同種造血細胞移植後ヒトヘルペスウイルス6型の再活性化の免疫学的機序の解明

Material type: 文書・図像類

Author: 山崎, 理絵

Publisher: 慶應義塾大学

Publication date: 2019

Material Format: Digital

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Note (General)：: type:text【背景】同種造血幹細胞移植後(HSCT)のヒトヘルペスウイルス6型(human herpesvirus 6: HHV-6）の再活性化は、重篤な中枢神経合併症を引き起こすが、そのリスク因子に関しては不明な点が多い。【概要】まずHSCT患者34例を対象に、デジタルPCR及びリアルタイ...

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Material Type: 文書・図像類
Title: 同種造血細胞移植後ヒトヘルペスウイルス6型の再活性化の免疫学的機序の解明
Author/Editor: 山崎, 理絵
Author Heading: 山崎, 理絵
Publication, Distribution, etc.: 慶應義塾大学
Publication Date: 2019
Publication Date (W3CDTF): 2019
Alternative Title: ドウシュゾウケツサイボウイショクゴヒトヘルペスウイルス 6ガタノサイカッセイカノメンエキガクテキキジョノカイメイ
Dōshu zōketsu saibō ishokugo hito herupesuuirusu 6gata no saikasseika no men'ekigakuteki kijo no kaimei
HHV-6 reactivation and its association with dynamics of CD134-positive T cells after allogeneic hematopoetic stem cell transplantation.
Periodical title: 学事振興資金研究成果実績報告書
Text Language Code: jpn
eng
Target Audience: 一般
Note (General): type:text
【背景】同種造血幹細胞移植後(HSCT)のヒトヘルペスウイルス6型(human herpesvirus 6: HHV-6）の再活性化は、重篤な中枢神経合併症を引き起こすが、そのリスク因子に関しては不明な点が多い。【概要】まずHSCT患者34例を対象に、デジタルPCR及びリアルタイムPCRを用いて血漿中のHHV-6 DNA量を測定し、CD4+ T細胞におけるHHV-6Bの特異的受容体であるCD134発現率とHHV-6再活性化の関連について前向きに検討した。HHV-6再活性化群では非再活性化群と比較して移植前のCD4+ T細胞におけるCD134発現率(CD134/CD4比)が有意に高値であった(3.8% [0.4–25.6] vs. 1.5% [0.4–3.7], P < 0.01）。多変量解析では、移植前にCD134/CD4比が高い症例(odds比 = 10.5, 95%信頼区間: 1.3–85.1; P = 0.03）と、臍帯血移植を含むHLA不適合移植において(odds比= 15.4, 95%信頼区間: 2.0–121.0; P = 0.04）、移植後HHV-6再活性化のリスクが有意に増加することが判明した。さらに対象症例を増やし109例について移植前のCD134+CD4+T細胞の絶対数を調べたところ、high copy数の活性化あるいはHHV-6関連CNS合併症をきたし治療を必要とした症例(要治療群：N = 10）において、治療不要群(N = 99）に比べ移植前のCD134+CD4+T細胞の絶対数が有意に多いことが確認された(8.1/μl[2.8–78.7] vs. 2.1/μl[0.02-75.5], P = 0.01)。多変量解析でも、移植前のCD134+CD4+細胞の絶対数が高い症例において、移植後治療を必要とするような重篤なHHV-6再活性化を起こすリスクが有意に高いことが判明した。(odds比= 16.9, 95%信頼区間: 1.8–159.0; P = 0.01）【結語】移植後のHHV-6再活性化のリスク因子として、移植前のCD134/CD4比が高値であることを同定した。さらに、重症化のリスク因子としてCD134+CD4+T細胞の絶対数高値が同定され、移植前のCD134+CD4+T細胞数モニタリングにより、移植後HHV6再活性化および重症化を予測することができると考えられた。 Background: Human herpesvirus 6 (HHV-6) causes life-threatening central nervous system disorders after allogeneic hematopoietic stem cell transplantation (allo-HSCT). We prospectively evaluated the relationship between HHV-6 reactivation and CD134+ T cells in the recipients of allo-HSCT. Methods and Results: First, HHV-6 viral load in plasma was quantitatively measured weekly after allo-HSCT by digital polymerase chain reaction in 34 patients. The ratio of CD134 in CD4+ T cells (CD134/CD4 ratio) was serially measured by flow cytometry before and after HSCT. The CD134/CD4 ratio before HSCT was significantly higher in patients with HHV-6 reactivation than in those without (median, 3.8% vs 1.5%, P < 0.01). In multivariate analysis, a higher CD134/CD4 ratio before HSCT was significantly associated with the incidence of HHV-6 reactivation (odds ratio, 10.5 [95% confidence interval, 1.3-85.1], P = 0.03). Second, CD134+CD4+ T cell absolute count before HSCT was measured in 109 patients. HHV-6 viral load was measured only by real-time quantitative polymerase chain reaction (qPCR).HHV-6 was detected in 48 patients. Ten patients developed severe HHV-6 reactivation which needed antiviral therapy: 5 were preemptively treated for high copy numbers of HHV-6 DNA and 5 were therapeutically treated for HHV-6 related CNS disorder. CD134+CD4+ T cell count before HSCT was significantly higher in patients with necessity of antiviral therapy (N=10)than those without (N = 99) (8.1/μl [2.8–78.7] vs. 2.1/μl [0.02-75.5], P = 0.01). In multivariate analysis, higher CD4+CD134+ T cell count before HSCT remained to be significantly associated with the incidence of severe HHV-6 reactivation (odds ratio = 16.9, 95% confidence interval: 1.8–159.0, P = 0.01). Conclusions: A higher CD134/CD4 ratio was associated with a higher risk of HHV-6 reactivation. Furthermore, higher count of CD134+CD4+ cells before HSCT was associated with a higher risk of treatment-requierd severe HHV6-reactivation, suggesting that monitoring of CD134+CD4+ cells may be a promising marker for predicting treatment- requierd HHV-6 reactivation after allo-HSCT.
Source: https://koara.lib.keio.ac.jp/xoonips/modules/xoonips/download.php?koara_id=2019000007-20190007
https://koara.lib.keio.ac.jp/xoonips/modules/xoonips/download.php?koara_id=2019000007-20190007
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Data Provider (Database): 国立情報学研究所 : 学術機関リポジトリデータベース（IRDB）（機関リポジトリ）
https://irdb.nii.ac.jp
Original Data Provider (Database): 慶應義塾大学 : 慶應義塾大学学術情報リポジトリ