ANCAに関連した血管炎におけるCD4+CD28- T細胞拡張と動脈硬化との関連:ランダム化比較試験からの基値データ
Dimitrios Chanouzas1, Lovesh Dyall1, Jessica Dale1
1School of Immunity and Infection, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK.
Lancet (London, England)
|August 28, 2015
まとめ
細胞メガロウイルス (CMV) の抗中性細胞体抗体関連血管炎 (AAV) の患者は,心血管疾患のリスクが増加しています. CD4+CD28- T細胞は動脈の硬化に関連しており,ヴァラシクロビールの治療はこれらの細胞を減少させた.
科学分野:
- 免疫学
- 心血管医学
- ウイルス学
背景:
- 抗中性子細胞体抗体 (ANCA) と関連した血管系抗体 (AAV) は心血管疾患のリスクを高めます.
- CD4+CD28- T細胞は,細胞メガロウイルス (CMV) 陽性であるAAV患者で拡張し,死亡率と動脈の硬化と相関しています.
研究 の 目的:
- CMV陽性AAV患者におけるCD4+CD28- T細胞と動脈の硬化との関連性を評価する.
- ヴァラシクロビールの治療がCD4+CD28- T細胞の集団を減少させるかどうかを判断する.
主な方法:
- オープンフェーズ2試験では,28人のAAV患者をランダムにヴァラシクロヴィルまたは6ヶ月間追加治療を受けさせました.
- 動脈の硬直度 (PWV) を測定し,CD4+CD28- T細胞とIFNγ分泌をフローサイトメトリーで分析した.
- CD4+CD28- T細胞とPWVの相関性を評価し,治療意図分析を行った.
主要な成果:
- CD4+CD28- T細胞は,CD4+CD28+T細胞と比較して,より高いT- ベット発現とIFNγ分泌を示した.
- 内皮機能障害のマーカーであるCX3CR1は,CD4+CD28- T細胞のみで発現した.
- PWVと相関するCD4+CD28- T細胞の割合 (r=0. 408, p=0. 035);バラシクロビール治療はこれらの細胞を著しく減少させた.
結論:
- AAVのCD4+CD28- T細胞は炎症を誘発し,CX3CR1を発現し,動脈の硬化に関連しています.
- ヴァラシクロビールの治療はCD4+CD28- T細胞の膨張を弱める.
- AAVの死亡率における心血管疾患の役割を考えると,この発見は重要だ.
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