De Masi Roberto, Orlando Stefania
Complex Operative Unit of Neurology, "F. Ferrari" Hospital, Casarano, 73042 Lecce, Italy.
Laboratory of Neuroproteomics, Multiple Sclerosis Centre, "F. Ferrari" Hospital, Casarano, 73042 Lecce, Italy.
Pharmaceuticals (Basel). 2021 Nov 21;14(11):1195. doi: 10.3390/ph14111195.
Multiple sclerosis (MS) still lacks reliable biomarkers of neuroinflammation predictive for disease activity and treatment response. Thus, in a prospective study we assessed 55 MS patients (28 interferon (IFN)-treated, 10 treated with no-IFN therapies, 17 untreated) and 20 matched healthy controls (HCs) for the putative correlation of the densitometric expression of glucosidase II alpha subunit (GANAB) with clinical/paraclinical parameters and with interferon-induced protein 35 (IFI35). We also assessed the disease progression in terms of the Rio Score (RS) in order to distinguish the responder patients to IFN therapy (RS = 0) from the non-responder ones (RS ≥ 1). We found GANAB to be 2.51-fold downregulated in the IFN-treated group with respect to the untreated one ( < 0.0001) and 3.39-fold downregulated in responder patients compared to the non-responders ( < 0.0001). GANAB correlated directly with RS (r = 0.8088, < 0.0001) and lesion load (LL) (r = 0.5824, = 0.0014) in the IFN-treated group and inversely with disease duration (DD) (r = -0.6081, = 0.0096) in the untreated one. Lower mean values were expressed for GANAB than IFI35 in IFN responder ( < 0.0001) and higher mean values in the non-responder patients ( = 0.0022). Inverse correlations were also expressed with IFI35 in the overall patient population (r = -0.6468, < 0.0001). In conclusion, the modular expression of GANAB reflects IFI35, RS, DD, and LL values, making it a biomarker of neuroinflammation that is predictive for disease activity and treatment response in MS.
多发性硬化症（MS）仍然缺乏可预测疾病活动和治疗反应的可靠神经炎症生物标志物。因此，在一项前瞻性研究中，我们评估了55例MS患者（28例接受干扰素（IFN）治疗，10例接受非IFN疗法治疗，17例未治疗）和20例匹配的健康对照（HC），以探讨葡糖苷酶IIα亚基（GANAB）的光密度表达与临床/副临床参数以及与干扰素诱导蛋白35（IFI35）之间的假定相关性。我们还根据里约评分（RS）评估了疾病进展情况，以便区分对IFN治疗有反应的患者（RS = 0）和无反应的患者（RS≥1）。我们发现，与未治疗组相比，GANAB在IFN治疗组中下调了2.51倍（<0.0001），与无反应者相比，反应者患者中GANAB下调了3.39倍（<0.0001）。在IFN治疗组中，GANAB与RS（r = 0.8088，<0.0001）和病灶负荷（LL）（r = 0.5824，= 0.0014）直接相关，而在未治疗组中与疾病持续时间（DD）呈负相关（r = -0.6081，= 0.0096）。在IFN反应者中，GANAB的平均值低于IFI35（<0.0001），而在无反应患者中平均值较高（= 0.0022）。在整个患者群体中，GANAB与IFI35也呈负相关（r = -0.6468，<0.0001）。总之，GANAB的模块化表达反映了IFI35、RS、DD和LL值，使其成为一种可预测MS疾病活动和治疗反应的神经炎症生物标志物。
