Santos Roseane, Weinstock-Guttman Bianca, Tamaño-Blanco Miriam, Badgett Darlene, Zivadinov Robert, Justinger Theresa, Munschauer Frederick, Ramanathan Murali
Department of Pharmaceutical Sciences, State University of New York at Buffalo, and Jacobs Neurological Institute, Buffalo General Hospital, NY 14260-1200, United States.
J Neuroimmunol. 2006 Jul;176(1-2):125-33. doi: 10.1016/j.jneuroim.2006.03.019. Epub 2006 May 15.
The objective of this study was to evaluate multiple interferon (IFN) specific mRNA biomarkers in multiple sclerosis (MS) patients with anti-IFN-beta neutralizing antibodies (NAB) using a pharmacodynamic study design. Thirty patients were enrolled. Blood samples were drawn at pre-treatment, 4-, 8-h time points following the intramuscular dose of IFN-beta-1a. Total RNA was obtained from peripheral blood cells, processed to cDNA and analyzed using quantitative real-time polymerase chain reaction. Pre-treatment serum samples were analyzed for anti-IFN-beta binding and neutralizing antibodies: 22 patients were NAB negative; equal numbers of the eight remaining patients were either NAB positive or had borderline NAB status. The results showed that early assessment (at 4 h after IFN-beta injection) of mRNAs for Stat-1, MxA, MxB and TRAIL was more sensitive than the later measurements. Furthermore, the NAB positive patients had strongly attenuated gene expression responses on all the mRNAs. Patients with borderline NAB had average responses that appear to be lower than NAB negative patients on several genes, notably Stat-1, TRAIL and beta2 microglobulin.
本研究的目的是采用药效学研究设计，评估患有抗干扰素-β中和抗体（NAB）的多发性硬化症（MS）患者体内的多种干扰素（IFN）特异性mRNA生物标志物。招募了30名患者。在肌肉注射干扰素-β-1a前、注射后4小时和8小时的时间点采集血样。从外周血细胞中获取总RNA，加工成cDNA，并使用定量实时聚合酶链反应进行分析。对治疗前血清样本进行抗干扰素-β结合和中和抗体分析：22名患者NAB阴性；其余8名患者中，NAB阳性和临界NAB状态的患者数量相等。结果表明，对Stat-1、Mx A、Mx B和TRAIL的mRNA进行早期评估（在注射干扰素-β后4小时）比后期测量更敏感。此外，NAB阳性患者对所有mRNA的基因表达反应均显著减弱。临界NAB患者的平均反应在几个基因上似乎低于NAB阴性患者，特别是Stat-1、TRAIL和β2微球蛋白。
