Gilli F, Marnetto F, Caldano M, Sala A, Malucchi S, Capobianco M, Bertolotto A
Centro di Riferimento Regionale Sclerosi Multipla (CReSM) & Neurobiologia Clinica, ASO S. Luigi Gonzaga, Orbassano, Torino, Italy.
Mult Scler. 2006 Feb;12(1):47-57. doi: 10.1191/135248506ms1245oa.
Biological activity of interferon-beta (IFNbeta) can be assessed by measuring IFN-stimulated genes (ISGs). Among them, myxovirus resistance protein A (MxA) appears to have the highest specificity, but it has no role in the pathogenesis of multiple sclerosis (MS). To investigate the reliability of MxA as a biomarker, we compared its expression to that of two other ISGs: TNF-related apoptosis-inducing ligand (TRAIL) and X-linked inhibitor of apoptosis factor-1 (XAF-1). Both were shown to be involved in immunoregulatory mechanisms and might play a role in MS. Quantitative-PCR measurements were performed in peripheral blood mononuclear cells from 73 MS patients after short-term and long-term treatment with IFNbeta. A time-dependent response for multiple ISGs was observed in all patients after short-term treatment. In contrast, long-term treatment induced concurrent inhibition of ISGs in 12.3% (9/73) of patients, in whom neutralizing antibodies (NAbs) were detectable. Besides, 22% (16/73) of chronically treated patients showed a non-NAbs-related abrogation of TRAIL expression. In summary, 1) MxA expression was significantly higher than both TRAIL and XAF-1, and 2) MxA was the most sensitive gene to detect decreased bioavailability due to NAbs. These findings identify MxA as an appropriate biomarker for IFNbeta, although there is no evidence for a functional role of it in MS.
β干扰素（IFNβ）的生物活性可通过检测干扰素刺激基因（ISG）来评估。其中，黏液病毒抗性蛋白A（MxA）似乎具有最高的特异性，但它在多发性硬化症（MS）的发病机制中不起作用。为了研究MxA作为生物标志物的可靠性，我们将其表达与另外两种ISG的表达进行了比较：肿瘤坏死因子相关凋亡诱导配体（TRAIL）和X连锁凋亡抑制因子-1（XAF-1）。这两种蛋白均被证明参与免疫调节机制，可能在MS中发挥作用。对73例MS患者外周血单个核细胞进行定量PCR检测，这些患者接受了短期和长期的IFNβ治疗。短期治疗后，所有患者均观察到多种ISG的时间依赖性反应。相比之下，长期治疗导致12.3%（9/73）的患者出现ISG同时受到抑制，这些患者可检测到中和抗体（NAb）。此外，22%（16/73）接受长期治疗的患者显示出与NAb无关的TRAIL表达缺失。总之，1）MxA的表达显著高于TRAIL和XAF-1，2）MxA是检测由于NAb导致生物利用度降低最敏感的基因。这些发现确定MxA是IFNβ的合适生物标志物，尽管没有证据表明它在MS中具有功能作用。
