神经结节病,一种罕见的肉芽肿病,引起炎症和中枢神经系统(CNS)的损伤。神经结节病的主要诊断挑战是缺乏明确定义的生物标志物。如果组织病理学无法接近或不确定,则需要活检进行诊断可能会导致延误和误诊。强调需要更容易获得的诊断指标。目前“明确的”神经结节病诊断的金标准需要对中枢神经系统组织进行活检,显示非干酪样肉芽肿。然而,这种活检具有固有的侵入性,并具有相关的手术风险。值得注意的是,血管紧张素转换酶(ACE),通常与系统性结节病有关,由于在中枢神经系统受累的情况下缺乏准确性,因此被认为是神经结节病的不良生物标志物。此外,神经结节病的影像学,虽然广泛使用,对缩小诊断范围很重要,缺乏特异性。数十年的研究已经产生了分子和免疫生物标志物-可溶性白细胞介素-2受体(IL-2R),血清淀粉样蛋白A1,CD4/CD8比值,新蝶呤,干扰素-γ(IFN-γ),和趋化因子配体2(CCL2)-具有提高诊断准确性的潜力。然而,这些生物标志物在临床治疗中尚未建立,因为它们可能难以获得,并且来自小型研究.它们还缺乏对其它炎性和感染性中枢神经系统疾病的特异性。需要新的生物标志物与先前发现的生物标志物一起使用,以改善这种罕见疾病的诊断。这篇综述综合了现有的关于神经结节病生物标志物的文献,旨在为这一不断发展的领域的进一步研究奠定基础。它还巩固了系统性结节病的生物标志物的信息,例如尚未在神经结节病中进行研究的IL-8和可溶性CD40L,但具有作为CNS疾病标志物的潜力。
Neurosarcoidosis, a rare granulomatous disease, causes inflammation and damage to the central nervous system (CNS). A major diagnostic challenge in
neurosarcoidosis is the absence of well-defined biomarkers. The need for biopsy to make the diagnosis can lead to delays and misdiagnosis if histopathology is inaccessible or indeterminate, highlighting the need for more accessible diagnostic indicators. The current gold standard for a \"definite\"
neurosarcoidosis diagnosis requires biopsy of CNS tissue revealing non-caseating granulomas. However, such biopsies are inherently invasive and carry associated procedural risks. Notably, angiotensin-converting enzyme (ACE), commonly associated with systemic sarcoidosis, is recognized as a poor biomarker for neurosarcoidosis due to its lack of accuracy in the context of CNS involvement. Furthermore, imaging in
neurosarcoidosis, while widely utilized and important for narrowing the diagnosis, lacks specificity. Decades of research have yielded molecular and immunologic biomarkers-soluble interleukin-2 receptor (IL-2R), serum amyloid A1, the CD4/CD8 ratio, neopterin, interferon-gamma (IFN-γ), and chemokine ligand 2 (CCL2)-that hold potential for improving diagnostic accuracy. However, these biomarkers are not yet established in clinical care as they may be difficult to obtain and are derived from small studies. They also suffer from a lack of specificity against other inflammatory and infectious central nervous system diseases. New biomarkers are needed for use alongside those previously discovered to improve diagnosis of this rare disease. This review synthesizes existing literature on
neurosarcoidosis biomarkers, aiming to establish a foundation for further research in this evolving field. It also consolidates information on biomarkers of systemic sarcoidosis such as IL-8 and soluble CD40L that have not yet been studied in neurosarcoidosis but hold potential as markers of CNS disease.