The Global Tuberculosis Program, Texas Children's Hospital, Immigrant and Global Health, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.
Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, USA.
Med. 2021 Mar 12;2(3):217-232. doi: 10.1016/j.medj.2020.11.003. Epub 2021 Jan 16.
There is hope that host-directed therapy (HDT) for Tuberculosis (TB) can either shorten treatment duration, help cure drug resistant disease or limit the immunopathology. Many candidate HDT drugs have been proposed, however solid evidence only exists for a few select patient groups. The clinical presentation of TB is variable, with differences in severity, tissue pathology, and bacillary burden. TB clinical phenotypes likely determine the potential benefit of HDT. Underlying TB clinical phenotypes, there are TB "endotypes," defined as distinct molecular profiles, with specific metabolic, epigenetic, transcriptional, and immune phenotypes. TB endotypes can be characterized by either immunodeficiency or pathologic excessive inflammation. Additional factors, like comorbidities (HIV, diabetes, helminth infection), structural lung disease or virulence also drive TB endotypes. Precise disease phenotyping, combined with in-depth immunologic and molecular profiling and multimodal omics integration, can identify TB endotypes, guide endotype-specific HDT, and improve TB outcomes, similar to advances in cancer medicine.
人们希望针对结核病（TB）的宿主导向治疗（HDT）能够缩短治疗时间、帮助治愈耐药疾病或限制免疫病理学。已经提出了许多候选 HDT 药物，但只有少数特定患者群体存在确凿的证据。TB 的临床表现多种多样，严重程度、组织病理学和细菌负荷存在差异。TB 临床表型可能决定 HDT 的潜在获益。在 TB 临床表型之下，存在 TB“内型”，定义为具有特定代谢、表观遗传、转录和免疫表型的独特分子谱。TB 内型可以通过免疫缺陷或病理性过度炎症来表征。其他因素，如合并症（HIV、糖尿病、寄生虫感染）、结构性肺病或毒力，也会导致 TB 内型。精确的疾病表型、结合深入的免疫和分子分析以及多模态组学整合，可以识别 TB 内型，指导针对内型的 HDT，并改善 TB 结局，类似于癌症医学的进展。
