白血球系細胞吸着療法は活動性潰瘍性大腸炎で増加する未分化樹状細胞を臨床症状とともに正常化する Leukocyte adsorptive apheresis reduces less-differentiated dendritic cells (ldDC) which increased in active ulcerative colitis

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著者

    • 宮川 浩之 MIYAKAWA Hiroyuki
    • 東京慈恵会医科大学附属青戸病院臨床工学部 Jikei University School of Medicine Aoto-General Hospital, Division of Clinical Engineering
    • 落合 秀樹 OCHIAI Hideki
    • 東京慈恵会医科大学附属青戸病院臨床工学部 Jikei University School of Medicine Aoto-General Hospital, Division of Clinical Engineering
    • 池田 雅人 IKEDA Masato
    • 東京慈恵会医科大学腎臓・高血圧内科 Jikei University School of Medicine Aoto-General Hospital, Division of Nephrology and Hypertension
    • 中尾 正嗣 NAKAO Masatsugu
    • 東京慈恵会医科大学腎臓・高血圧内科 Jikei University School of Medicine Aoto-General Hospital, Division of Nephrology and Hypertension
    • 川村 仁美 KAWAMURA Yoshimi
    • 東京慈恵会医科大学腎臓・高血圧内科 Jikei University School of Medicine Aoto-General Hospital, Division of Nephrology and Hypertension
    • 平野 景太 HIRANO Keita
    • 東京慈恵会医科大学腎臓・高血圧内科 Jikei University School of Medicine Aoto-General Hospital, Division of Nephrology and Hypertension
    • 小此木 英男 OKONOGI Hideo
    • 東京慈恵会医科大学腎臓・高血圧内科 Jikei University School of Medicine Aoto-General Hospital, Division of Nephrology and Hypertension
    • 早川 洋 HAYAKAWA Hiroshi
    • 東京慈恵会医科大学腎臓・高血圧内科 Jikei University School of Medicine Aoto-General Hospital, Division of Nephrology and Hypertension
    • 横山 啓太郎 YOKOYAMA Keitaro
    • 東京慈恵会医科大学腎臓・高血圧内科 Jikei University School of Medicine Aoto-General Hospital, Division of Nephrology and Hypertension
    • 山本 裕康 YAMAMOTO Hiroyasu
    • 東京慈恵会医科大学腎臓・高血圧内科 Jikei University School of Medicine Aoto-General Hospital, Division of Nephrology and Hypertension
    • 細谷 龍男 HOSOYA Tatsuo
    • 東京慈恵会医科大学腎臓・高血圧内科 Jikei University School of Medicine Aoto-General Hospital, Division of Nephrology and Hypertension
    • 松岡 美佳 MATSUOKA Mika
    • 東京慈恵会医科大学附属青戸病院消化器・肝臓内科 Jikei University School of Medicine Aoto-General Hospital, Division of Gastroenterology and Hepatology
    • 相澤 良夫 AIZAWA Yoshio
    • 東京慈恵会医科大学附属青戸病院消化器・肝臓内科 Jikei University School of Medicine Aoto-General Hospital, Division of Gastroenterology and Hepatology

抄録

これまでにわれわれは,白血球系細胞除去療法のうちG-CAPとL-CAPが同様に潰瘍性大腸炎(Ulcerative colitis:UC)の末梢血液中の樹状細胞(dendritic cell:DC)Subset比率に影響を与えることを報告した<SUP>1)</SUP>.今回,UCで増加する病因細胞をスクリーニングするため,UC症例と健常人で末梢血樹状細胞のサブセット解析を施行した.総樹状細胞(Total DCs)は末梢血有核細胞の4 color FACS解析によりLineage marker(CD3, CD14, CD16, CD19, CD20 and CD56)陰性,かつHLA-DR陽性の細胞として同定され,このTotal DCsはさらにCD11CとCD123の反応性によりDC1,DC2,less differentiated DC:ldDCの各DCサブセットに分類された.末梢血液中のFACS解析の結果,DC SubsetのうちldDCについては吸着療法施行前のUC患者では健常者に比較して有意に増加していた(p<0.03).次にldDCがUCの活動性調節細胞である可能性を検討するため,DC細胞数に影響を与える免疫抑制剤(グルココルチコイド)投与量を一定(30±10mg/body)に保ったうえで白血球系細胞吸着療法(L-CAP 6例,G-CAP 6例)を施行したUC症例12例(男性3例,女性9例)を対象に,各DC Subsetの経時変化を検討した.12例中,瀬尾activity index 50点以上低下が得られた白血球系細胞吸着療法の有効例は8例,残りの4例は無効であった.有効例では治療経過とともにldDCは徐々に減少し,最終回には有意な低下が認められ,健常者と同等レベルまで正常化した.一方,吸着療法の無効例では,ldDCは持続高値のままで有意な変化を認めなかった.一方,DC Subsetのうち総DC数,DC1,DC2はUC患者と健常人の比較で有意差を認めず,吸着療法前後で有意な変化を認めなかった.以上から潰瘍性大腸炎で増加する末梢血液中のldDCは,免疫抑制剤の投与量変更なしで白血球系細胞吸着療法により臨床症状とともに正常化することから,UCの活動性調節細胞である可能性が示された.

Leukocyte adsorptive apheresis (L-CAP and G-CAP) is an effective treatment for ulcerative colitis (UC). We reported that leukocyte absorption might influence blood dendritic cell subsets constitution in UC patients <SUP>1)</SUP>. In this study, we aimed to clarify how DC subsets change during the leukocyte adsorptive apheresis session against active UC. Twelve active UC patients were enrolled in this study. These patients received either 6 or 11 sessions of leukocyte adsorptive apheresis and 3,000mL of whole blood was evenly processed at each leukocyte absorption session. All patients received prednisolone at a dose of 30±10mg/body before leukocyte adsorptive apheresis and each dose did not change during the whole leukocyte adsorptive apheresis session. Peripheral blood samples were examined at every first, 3rd, 6th and 11th leukocyte adsorptive apheresis session. Using 4 colors FACS, total DC were captured as negative for Lineage marker (CD3, CD14, CD16, CD19, CD20 and CD56) and positive for HLA-DR. Next, total DC were divided into DC subsets as DC1, DC2 and less-differentiated DC (ldDC) by reactivity of CD11C and CD123 antibody. Above 50 points decreases by Seo activity index was evaluated as the effective group. Therapeutic effectiveness was obtained in 8 of 12 UC patients and the DC subsets were compared to those of healthy volunteers, the leukocyte adsorptive apheresis-effective group and leukocyte adsorptive apheresis-ineffective group. Total DC, DC1 and DC2 did not significantly differ between healthy volunteers and UC patients, and did not significantly change during the leukocyte adsorptive apheresis session. However, the ldDC concentration before leukocyte adsorptive apheresis was significantly higher in UC patients than in healthy volunteers (p<0.03) and significantly decreased toward the healthy control level after the final leukocyte adsorptive apheresis session in the leukocyte adsorptive apheresis-effective group. These outcomes indicate that leukocyte adsorptive apheresis reduces less-differentiated dendritic cells (ldDC), which are increased in active ulcerative colitis.

収録刊行物

  • 日本透析医学会雑誌 = Journal of Japanese Society for Dialysis Therapy  

    日本透析医学会雑誌 = Journal of Japanese Society for Dialysis Therapy 41(2), 119-126, 2008-02-28 

    The Japanese Society for Dialysis Therapy

参考文献:  19件

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各種コード

  • NII論文ID(NAID)
    10021274317
  • NII書誌ID(NCID)
    AN10432053
  • 本文言語コード
    JPN
  • 資料種別
    ART
  • ISSN
    13403451
  • NDL 記事登録ID
    9398392
  • NDL 雑誌分類
    ZS39(科学技術--医学--皮膚科学・泌尿器科学)
  • NDL 請求記号
    Z19-1413
  • データ提供元
    CJP書誌  NDL  J-STAGE 
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