文章：

对人类T细胞白血病病毒1型携带者中的T细胞克隆性进行定量，可早期发现成人T细胞白血病的发生

Quantification of T cell clonality in human T cell leukaemia virus type-1 carriers can detect the development of adult T cell leukaemia early

原文发布日期：2021-03-26

DOI: 10.1038/s41408-021-00458-8

类型: Article

开放获取: 是

英文摘要：

Adult T cell leukaemia/lymphoma (ATL) arises from clonally expanded T cells that are infected with human T cell leukaemia virus type-1 (HTLV-1). Here, we show that ATL can be detected early in HTLV-1-carriers through quantification of T-cell receptor (TCR)Vβ subunit diversity on T-cells infected with HTLV-1 (CD3+ CCR4+ CD26− T-cells) using an ‘oligoclonality index’ (OCI-flow). We established a reference range for OCI-flow by analysing peripheral blood mononuclear cells (PBMCs) from HTLV-1-carriers who had not developed ATL in a median of 10.5 years follow up (n = 38) and patients with ATL (n = 30). In the third cohort of HTLV-1-carriers with no history or clinical evidence of ATL (n = 106), 19% of high proviral load (PVL, ≥4 copies of HTLV-1/100 PBMCs) carriers had an OCI-flow in the ATL range, >0.770. Carriers with an OCI-flow >0.770 (n = 14) had higher lymphocyte counts and PVLs and were more likely to have a family history of ATL than carriers with OCI-flow ≤0.770. ATL subsequently developed in two of these 14 carriers but no carriers with OCI-flow ≤0.770 (p = 0.03, cumulative follow-up 129 person-years). This method can be used to identify a subset of high-PVL HTLV-1-carriers at increased risk of developing ATL who may benefit from intervention therapy, prior to the detection of disease.
 

摘要翻译： 

成人T细胞白血病/淋巴瘤（ATL）源于克隆性扩增的人类T细胞白血病病毒1型感染T细胞。本研究通过使用“寡克隆性指数”流式检测技术（OCI-flow），定量分析HTLV-1感染T细胞（CD3+ CCR4+ CD26− T细胞）的T细胞受体Vβ亚基多样性，证明可在HTLV-1携带者中实现ATL的早期检测。我们通过分析中位随访10.5年未发展为ATL的HTLV-1携带者（n=38）及ATL患者（n=30）的外周血单个核细胞，建立了OCI-flow的参考区间。在第三组无ATL病史或临床证据的HTLV-1携带者中（n=106），19%的高前病毒载量携带者（≥4个HTLV-1拷贝/100个PBMCs）的OCI-flow值处于ATL范围（>0.770）。与OCI-flow≤0.770的携带者相比，OCI-flow>0.770的携带者（n=14）淋巴细胞计数和前病毒载量更高，且更可能具有ATL家族史。在这14名携带者中，后续有2人发展为ATL，而OCI-flow≤0.770的携带者无人发病（p=0.03，累计随访129人年）。该方法可在疾病检出前识别出高前病毒载量HTLV-1携带者中ATL风险升高的亚群，这类人群可能受益于干预性治疗。

原文链接：

Quantification of T cell clonality in human T cell leukaemia virus type-1 carriers can detect the development of adult T cell leukaemia early