Comabella Manuel, Río Jordi, Espejo Carmen, Ruiz de Villa Mamen, Al-Zayat Hammad, Nos Carlos, Deisenhammer Florian, Baranzini Sergio E, Nonell Lara, López Cristina, Julià Eva, Oksenberg Jorge R, Montalban Xavier
Unitat de Neuroimmunologia Clínica, CEM-Cat, Hospital Universitari Vall d'Hebron (HUVH), Barcelona, Spain.
Clin Immunol. 2009 Feb;130(2):145-50. doi: 10.1016/j.clim.2008.09.010. Epub 2008 Oct 21.
Matrix metalloproteinases (MMPs) and tissue inhibitors (TIMPs) play a key role in the pathogenesis of multiple sclerosis (MS) and have been proposed as biomarkers of response to therapy. We investigated serum levels of several MMPs and TIMPs in 43 relapsing-remitting MS (RRMS) patients undergoing interferon-beta (IFN-b) treatment and classified as responders and non-responders based on clinical criteria. Levels of MMP-2, MMP-7, MMP-9, TIMP-1 and TIMP-2 were determined by ELISA before treatment and after 3, 6, 12, and 24 months of therapy. Neutralizing antibodies were determined by the myxovirus A induction bioassay. Treatment with IFN-b induced changes in levels of MMP-9 and TIMP-1. In contrast to non-responders, IFN-b resulted in an early and sustained increase in TIMP-1 levels in MS patients who showed clinical response to IFN-b. The early and sustained increase in TIMP-1 levels could be a marker of the response to IFN-b during the first 2 years of treatment.
基质金属蛋白酶（MMPs）和组织抑制剂（TIMPs）在多发性硬化症（MS）的发病机制中起关键作用，并已被提议作为治疗反应的生物标志物。我们调查了43例接受干扰素-β（IFN-β）治疗的复发缓解型MS（RRMS）患者的几种MMPs和TIMPs的血清水平，并根据临床标准将其分为反应者和无反应者。在治疗前以及治疗3、6、12和24个月后，通过酶联免疫吸附测定法（ELISA）测定MMP-2、MMP-7、MMP-9、TIMP-1和TIMP-2的水平。通过黏液病毒A诱导生物测定法测定中和抗体。IFN-β治疗引起了MMP-9和TIMP-1水平的变化。与无反应者相比，IFN-β导致对IFN-β有临床反应的MS患者TIMP-1水平早期且持续升高。TIMP-1水平的早期且持续升高可能是治疗前两年对IFN-β反应的一个标志物。
