Tanja Sjöros, Maija Saraste, Markus Matilainen, Marjo Nylund, Mikko Koivumäki, Jens Kuhle, David Leppert, Laura Airas
{"title":"多发性硬化症脑组织中血清胶质原纤维酸蛋白与tspo表达病变相关。","authors":"Tanja Sjöros, Maija Saraste, Markus Matilainen, Marjo Nylund, Mikko Koivumäki, Jens Kuhle, David Leppert, Laura Airas","doi":"10.1177/17562864251352998","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Objectives: </strong>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.</p><p><strong>Design: </strong>Cross-sectional multimodal biomarker correlation study.</p><p><strong>Methods: </strong>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 [<sup>11</sup>C]PK11195 radioligand.</p><p><strong>Results: </strong>sGFAP was higher among people with progressive MS (median 122 pg/ml) compared to healthy controls (median 59 pg/ml, <i>p</i> = 0.0002) or participants with relapsing-remitting MS (median 77 pg/ml, <i>p</i> = 0.0056). Among people with MS, higher sGFAP associated with higher volume of chronic lesions with increased TSPO activity (<i>r</i> = 0.36, <i>p</i> = 0.0011) and with thalamic TSPO activity (<i>r</i> = 0.30, <i>p</i> = 0.0069), as well as with T1 and T2 lesion loads (<i>r</i> = 0.38, 0.41, <i>p</i> = 0.0005, 0.0002, respectively). Smaller normal-appearing white matter (<i>r</i> = -0.36, <i>p</i> = 0.0009), cortical gray matter, and thalamus volumes (<i>r</i> = -0.39, <i>p</i> = 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.</p><p><strong>Conclusion: </strong>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.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov NCT03134716, NCT03368677, NCT04126772, NCT04239820, https://clinicaltrials.gov.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"18 ","pages":"17562864251352998"},"PeriodicalIF":4.1000,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12314351/pdf/","citationCount":"0","resultStr":"{\"title\":\"Serum glial fibrillary acid protein associates with TSPO-expressing lesions in multiple sclerosis brain.\",\"authors\":\"Tanja Sjöros, Maija Saraste, Markus Matilainen, Marjo Nylund, Mikko Koivumäki, Jens Kuhle, David Leppert, Laura Airas\",\"doi\":\"10.1177/17562864251352998\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>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.</p><p><strong>Objectives: </strong>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.</p><p><strong>Design: </strong>Cross-sectional multimodal biomarker correlation study.</p><p><strong>Methods: </strong>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 [<sup>11</sup>C]PK11195 radioligand.</p><p><strong>Results: </strong>sGFAP was higher among people with progressive MS (median 122 pg/ml) compared to healthy controls (median 59 pg/ml, <i>p</i> = 0.0002) or participants with relapsing-remitting MS (median 77 pg/ml, <i>p</i> = 0.0056). Among people with MS, higher sGFAP associated with higher volume of chronic lesions with increased TSPO activity (<i>r</i> = 0.36, <i>p</i> = 0.0011) and with thalamic TSPO activity (<i>r</i> = 0.30, <i>p</i> = 0.0069), as well as with T1 and T2 lesion loads (<i>r</i> = 0.38, 0.41, <i>p</i> = 0.0005, 0.0002, respectively). Smaller normal-appearing white matter (<i>r</i> = -0.36, <i>p</i> = 0.0009), cortical gray matter, and thalamus volumes (<i>r</i> = -0.39, <i>p</i> = 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.</p><p><strong>Conclusion: </strong>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.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov NCT03134716, NCT03368677, NCT04126772, NCT04239820, https://clinicaltrials.gov.</p>\",\"PeriodicalId\":22980,\"journal\":{\"name\":\"Therapeutic Advances in Neurological Disorders\",\"volume\":\"18 \",\"pages\":\"17562864251352998\"},\"PeriodicalIF\":4.1000,\"publicationDate\":\"2025-07-28\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12314351/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Therapeutic Advances in Neurological Disorders\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1177/17562864251352998\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/1/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q1\",\"JCRName\":\"CLINICAL NEUROLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Therapeutic Advances in Neurological Disorders","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1177/17562864251352998","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/1 0:00:00","PubModel":"eCollection","JCR":"Q1","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
引用次数: 0
摘要
背景：血清胶质原纤维酸性蛋白（sGFAP）是一种很有前景的多发性硬化症（MS）疾病进展的生物标志物。sGFAP水平升高被认为反映了中枢神经系统中星形胶质细胞相关的病理。目的：研究sGFAP水平是否与MS脑中18kda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名多发性硬化症患者（66名复发缓解型和14名进展型多发性硬化症患者，69%为女性）和11名健康对照患者（73%为女性）。sGFAP采用单分子阵列（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[11C]PK11195放射配体。结果：进展性MS患者（中位数122 pg/ml）的sGFAP高于健康对照组（中位数59 pg/ml， p = 0.0002）或复发-缓解型MS患者（中位数77 pg/ml， p = 0.0056）。在MS患者中，较高的sGFAP与TSPO活性增加的慢性病变体积增加（r = 0.36, p = 0.0011）、丘脑TSPO活性增加（r = 0.30, p = 0.0069）以及T1和T2病变负荷增加相关（r = 0.38, 0.41, p = 0.0005, 0.0002）。较小的正常白质（r = -0.36, p = 0.0009）、皮质灰质和丘脑体积（r = -0.39, p = 0.0003）与较高的sGFAP相关。在回归分析中，表达tspo的病变体积、年龄和MS疾病改善治疗状态解释了27%的sGFAP变异。结论：sGFAP与不良的磁共振成像和PET成像结果相关。高表达tspo的白质病变患病率与高sGFAP之间的关联表明，病变相关的胶质活性部分通过星形胶质细胞驱动机制促进MS进展。针对特定细胞类型的各种可溶性生物标志物和PET配体的组合可能有助于理解大脑中促进进展的细胞机制。试验注册：ClinicalTrials.gov NCT03134716, NCT03368677, NCT04126772, NCT04239820, https://clinicaltrials.gov。
Serum glial fibrillary acid protein associates with TSPO-expressing lesions in multiple sclerosis brain.
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.
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 [11C]PK11195 radioligand.
Results: sGFAP was higher among people with progressive MS (median 122 pg/ml) compared to healthy controls (median 59 pg/ml, p = 0.0002) or participants with relapsing-remitting MS (median 77 pg/ml, p = 0.0056). Among people with MS, higher sGFAP associated with higher volume of chronic lesions with increased TSPO activity (r = 0.36, p = 0.0011) and with thalamic TSPO activity (r = 0.30, p = 0.0069), as well as with T1 and T2 lesion loads (r = 0.38, 0.41, p = 0.0005, 0.0002, respectively). Smaller normal-appearing white matter (r = -0.36, p = 0.0009), cortical gray matter, and thalamus volumes (r = -0.39, p = 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.
期刊介绍：
Therapeutic Advances in Neurological Disorders is a peer-reviewed, open access journal delivering the highest quality articles, reviews, and scholarly comment on pioneering efforts and innovative studies across all areas of neurology. The journal has a strong clinical and pharmacological focus and is aimed at clinicians and researchers in neurology, providing a forum in print and online for publishing the highest quality articles in this area.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
