Granulocyte activation markers in cerebrospinal fluid differentiate acute neuromyelitis spectrum disorder from multiple sclerosis.
Granulocyte activation markers in cerebrospinal fluid differentiate acute neuromyelitis spectrum disorder from multiple sclerosis.
复制标题
DOI：
10.1136/jnnp-2022-330796
复制
发表时间：
2023-09
期刊：
影响因子：
--
通讯作者：
中科院分区：
文献类型：
--
作者：
粒细胞侵入大脑是区别视神经脊髓炎谱系障碍(NMOSD)和多发性硬化症(MS)的病理解剖特征。我们的目的是确定脑脊液中的粒细胞激活标志物(GAM)是否可以作为区分NMOSD和MS的生物标志物，以及水平是否与神经功能损害有关。我们定量检测了两组混合型NMOSD和复发性多发性硬化症(RRMS)患者脑脊液中5种GAM(中性粒细胞弹性蛋白酶、髓过氧化物酶、中性粒细胞明胶酶相关脂蛋白、基质金属蛋白酶-8、金属蛋白酶组织抑制因子-1)的水平，以及一组已知在NMOSD和MS(神经丝轻链、胶质纤维酸性蛋白、S100B、基质金属蛋白酶-9、细胞间黏附分子-1、血管细胞黏附分子-1)中上调的炎症和组织破坏标志物。在急性NMOSD患者中，GAM和黏附分子高于RRMS，而其他指标均高于RRMS，并与实际的临床残疾评分相关。GAM峰值出现在NMOSD发作时，而MS时GAM水平稳定较低，这使得≤从临床恶化开始21天起就可以区分这两种疾病。GAM组合提供了0.90-0.98(特异度0.76-1.0，灵敏度0.87-1.0)曲线下面积来区分NMOSD和MS，包括所有未经治疗的抗水通道蛋白4(AAQP4)抗体阴性患者。GAM复合体是一种新的生物标志物，可以可靠地区分NMOSD和MS，包括在AQP4−NMOSD中。GAM与并发神经损害程度的相关性为它们的致病作用提供了证据，进而表明它们是急性NMOSD的潜在药物靶点。
Granulocyte invasion into the brain is a pathoanatomical feature differentiating neuromyelitis optica spectrum disorder (NMOSD) from multiple sclerosis (MS). We aimed to determine whether granulocyte activation markers (GAM) in cerebrospinal fluid (CSF) can be used as a biomarker to distinguish NMOSD from MS, and whether levels associate with neurological impairment. We quantified CSF levels of five GAM (neutrophil elastase, myeloperoxidase, neutrophil gelatinase-associated lipocalin, matrixmetalloproteinase-8, tissue inhibitor of metalloproteinase-1), as well as a set of inflammatory and tissue-destruction markers, known to be upregulated in NMOSD and MS (neurofilament light chain, glial fibrillary acidic protein, S100B, matrix metalloproteinase-9, intercellular adhesion molecule-1, vascular cellular adhesion molecule-1), in two cohorts of patients with mixed NMOSD and relapsing-remitting multiple sclerosis (RRMS). In acute NMOSD, GAM and adhesion molecules, but not the other markers, were higher than in RRMS and correlated with actual clinical disability scores. Peak GAM levels occurred at the onset of NMOSD attacks, while they were stably low in MS, allowing to differentiate the two diseases for ≤21 days from onset of clinical exacerbation. Composites of GAM provided area under the curve values of 0.90–0.98 (specificity of 0.76–1.0, sensitivity of 0.87–1.0) to differentiate NMOSD from MS, including all anti-aquaporin-4 protein (aAQP4)-antibody-negative patients who were untreated. GAM composites represent a novel biomarker to reliably differentiate NMOSD from MS, including in aAQP4− NMOSD. The association of GAM with the degree of concurrent neurological impairment provides evidence for their pathogenic role, in turn suggesting them as potential drug targets in acute NMOSD.
登录
查看更多内容
DOI：
10.1212/nxi.0000000000001149
发表时间：
2022-05
期刊：
Neurology(R) neuroimmunology & neuroinflammation
影响因子：
--
作者：
Murata H;Kinoshita M;Yasumizu Y;Motooka D;Beppu S;Shiraishi N;Sugiyama Y;Kihara K;Tada S;Koda T;Konaka H;Takamatsu H;Kumanogoh A;Okuno T;Mochizuki H
通讯作者：
Mochizuki H
影响因子：
2.6
作者：
Benoit SW;Fukuda T;VandenHeuvel K;Witte D;Fuller C;Willis J;Dixon BP;Drake KA
通讯作者：
Drake KA
DOI：
10.1111/bpa.12099
发表时间：
2014-01
期刊：
Brain pathology (Zurich, Switzerland)
影响因子：
--
作者：
Lucchinetti CF;Guo Y;Popescu BF;Fujihara K;Itoyama Y;Misu T
通讯作者：
Misu T
影响因子：
3.4
作者：
Hochmeister, Sonja;Gattringer, Thomas;Hoeftberger, Romana
通讯作者：
Hoeftberger, Romana
影响因子：
11
作者：
Bonnan, Mickael;Valentino, Rudy;Cabre, Philippe
通讯作者：
Cabre, Philippe