Department of Rheumatology, Hospital Universitario 12 de Octubre, Instituto de Investigación Hospital 12 de Octubre (imas12), Madrid, Spain.
Department of Microbiology, Instituto de Investigación INCLIVA, Hospital Clínico, Valencia, Spain.
Semin Arthritis Rheum. 2020 Feb;50(1):166-171. doi: 10.1016/j.semarthrit.2019.06.019. Epub 2019 Jun 29.
Torque teno virus (TTV) is a highly prevalent non-pathogenic anellovirus whose plasma levels may be a biomarker of immunosuppression. The aim of this study was to assess whether specific immune-targeting with different biologic drugs may differentially modulate TTV viremia in arthritis patients.
TTV DNA load was quantified by PCR in a cross-sectional sample of 79 patients with chronic arthritis on biologic therapy (abatacept, infliximab, rituximab or tocilizumab), 31 patients treated with conventional DMARDs (methotrexate and/or leflunomide), and 54 healthy individuals. Longitudinal changes in TTV load were analysed in a second group of 59 patients at baseline and 4-months after biologic therapy. Correlations between clinical or biological characteristics of recruited patients and TTV viremia were also analysed.
In the cross-sectional study, TTV load was significantly higher in patients who received abatacept, infliximab or tocilizumab compared to healthy individuals. Patients treated with rituximab or conventional DMARDs showed TTV loads similar to healthy controls. In the longitudinal study, an increase in the TTV load was observed after anti-TNF, tocilizumab, abatacept and rituximab, but not after secukinumab therapy. Correlations between TTV load and clinical variables such as disease duration, concomitant glucocorticoid or DMARDs therapy, lymphocytes or previous infections were not found. A non-significant trend towards higher TTV load was observed in therapy responders.
Patients with chronic arthritis on biologic but not on conventional DMARD or anti-IL17 therapy have increased TTV viremia. This observation provides a basis to prospectively explore the potential value of TTV load as a potential pharmacodynamic biomarker.
Torque teno 病毒(TTV)是一种高度流行的非致病性微小病毒,其血浆水平可能是免疫抑制的生物标志物。本研究旨在评估不同生物药物的特异性免疫靶向治疗是否会对关节炎患者的 TTV 病毒血症产生不同的调节作用。
在接受生物治疗(阿巴西普、英夫利昔单抗、利妥昔单抗或托珠单抗)的 79 例慢性关节炎患者、接受传统 DMARDs(甲氨蝶呤和/或来氟米特)治疗的 31 例患者和 54 名健康个体的横断面样本中,通过 PCR 定量检测 TTV DNA 载量。在第二组 59 例患者中分析基线和生物治疗后 4 个月时 TTV 载量的纵向变化。还分析了招募患者的临床或生物学特征与 TTV 病毒血症之间的相关性。
在横断面研究中,接受阿巴西普、英夫利昔单抗或托珠单抗治疗的患者的 TTV 载量明显高于健康个体。接受利妥昔单抗或传统 DMARDs 治疗的患者的 TTV 载量与健康对照组相似。在纵向研究中,抗 TNF、托珠单抗、阿巴西普和利妥昔单抗治疗后观察到 TTV 载量增加,但 secukinumab 治疗后未观察到增加。未发现 TTV 载量与疾病持续时间、同时使用糖皮质激素或 DMARDs 治疗、淋巴细胞或先前感染等临床变量之间存在相关性。在治疗反应者中观察到 TTV 载量升高的趋势,但无统计学意义。
接受生物治疗而非传统 DMARD 或抗 IL17 治疗的慢性关节炎患者 TTV 病毒血症增加。这一观察结果为前瞻性探索 TTV 载量作为潜在药效动力学生物标志物的潜在价值提供了依据。