Haematology and Haemotherapy Department, Hospital Universitario Central de Asturias, Oviedo, Spain.
Laboratory Medicine Department, Hospital Universitario Central de Asturias, Oviedo, Spain.
Front Immunol. 2021 Oct 18;12:703256. doi: 10.3389/fimmu.2021.703256. eCollection 2021.
The exquisite coupling between herpesvirus and human beings is the result of millions of years of relationship, coexistence, adaptation, and divergence. It is probably based on the ability to generate a latency that keeps viral activity at a very low level, thereby apparently minimising harm to its host. However, this evolutionary success disappears in immunosuppressed patients, especially in haematological patients. The relevance of infection and reactivation in haematological patients has been a matter of interest, although one fundamentally focused on reactivation in the post-allogeneic stem cell transplant (SCT) patient cohort. Newer transplant modalities have been progressively introduced in clinical settings, with successively more drugs being used to manipulate graft composition and functionality. In addition, new antiviral drugs are available to treat CMV infection. We review the immunological architecture that is key to a favourable outcome in this subset of patients. Less is known about the effects of herpesvirus in terms of mortality or disease progression in patients with other malignant haematological diseases who are treated with immuno-chemotherapy or new molecules, or in patients who receive autologous SCT. The absence of serious consequences in these groups has probably limited the motivation to deepen our knowledge of this aspect. However, the introduction of new therapeutic agents for haematological malignancies has led to a better understanding of how natural killer (NK) cells, CD4+ and CD8+ T lymphocytes, and B lymphocytes interact, and of the role of CMV infection in the context of recently introduced drugs such as Bruton tyrosine kinase (BTK) inhibitors, phosphoinosytol-3-kinase inhibitors, anti-BCL2 drugs, and even CAR-T cells. We analyse the immunological basis and recommendations regarding these scenarios.
疱疹病毒与人类之间的精细耦合是数百万年相互关系、共存、适应和分歧的结果。这可能基于产生潜伏的能力，使病毒活性保持在非常低的水平，从而明显减少对宿主的伤害。然而，这种进化上的成功在免疫抑制患者中消失了，尤其是在血液学患者中。感染和再激活在血液学患者中的相关性一直是人们关注的问题，尽管人们主要关注的是同种异体干细胞移植（SCT）后患者群体中的再激活。新的移植方式已在临床环境中逐步引入，越来越多的药物被用于操纵移植物的组成和功能。此外，还有新的抗病毒药物可用于治疗 CMV 感染。我们回顾了对这部分患者产生有利结果的关键免疫学结构。对于接受免疫化疗或新型分子治疗的其他恶性血液系统疾病患者，或接受自体 SCT 的患者，关于疱疹病毒在死亡率或疾病进展方面的影响知之甚少。在这些人群中，没有严重后果的情况可能限制了深入了解这方面的动机。然而，新的血液系统恶性肿瘤治疗药物的引入使我们更好地了解自然杀伤（NK）细胞、CD4+和 CD8+T 淋巴细胞和 B 淋巴细胞之间如何相互作用，以及 CMV 感染在最近引入的药物（如 Bruton 酪氨酸激酶（BTK）抑制剂、磷酸肌醇-3-激酶抑制剂、抗 BCL2 药物，甚至 CAR-T 细胞）中的作用。我们分析了这些情况下的免疫学基础和建议。
