊDCࡢྜేࢆ⪃៖ࡋࠊ㑇ఏᏊゎᯒ࡟ࡼࡿ☜ᐃデ᩿ࢆ⾜࠺ࡇ࡜ࡀ ᮃࡲࡋ࠸ࠋ

☜ᐃデ᩿ࡣࠊ㑇ఏᏊデ᩿ࡀ᭷⏝࡛࠶ࡿࡀࠊୖ㏙ࡢࡼ࠺࡟ࡇࢀࡲ࡛ࡢ◊✲࡛11 㑇ఏᏊ ࡀཎᅉ㑇ఏᏊ࡜ࡋ࡚ྠᐃࡉࢀ࡚࠾ࡾࠊࡲࡓࢸ࣓ࣟ࢔㛗ࡀ▷⦰ࡋ࡚࠸ࡿࢩࣗࣂࢵࣁ࣐࣭ࣥ

ࢲ࢖࢔ࣔࣥࢻ⑕ೃ⩌ࡢᏑᅾࡀሗ࿌ࡉࢀ࡚࠾ࡾ⁴ࠊࢸ࣓ࣟ࢔㛗▷⦰౛࡛ࡣSBDS^㑇ఏᏊࡢ ゎᯒࡶ⾜࠺ᚲせࡀ࠶ࡿ࡜⪃࠼ࡽࢀࡿࠋゎᯒࡍ࡭ࡁ㑇ఏᏊᩘࡢቑຍ࡜࡜ࡶ࡟ࠊᚑ᮶ࡢࢧࣥ

࣮࢞ἲ࡟ࡼࡿ㑇ఏᏊゎᯒࡣデ᩿࡟ᚲせ࡞᫬㛫࡜ປຊࡢ୧㠃࠿ࡽ㝈⏺ࢆ㏄࠼࡚࠸ࡿࡇ࡜

࠿ࡽࠊḟୡ௦ࢩ࣮ࢡ࢚ࣥࢧ࣮ࢆ⏝࠸ࡓ⥙⨶ⓗ㑇ఏᏊゎᯒࡀᗈࡃ⮫ᗋ࡛฼⏝ࡉࢀࡿࡇ࡜ࡀ ᮇᚅࡉࢀࡿࠋ୍᪉ࠊ⌧ᅾ࡛ࡶ࠾ࡼࡑ༙ᩘࡢ⑕౛࡛ࡣཎᅉ㑇ఏᏊࡀ୙࡛᫂࠶ࡿࡓࡵࠊ᪤▱

ࡢ㑇ఏᏊኚ␗ࡀྠᐃࡉࢀ࡞ࡃ࡚ࡶDCࡢデ᩿ࢆྰᐃࡍࡿࡇ࡜ࡣ࡛ࡁ࡞࠸ࠋ ᅗ3࡟デ᩿ࡢࣇ࣮ࣟࢳ࣮ࣕࢺࢆ♧ࡍࠋ

㸱㸧㚷ูデ᩿

㚷 ู デ ᩿ ࡣ ࠊ ㌟ య ⓗ ␗ ᖖ ࢆ క ࠺ 㦵 㧊 ୙ ඲ ⑕ ࡜ ࡋ ࡚ ࠊFanconi ㈋ ⾑ ࠊ Schwachman-Diamond⑕ೃ⩌ࠊඛኳᛶ↓ᕧ᰾ⱆ⌫ᛶ⾑ᑠᯈῶᑡ⑕ࠊPearson⑕ೃ⩌࡞

࡝ࡢ⑌ᝈࢆ㚷ูࡍࡿᚲせࡀ࠶ࡿࠋࡑࢀࡒࢀ≉ᚩⓗ࡞⮫ᗋീࡀ࠶ࡿࡢ࡛ࡲࡎ⮫ᗋീ࠿ࡽ㚷

ูࡋ࡚࠸ࡃࡀࠊḟୡ௦ࢩ࣮ࢡ࢚ࣥࢧ࣮࡟ࡼࡿඛኳᛶ㦵㧊୙඲⑕ࢆᑐ㇟࡟ࡋࡓ⥙⨶ⓗ࡞㑇 ఏᏊゎᯒࡀ㛤Ⓨࡉࢀࠊ㎿㏿࠿ࡘṇ☜࡞㑇ఏᏊデ᩿ࡀྍ⬟࡜࡞ࡗࡓࠋ

D

D. ྜే⑕

ᝏᛶ⑌ᝈࡀ㏻ᖖ 20ࠥ40 ṓ௦࡟ฟ⌧ࡍࡿࠋDCᝈ⪅࡛ࡣᝏᛶ⑌ᝈࡀ೺ᖖே࡟ẚ㍑ࡋ࡚

11ಸࡢ⨯ᝈ⋡࡜ࡉࢀ࡚࠸ࡿ⁵ࠋᡥᖹୖ⓶⒴ࠊ㦵㧊␗ᙧᡂ⑕ೃ⩌ࠊ㦵㧊ᛶⓑ⾑⑓ࡢ㢖ᗘࡀ 㧗࠸ࠋ

E. 㔜⑕ᗘศ㢮

⑌ᝈࡢ⑓ᆺ࡜ࡋ࡚ࡣࠊྂ඾ⓗ࡞DCࡢ௚࡟ࠊ᭱㔜⑕ᆺࡢHHSࠊ෌⏕୙Ⰻᛶ㈋⾑ᝈ⪅

ࡸᐙ᪘ᛶ⫵⥺⥔⑕ᝈ⪅࡟₯ࢇ࡛࠸ࡿ୙඲ᆺDCࡀᏑᅾࡍࡿࠋ㦵㧊୙඲ࡢ㔜⑕ᗘ࡜ࡋ࡚ࡣࠊ

෌⏕୙Ⰻᛶ㈋⾑ࡢ㔜⑕ᗘศ㢮࡟‽ࡌࡿࠋ

F. ἞⒪

࢔ࣥࢻࣟࢤࣥࡀ㦵㧊୙඲࡟ຠᯝࡀ࠶ࡿࡇ࡜ࡀሗ࿌ࡉࢀ࡚࠸ࡿ ⁶ࠋ࢔ࣥࢻࣟࢤࣥࡣࢸࣟ

࣓࣮ࣛࢮάᛶࢆቑຍࡉࡏࡿࡇ࡜࡛ࠊຠᯝࢆⓎ᥹ࡍࡿ࡜⪃࠼ࡽࢀ࡚࠸ࡿࠋDCᝈ⪅࡟ᑐࡋ

࡚ࠊ࢔ࣥࢻࣟࢤ࡛ࣥ࠶ࡿࢲࢼࢰ࣮ࣝࢆ1᪥800mgࠊ24࠿᭶㛫ᢞ୚ࡋࡓ➨Ϩ/ϩ┦ヨ㦂ࡢ

⤖ᯝࡀ2016ᖺ࡟ሗ࿌ࡉࢀࡓ⁷ࠋ24࠿᭶᫬Ⅼ࡛ࠊ12౛୰11౛㸦92%㸧࡛ࢸ࣓ࣟ࢔㛗ࡢ ቑຍࢆㄆࡵࠊ12౛୰10౛㸦83%㸧࡟⾑ᾮᏛⓗຠᯝࢆㄆࡵࡓࠋ᭷ᐖ஦㇟ࡣgrade2ࡲ࡛

ࡢ⫢㞀ᐖ࡜➽②ᨥࡀࡑࢀࡒࢀ41%ࠊ33%࡛࠶ࡗࡓࠋ

2016ᖺ࡟ࡣ㐣ཤࡢDCᝈ⪅࡟ᑐࡍࡿ㐀⾑ᖿ⣽⬊⛣᳜ࡢSystematic Reviewࡀሗ࿌ࡉ

ࢀࡓ⁸ࠋ5 ᖺ඲⏕Ꮡ⋡ 57%ࠊ10 ᖺ඲⏕Ꮡ⋡ 23%࡜⛣᳜ᚋᡂ⦼ࡣ୙Ⰻ࡛࠶ࡾࠊ୺࡞Ṛᅉ ࡣ⫵ྜే⑕ࠊ⏕╔୙඲ࠊឤᰁ⑕࡛࠶ࡗࡓࠋணᚋ୙ⰋᅉᏊࡣ⛣᳜᫬ᖺ㱋 20 ṓ㉸ࠊ2000 ᖺ௨๓ࡢ⛣᳜ࠊHLA୍⮴⾑⦕௨እࡢࢻࢼ࣮࡛࠶ࡗࡓࠋ⫵ྜే⑕ࡣ109౛୰15౛㸦14%㸧

࡟ㄆࡵࠊ㦵㧊㠀◚ቯⓗ๓ฎ⨨ࡀ27౛୰2౛㸦7%㸧ࠊ㦵㧊◚ቯⓗ๓ฎ⨨ࡀ71౛୰13౛ 㸦18%㸧࡛࠶ࡗࡓࠋ㦵㧊㠀◚ቯⓗ๓ฎ⨨ࡣ⫵ྜే⑕ࡀᑡ࡞࠸ഴྥࡀ࠶ࡾࠊࣇࣝࢲࣛࣅࣥ

ࢆྵࡴ㦵㧊㠀◚ቯⓗ๓ฎ⨨ࣞࢪ࣓ࣥࡀᮃࡲࡋ࠸࡜ࡉࢀࡓࠋ

௨ୖ࠿ࡽࠊ㐀⾑ᖿ⣽⬊⛣᳜ࡢᡂ⦼ࡣ୙Ⰻ࡛ࠊ⛣᳜ᚋࡣ⫵ྜే⑕ࡀᝏ໬ࡍࡿྍ⬟ᛶࡀ࠶

ࡿࡓࡵࠊDCᝈ⪅ࡢfirst line ἞⒪࡜ࡋ࡚ࡣ࢔ࣥࢻࣟࢤࣥࡀ᥎ዡࡉࢀࡿࠋࡲࡓࠊ㐀⾑ᖿ

⣽⬊⛣᳜ᚋࡢDCᝈ⪅࡟࠾࠸࡚ࡶࠊ⫵⥺⥔⑕ண㜵ࡢࡓࡵ࢔ࣥࢻࣟࢤࣥᢞ୚ࡀ᭷ຠ࡛࠶ࡿ

ྍ⬟ᛶࡀ࠶ࡿࠋ

G

G. ணᚋࠊᡂேᮇࡢㄢ㢟

DCࡢணᚋࡣࡉࡲࡊࡲ࡛࠶ࡾࠊ㐀⾑୙඲࡟ࡼࡾᗂᑡᮇ࡟ஸࡃ࡞ࡿᝈ⪅ࡀᏑᅾࡍࡿ୍᪉ࠊ 70ṓࡲ࡛⏕Ꮡࡍࡿᝈ⪅ࡶሗ࿌ࡉࢀ࡚࠸ࡿ⁹ࠋ୺࡞Ṛᅉࡣ㦵㧊୙඲ࡢ௚ࠊᝏᛶ⭘⒆ࠊ⫵⥺

⥔⑕ࡀᣲࡆࡽࢀࡿࠋ᭱ࡶ㢖ᗘࡀ㧗࠸ᝏᛶ⭘⒆ࡣ㢌㢕㒊ࡢᡥᖹୖ⓶⒴࡛࠶ࡾࠊDC࡜デ᩿

ࡉࢀࡓᝈ⪅ࡣᐃᮇⓗ࡞ࢫࢡ࣮ࣜࢽࣥࢢࡀᚲせ࡛࠶ࡿࠋ

H. デ⒪ୖὀពࡍ࡭ࡁⅬ

࢔ࣥࢻࣟࢤࣥ㸦ࢲࢼࢰ࣮ࣝ㸧἞⒪࡟ࡼࡿ๪స⏝࡜ࡋ࡚ࡣࠊ⾑ᰦ⑕ࠊ⏨ᛶ໬⑕≧ࠊ⫢ᶵ

⬟㞀ᐖࡀ࠶ࡿࠋࡲࡓࠊᡥᖹୖ⓶⒴ࠊ⾑ᾮᝏᛶ⭘⒆࡞࡝ࡢᝏᛶ⑌ᝈࡸࠊ⫵⥺⥔⑕࣭⫢◳ኚ ࡢᐃᮇⓗࢫࢡ࣮ࣜࢽࣥࢢ᳨ᰝࡀᚲせ࡛࠶ࡿࠋ

⾲㸯ඛኳᛶゅ໬୙඲⑕ࡢデ᩿ᇶ‽

$ 㦵㧊୙඲⑕

୍⣔⤫␗ᖖࡢ⾑⌫ῶᑡ࡜㦵㧊పᙧᡂࢆㄆࡵࡿ

% ኱⑕≧㸦⓶⭵࣭⢓⭷ᡤぢ㸧

⥙≧Ⰽ⣲ỿ╔

∎ࡢⴎ⦰

ཱྀ⭍⢓⭷ⓑᩬ⑕

& ᑠ⑕≧㸦ࡑࡢ௚ࡢ㌟యᡤぢ㸧 㢌㧥ࡢ႙ኻࠊⓑ㧥 ṑ∳ࡢ␗ᖖ

⫵⑓ኚ

ప㌟㛗ࠊⓎ⫱㐜ᘏ

⫢㞀ᐖ 㣗㐨⊃✽

ᝏᛶ⭘⒆ ᑠ㢌⑕

ᑠ⬻ኻㄪ 㦵⢒㧼⑕

㦵㧊୙඲࠾ࡼࡧࡘ௨ୖࡢ኱⑕≧࡜㸰ࡘ௨ୖࡢᑠ⑕≧ࢆ‶ࡓࡍ࡜

ࡁࠊ⊃⩏ࡢඛኳᛶゅ໬୙඲⑕࡜デ᩿ࡍࡿࠋ

ᅗ㸯. telomerase࡜shelterinࡢᵓ㐀

ᅗ㸰. Flow-FISHἲ࡟ࡼࡿࢸ࣓ࣟ࢔㛗 ᐃ౛

RNA template

AAUCCC

TERT

Dyskerin NOP10

NHP2

3䇻 5䇻

TERC

TTAGGG _3䇻 telomere

GAR1

5䇻

POT1 TPP1 TIN2

RAP1

TRF1 TRF2

telomerase

shelterin

ᅗ㸱. ඛኳᛶゅ໬୙඲⑕デ᩿ࡢࣇ࣮ࣟࢳ࣮ࣕࢺ

ق৵ਣિ੸؜ৈଶଝষ؜௳ઠপ෥؝ௐেௌ௮੄ఐ৾ଢ଼஢ાଓஃস୔੘ਙႈ೩৆ੁଢ଼

஢হ঵岣੔ଠਙഓ৲ਂ৸ඪ൧௜峘૞ස崔崌崱岤਴ਛফ২੝ၖග؝؟峲峴঳৖

੝૗ك

ᩥ⊩

1. Glousker G, Touzot F, Revy P, et al. Unraveling the pathogenesis of

Hoyeraal-Hreidarsson syndrome, a complex telomere biology disorder. British Journal of Haematology. 2015;170(4):457–471.

2. Walne AJ, Marrone A, Dokal I. Dyskeratosis Congenita: A Disorder of Defective Telomere Maintenance? Int J Hematol. 2005;82(3):184–189.

3. Sakaguchi H, Nishio N, Hama A, et al. Peripheral blood lymphocyte telomere length as a predictor of response to immunosuppressive therapy in childhood aplastic anemia. Haematologica. 2014;99(8):1312–1316.