Section of Virology, Department of Infectious Disease, Imperial College London, London, W2 1PG, UK.
UK Dementia Research Institute at UCL, London, UK.
J Neurovirol. 2022 Dec;28(4-6):473-482. doi: 10.1007/s13365-022-01088-x. Epub 2022 Jul 30.
Up to 3.8% of human T-lymphotropic virus type-1 (HTLV-1)-infected asymptomatic carriers (AC) eventually develop HTLV-1-associated myelopathy (HAM). HAM occurs in patients with high (> 1%) HTLV proviral load (PVL). However, this cut-off includes more than 50% of ACs and therefore the risk needs to be refined. As HAM is additionally characterised by an inflammatory response to HTLV-1, markers of T cell activation (TCA), β-microglobulin (βM) and neuronal damage were accessed for the identification of ACs at high risk of HAM. Retrospective analysis of cross-sectional and longitudinal routine clinical data examining differences in TCA (CD4/CD25, CD4/HLA-DR, CD8/CD25 & CD8/HLA-DR), βM and neurofilament light (NfL) in plasma in ACs with high or low PVL and patients with HAM. Comparison between 74 low PVL ACs, 84 high PVL ACs and 58 patients with HAM revealed a significant, stepwise, increase in TCA and βM. Construction of receiver operating characteristic (ROC) curves for each of these blood tests generated a profile that correctly identifies 88% of patients with HAM along with 6% of ACs. The 10 ACs with this 'HAM-like' profile had increased levels of NfL in plasma and two developed myelopathy during follow-up, compared to none of the 148 without this viral-immune-phenotype. A viral-immuno-phenotype resembling that seen in patients with HAM identifies asymptomatic carriers who are at increased risk of developing HAM and have markers of subclinical neuronal damage.
高达 3.8%的人类 T 淋巴细胞白血病病毒 1 型（HTLV-1）无症状感染者（AC）最终会发展为 HTLV-1 相关脊髓病（HAM）。HAM 发生在高（>1%）HTLV 前病毒载量（PVL）的患者中。然而，这一截止值包括超过 50%的 AC，因此需要对风险进行细化。由于 HAM 还伴有针对 HTLV-1 的炎症反应，因此评估 T 细胞激活标志物（TCA）、β-微球蛋白（βM）和神经元损伤，用于鉴定高风险 HAM 的 AC。对横断面和纵向常规临床数据的回顾性分析，检查了高或低 PVL 的 AC 中 TCA（CD4/CD25、CD4/HLA-DR、CD8/CD25 和 CD8/HLA-DR）、βM 和神经丝轻链（NfL）在血浆中的差异，以及 HAM 患者的差异。将 74 例低 PVL AC、84 例高 PVL AC 和 58 例 HAM 患者进行比较，发现 TCA 和βM 均呈显著、逐步增加。为这些血液检测中的每一种构建接收器操作特征（ROC）曲线，生成了一个正确识别 88%HAM 患者和 6%AC 的特征。这 10 例具有“HAM 样”特征的 AC 血浆中 NfL 水平升高，2 例在随访中发生了脊髓病，而在 148 例没有这种病毒免疫表型的患者中均未发生。与 HAM 患者相似的病毒免疫表型可识别出发生 HAM 风险增加且具有亚临床神经元损伤标志物的无症状携带者。
