CEDOC, Departamento de Bioquímica, Faculdade de Ciências Médicas, Universidade Nova de Lisboa, Lisbon, Portugal.
J Neurol. 2010 Oct;257(10):1703-7. doi: 10.1007/s00415-010-5606-4. Epub 2010 Jun 4.
Interferon-beta (IFN-beta) therapy for multiple sclerosis (MS) is associated with a potential for induction of neutralizing antibodies (NAbs). Because immune reactivity depends on changes in lipoprotein metabolism, we investigated whether plasma lipoprotein profiles could be associated with the development of NAbs. Thirty-one female MS patients treated with subcutaneously administered IFN-beta were included. Demographic and clinical characteristics were compared between NAbs response groups using t tests for continuous and logistic regression analysis and Fisher's exact tests for categorical data, respectively. Multivariate logistic regression was used to evaluate the effect of potential confounders. Patients who developed NAbs had lower apoE levels before treatment, 67 (47-74) mg/L median (interquartile range), and at the moment of NAb analysis, 53 (50-84) mg/L, in comparison to those who remained NAb-negative, 83 (68-107) mg/L, P = 0.03, and 76 (66-87) mg/L, P = 0.04, respectively. When adjusting for age and smoking for a one-standard deviation decrease in apoE levels, a 5.6-fold increase in the odds of becoming NAb-positive was detected: odds ratios (OR) 0.18 (95% CI 0.04-0.77), P = 0.04. When adjusting for apoE, smoking habit became associated with NAb induction: OR 5.6 (95% CI 1.3-87), P = 0.03. These results suggest that apoE-containing lipoprotein metabolism and, possibly, tobacco smoking may be associated with risk of NAb production in female MS patients treated with IFN-beta.
干扰素-β（IFN-β）治疗多发性硬化症（MS）与产生中和抗体（NAb）的潜力有关。由于免疫反应取决于脂蛋白代谢的变化，我们研究了血浆脂蛋白谱是否与 NAb 的产生相关。纳入了 31 名接受皮下注射 IFN-β治疗的女性 MS 患者。使用 t 检验对连续数据和逻辑回归分析对分类数据分别比较 NAb 反应组的人口统计学和临床特征。使用多元逻辑回归评估潜在混杂因素的影响。与未发生 NAb 的患者相比，发生 NAb 的患者在治疗前的载脂蛋白 E（apoE）水平较低，分别为 67（47-74）mg/L 中位数（四分位距）和 NAb 分析时的 53（50-84）mg/L，P = 0.03；和 76（66-87）mg/L，P = 0.04。当根据年龄和吸烟情况对 apoE 水平进行一个标准差的调整时，发生 NAb 阳性的几率增加了 5.6 倍：比值比（OR）为 0.18（95%可信区间 0.04-0.77），P = 0.04。当根据 apoE 进行调整时，吸烟习惯与 NAb 诱导相关：OR 为 5.6（95%可信区间 1.3-87），P = 0.03。这些结果表明，apoE 载脂蛋白代谢，可能还有吸烟，与接受 IFN-β治疗的女性 MS 患者产生 NAb 的风险相关。
