血清胶质纤维酸性蛋白与多发性硬化症脑部表达TSPO的病灶相关。
Serum glial fibrillary acid protein associates with TSPO-expressing lesions in multiple sclerosis brain.
作者信息
Sjöros Tanja, Saraste Maija, Matilainen Markus, Nylund Marjo, Koivumäki Mikko, Kuhle Jens, Leppert David, Airas Laura
机构信息
Turku PET Centre, University of Turku, Åbo Akademi University, Turku University Hospital, P.O. Box 52, Turku 20521, Finland.
Clinical Neurosciences, University of Turku, Turku, Finland InFLAMES Research Flagship, University of Turku, Turku, Finland.
出版信息
Ther Adv Neurol Disord. 2025 Jul 28;18:17562864251352998. doi: 10.1177/17562864251352998. eCollection 2025.
BACKGROUND
Serum glial fibrillary acidic protein (sGFAP) is a promising biomarker for multiple sclerosis (MS) disease progression. Elevated sGFAP levels are considered to reflect ongoing astrocyte-related pathology in the central nervous system.
OBJECTIVES
To study whether sGFAP levels associate with 18 kDa translocator protein (TSPO) availability in MS brain. TSPO is a mitochondrial molecule that is expressed by activated microglia and astrocytes.
DESIGN
Cross-sectional multimodal biomarker correlation study.
METHODS
We included 80 people with MS (66 relapsing-remitting and 14 progressive MS, 69% women), and 11 healthy control participants (73% women). sGFAP was measured using single molecule array (Simoa®) technology in combination with 3T magnetic resonance imaging and positron emission tomography (PET) using a TSPO-binding [C]PK11195 radioligand.
RESULTS
sGFAP was higher among people with progressive MS (median 122 pg/ml) compared to healthy controls (median 59 pg/ml, = 0.0002) or participants with relapsing-remitting MS (median 77 pg/ml, = 0.0056). Among people with MS, higher sGFAP associated with higher volume of chronic lesions with increased TSPO activity ( = 0.36, = 0.0011) and with thalamic TSPO activity ( = 0.30, = 0.0069), as well as with T1 and T2 lesion loads ( = 0.38, 0.41, = 0.0005, 0.0002, respectively). Smaller normal-appearing white matter ( = -0.36, = 0.0009), cortical gray matter, and thalamus volumes ( = -0.39, = 0.0003 for both) correlated with higher sGFAP. In regression analyses, the volume of TSPO-expressing lesions, together with age and MS disease-modifying treatment status, explained 27% of the variation in sGFAP.
CONCLUSION
sGFAP associates with adverse magnetic resonance imaging and PET imaging outcomes. The association between a high prevalence of TSPO-expressing white matter lesions and high sGFAP suggests that lesion-associated glial activity promotes MS progression partially via astrocyte-driven mechanisms. A combination of various soluble biomarkers and PET ligands for specific cell types may add to the understanding of progression-promoting cellular mechanisms in the brain.
TRIAL REGISTRATION
ClinicalTrials.gov NCT03134716, NCT03368677, NCT04126772, NCT04239820, https://clinicaltrials.gov.
背景
血清胶质纤维酸性蛋白（sGFAP）是一种用于评估多发性硬化症（MS）疾病进展的有前景的生物标志物。sGFAP水平升高被认为反映了中枢神经系统中正在进行的与星形胶质细胞相关的病理变化。
目的
研究sGFAP水平是否与MS脑内18 kDa转运蛋白（TSPO）的可用性相关。TSPO是一种线粒体分子，由活化的小胶质细胞和星形胶质细胞表达。
设计
横断面多模态生物标志物相关性研究。
方法
我们纳入了80例MS患者（66例复发缓解型和14例进展型MS，69%为女性）和11名健康对照参与者（73%为女性）。使用单分子阵列（Simoa®）技术结合3T磁共振成像和正电子发射断层扫描（PET），采用TSPO结合型[C]PK11195放射性配体测量sGFAP。
结果
与健康对照（中位数59 pg/ml，=0.0002）或复发缓解型MS参与者（中位数77 pg/ml，=0.0056）相比，进展型MS患者的sGFAP更高（中位数122 pg/ml）。在MS患者中，较高的sGFAP与TSPO活性增加的慢性病变体积较大（=0.36，=0.0011）、丘脑TSPO活性较高（=0.30，=0.0069）以及T1和T2病变负荷较高（分别为=0.38，0.41，=0.0005，0.0002）相关。正常外观白质体积较小（=-0.36，=0.0009）、皮质灰质和丘脑体积较小（两者均为=-0.39，=0.0003）与较高的sGFAP相关。在回归分析中，表达TSPO的病变体积，连同年龄和MS疾病修饰治疗状态，解释了sGFAP变异的27%。
结论
sGFAP与不良的磁共振成像和PET成像结果相关。表达TSPO的白质病变高患病率与高sGFAP之间的关联表明，病变相关的胶质细胞活性部分通过星形胶质细胞驱动的机制促进MS进展。多种可溶性生物标志物和针对特定细胞类型的PET配体的组合可能有助于加深对大脑中促进疾病进展的细胞机制的理解。
试验注册
ClinicalTrials.gov NCT0３134716、NCT03368677、NCT04126772、NCT04239820，https://clinicaltrials.gov 。
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