Fainardi Enrico, Rizzo Roberta, Melchiorri Loredana, Castellazzi Massimiliano, Govoni Vittorio, Caniatti Luisa, Paolino Ezio, Tola Maria Rosaria, Granieri Enrico, Baricordi Olavio Roberto
Multiple Sclerosis Center, Department of Neurology, University of Ferrara, Arcispedale S. Anna, Corso della Giovecca 203, Ferrara I-44100, Italy.
J Neuroimmunol. 2004 Mar;148(1-2):206-11. doi: 10.1016/j.jneuroim.2003.12.002.
It has recently become clear that interferon-beta (IFN-beta) treatment is effective in ameliorating relapsing-remitting multiple sclerosis (RRMS) through an as yet unidentified mechanism. As there is no recognisable biological indicator to predict responsiveness to IFN-beta treatment, we have investigated fluctuations in serum sHLA-I levels in MS patients undergoing IFN-beta 1b therapy. Serum sHLA-I concentrations measured by enzyme-linked immunosorbent assay (ELISA) were assessed at baseline and, longitudinally, over a period of 18 months after the start of treatment in 29 RRMS patients grouped as responders and nonresponders according to their clinical response to IFN-beta 1b therapy. Thirty-nine healthy volunteers served as controls. Serum sHLA-I concentrations were significantly higher (p<0.001) in pretreated RRMS patients than in healthy donors. In MS patients, changes in mean serum levels of sHLA-I from baseline showed a temporal pattern characterized by a strong increase in the first trimester of treatment, a return toward basal values in the following 6 months, a slight decline at 12th and 15th months and a further moderate increase at the 18th month. Mean serum sHLA-I levels were significantly more elevated in responders than in nonresponders at the first (p<0.02), second (p<0.01), and at third (p<0.02) months after the beginning of treatment and significantly lower (p<0.01) at the time of relapses in comparison to baseline values. Overall, these results seem to indicate that IFN-beta 1b can modulate fluctuations in serum sHLA-I levels and argue in favour of a potential role for serum levels of sHLA-I as a sensitive marker to monitor response to IFN-beta treatment in MS.
最近已明确,β-干扰素(IFN-β)治疗可通过一种尚未明确的机制有效改善复发缓解型多发性硬化症(RRMS)。由于尚无可识别的生物学指标来预测对IFN-β治疗的反应性,我们研究了接受IFN-β 1b治疗的MS患者血清可溶性人类白细胞抗原I类分子(sHLA-I)水平的波动情况。通过酶联免疫吸附测定(ELISA)测量血清sHLA-I浓度,在基线时进行评估,并在29例RRMS患者开始治疗后的18个月内进行纵向评估,这些患者根据其对IFN-β 1b治疗的临床反应分为反应者和无反应者。39名健康志愿者作为对照。预处理的RRMS患者血清sHLA-I浓度显著高于健康供体(p<0.001)。在MS患者中,sHLA-I的平均血清水平相对于基线的变化呈现出一种时间模式,其特征为治疗的前三个月大幅升高,随后6个月恢复至基础值,在第12个月和第15个月略有下降,在第18个月进一步适度升高。治疗开始后的第一个月(p<0.02)、第二个月(p<0.01)和第三个月(p<0.02),反应者的平均血清sHLA-I水平显著高于无反应者,与基线值相比,复发时显著降低(p<0.01)。总体而言,这些结果似乎表明IFN-β 1b可调节血清sHLA-I水平的波动,并支持血清sHLA-I水平作为监测MS患者对IFN-β治疗反应的敏感标志物的潜在作用。