Department of Pediatric Neurology, Medical Faculty, Gazi University, Ankara, Turkey.
Pediatr Neurol. 2012 Sep;47(3):171-6. doi: 10.1016/j.pediatrneurol.2012.05.027.
Matrix metalloproteinases and their tissue inhibitors play a key role in the pathogenesis of adult-onset multiple sclerosis, and were suggested as biomarkers of response to interferon-β, an established treatment in multiple sclerosis. However, data regarding pediatric population are scarce. We determined serum levels of matrix metalloproteinase-7, matrix metalloproteinase-9, and tissue inhibitor of matrix metalloproteinase-1 in children, and evaluated effects of interferon-β therapy on these measures. Serum samples from 14 children with relapsing, remitting multiple sclerosis at baseline and at month 12, and from 15 controls, were collected. Interferon-β treatment was initiated in eight patients. Mean serum matrix metalloproteinase-9 levels and matrix metalloproteinase-9/tissue inhibitor of matrix metalloproteinase-1 ratio were higher in patients compared with controls, and were reduced significantly in treated patients at month 12, but did not change in untreated patients. Mean matrix metalloproteinase-7 levels were lower in patients compared with controls, and increased significantly in the treated group, but did not change significantly in the untreated group. In pediatric multiple sclerosis, a shift in matrix metalloproteinase-9/tissue inhibitor of matrix metalloproteinase-1 balance toward proteolytic activity is evident, and interferon-β therapy demonstrates a beneficial effect on this disturbed balance.
基质金属蛋白酶及其组织抑制剂在成人发病的多发性硬化症的发病机制中起关键作用，并且被认为是干扰素-β反应的生物标志物，干扰素-β是多发性硬化症的一种既定治疗方法。然而，关于儿科人群的数据却很少。我们测定了儿童血清中基质金属蛋白酶-7、基质金属蛋白酶-9 和基质金属蛋白酶组织抑制剂-1 的水平，并评估了干扰素-β治疗对这些指标的影响。在基线和 12 个月时，采集了 14 例复发缓解型多发性硬化症患儿和 15 例对照者的血清样本。8 例患儿开始接受干扰素-β治疗。与对照组相比，患者的基质金属蛋白酶-9 水平和基质金属蛋白酶-9/基质金属蛋白酶组织抑制剂-1 比值均较高，在治疗 12 个月时显著降低，但未接受治疗的患者则无变化。与对照组相比，患者的基质金属蛋白酶-7 水平较低，且在治疗组中显著升高，但在未接受治疗的患者中无明显变化。在儿科多发性硬化症中，基质金属蛋白酶-9/基质金属蛋白酶组织抑制剂-1 平衡向蛋白水解活性转变明显，而干扰素-β治疗对这种失衡具有有益的影响。
