de Andrés Clara, Aristimuño Carol, Bartolomé Manuel, de Las Heras Virginia, Martínez-Ginés Ma Luisa, Arroyo Rafael, Fernández-Cruz Eduardo, Sánchez-Ramón Silvia
Department of Neurology, Gregorio Marañón University General Hospital, Madrid, Spain.
J Neuroimmunol. 2009 Jul 25;212(1-2):112-20. doi: 10.1016/j.jneuroim.2009.04.009. Epub 2009 May 15.
Many variables with association with better response to interferon-beta-1a (IFNbeta-1a) have been described, but none has yet been shown to be predictive of clinical response. In this real-life observational 1-year longitudinal study of 23 relapsing-remitting multiple sclerosis (RRMS) patients treated with subcutaneous IFNbeta-1a, we have shown a lower proportion of circulating myeloid dendritic cells (mDCs) than in healthy controls at baseline. Both univariate (Kaplan-Meier) and multivariate (Cox regression) analyses were conducted to determine which variables (age, sex, baseline EDSS, MS relapse rates 1 year and 2 years before initiating IFNbeta-1a, mDCs and plasmacytoid (pDCs) subsets, activated and regulatory CD4(+) T-cells (T(Reg))) were associated with clinical response to IFNbeta-1a. During 1 year of treatment, we observed a shift towards lower proportions of CD123(+) pDCs expression and higher numbers and function of the T(Reg). Univariate analysis disclosed that MS activity was significantly associated with baseline BDCA1(+) mDCs below < or = 0.4% (p<0.0025). Cox model analysis revealed that baseline BDCA1(+) mDCs was the most closely associated factor with MS activity on IFN treatment during the 1-year follow-up (p<0.01). A better understanding of the rules that govern the T(Reg)-DC relationship will enable scientists to better manage the immune response in MS patients.
许多与对β-1a干扰素(IFNβ-1a)反应更好相关的变量已被描述,但尚未有任何一个被证明可预测临床反应。在这项对23例接受皮下注射IFNβ-1a治疗的复发缓解型多发性硬化症(RRMS)患者进行的为期1年的真实观察性纵向研究中,我们发现基线时循环髓样树突状细胞(mDCs)的比例低于健康对照组。进行了单变量(Kaplan-Meier)和多变量(Cox回归)分析,以确定哪些变量(年龄、性别、基线扩展残疾状态量表(EDSS)、开始使用IFNβ-1a前1年和2年的MS复发率、mDCs和浆细胞样(pDCs)亚群、活化和调节性CD4(+) T细胞(T(Reg)))与对IFNβ-1a的临床反应相关。在1年的治疗期间,我们观察到CD123(+) pDCs表达比例降低,T(Reg)数量和功能增加。单变量分析显示,MS活动与基线BDCA1(+) mDCs低于或等于0.4%显著相关(p<0.0025)。Cox模型分析显示,在1年随访期间,基线BDCA1(+) mDCs是与IFN治疗期间MS活动最密切相关的因素(p<0.01)。更好地理解控制T(Reg)-DC关系的规则将使科学家能够更好地管理MS患者的免疫反应。