Southern Brian D, Gadre Shruti K
Integrated Hospital-Care Institute, Department of Pulmonary Medicine, Cleveland Clinic, Cleveland, OH 44195, USA.
J Clin Med. 2025 Feb 24;14(5):1496. doi: 10.3390/jcm14051496.
Telomeropathies, or telomere biology disorders (TBDs), are syndromes that can cause a number of medical conditions, including interstitial lung disease (ILD), bone marrow failure, liver fibrosis, and other diseases. They occur due to genetic mutations to the telomerase complex enzymes that result in premature shortening of telomeres, the caps on the ends of cellular DNA that protect chromosome length during cell division, leading to early cell senescence and death. Idiopathic pulmonary fibrosis (IPF) is the most common manifestation of the telomere biology disorders, although it has been described in other interstitial lung diseases as well, such as rheumatoid arthritis-associated ILD and chronic hypersensitivity pneumonitis. Telomere-related mutations can be inherited or can occur sporadically. Identifying these patients and offering genetic counseling is important because telomerapathies have been associated with poorer outcomes including death, lung transplantation, hospitalization, and FVC decline. Additionally, treatment with immunosuppressants has been shown to be associated with worse outcomes. Currently, there is no specific treatment for TBD except to transplant the organ that is failing, although there are a number of promising treatment strategies currently under investigation. Shortened telomere length is routinely discovered in patients undergoing lung transplantation for IPF. Testing to detect early TBD in patients with suggestive signs or symptoms can allow for more comprehensive treatment and multidisciplinary care pre- and post-transplant. Patients with TBD undergoing lung transplantation have been reported to have both pulmonary and extrapulmonary complications at a higher frequency than other lung transplant recipients, such as graft-specific complications, increased infections, and complications related to immunosuppressive therapy.
端粒病，即端粒生物学障碍（TBDs），是一类可引发多种医学病症的综合征，包括间质性肺疾病（ILD）、骨髓衰竭、肝纤维化及其他疾病。它们是由于端粒酶复合酶发生基因突变，导致端粒过早缩短所致。端粒是细胞DNA末端的帽状结构，在细胞分裂过程中保护染色体长度，端粒缩短会导致细胞过早衰老和死亡。特发性肺纤维化（IPF）是端粒生物学障碍最常见的表现形式，不过在其他间质性肺疾病中也有描述，如类风湿关节炎相关的ILD和慢性过敏性肺炎。与端粒相关的突变可以是遗传的，也可能是散发的。识别这些患者并提供遗传咨询很重要，因为端粒病与包括死亡、肺移植、住院和用力肺活量（FVC）下降在内的较差预后相关。此外，使用免疫抑制剂治疗已被证明与更差的预后有关。目前，除了移植功能衰竭的器官外，尚无针对TBD的特异性治疗方法，不过目前有一些有前景的治疗策略正在研究中。在因IPF接受肺移植的患者中，经常发现端粒长度缩短。对有提示性体征或症状的患者进行检测以发现早期TBD，有助于在移植前后进行更全面的治疗和多学科护理。据报道，与其他肺移植受者相比，患有TBD的患者在接受肺移植时出现肺部和肺外并发症的频率更高，如移植物特异性并发症、感染增加以及与免疫抑制治疗相关的并发症。
