Ild Center of Excellence, Department of Pulmonology, St Antonius Hospital, Nieuwegein, The Netherlands.
Division of Hearth and Lungs, University Medical Center Utrecht, Utrecht, The Netherlands.
Expert Opin Ther Targets. 2022 Jan;26(1):41-55. doi: 10.1080/14728222.2022.2022123. Epub 2022 Jan 20.
Sarcoidosis is a granulomatous inflammatory disease with high chances of reduced quality of life, irreversible organ damage, and reduced life expectancy when vital organs are involved. Any organ system can be affected, and the lungs are most often affected. There is no preventive strategy as the exact etiology is unknown, and complex immunogenetic and environmental factors determine disease susceptibility and phenotype. Present-day treatment options originated from clinical practice and are effective in many patients. However, a substantial percentage of patients suffer from unacceptable side effects or still develop refractory, threatening pulmonary or extrapulmonary disease.
As non-caseating granulomas, the pathological hallmark of disease, are assigned to divergent activation and regulation of the immune system, targets in relation to the possible triggers of granuloma formation and their sequelae were reviewed.
The immunopathogenesis underlying sarcoidosis has been a dynamic field of study. Several recent new insights give way to promising new therapeutic targets, such as certain antigenic triggers (e.g. from ), mTOR, JAK-STAT and PPARγ pathways, the NRP2 receptor and MMP-12, which await further exploration. Clinical and trigger related phenotyping, and molecular endotyping will likely hold the key for precision medicine in the future.
结节病是一种肉芽肿性炎症性疾病,当涉及重要器官时,生活质量降低、器官不可逆损伤和预期寿命缩短的风险很高。任何器官系统都可能受到影响,肺部最常受到影响。由于确切的病因不明,因此没有预防策略,复杂的免疫遗传和环境因素决定了疾病的易感性和表型。目前的治疗选择源于临床实践,对许多患者有效。然而,相当一部分患者因无法接受的副作用或仍发展为难治性、威胁生命的肺部或肺外疾病而受苦。
由于非干酪样肉芽肿是疾病的病理标志,被归为免疫系统的不同激活和调节,因此对与肉芽肿形成的可能触发因素及其后果相关的靶点进行了综述。
结节病的免疫发病机制一直是一个活跃的研究领域。最近的一些新见解为有前途的新治疗靶点开辟了道路,例如某些抗原性触发因素(例如来自 )、mTOR、JAK-STAT 和 PPARγ 途径、NRP2 受体和 MMP-12,这些都有待进一步探索。临床和触发相关表型以及分子内表型可能是未来精准医学的关键。