Department of Neurology, Baird MS center, Jacobs Neurological Institute, 100 High St, Buffalo, NY 14203, USA.
J Neuroinflammation. 2010 Oct 29;7:72. doi: 10.1186/1742-2094-7-72.
This study compared the level of advanced glycation end products (AGEs), N-(Carboxymethyl)lysine (CML) and N-(Carboxyethyl)lysine (CEL), in patients with multiple sclerosis (MS) and healthy controls (HCs), correlating these markers with clinical indicators of MS disease severity.
CML and CEL plasma levels were analyzed in 99 MS patients and 43 HCs by tandem mass spectrometry (LC/MS/MS). Patients were stratified based on drug modifying therapies (DMTs) including interferon beta, glatiramer acetate and natalizumab.
The level of plasma CEL, but not CML, was significantly higher in DMT-naïve MS patients when compared to HCs (P < 0.001). Among MS patients, 91% had higher than mean plasma CEL observed in HCs. DMTs reduced CML and CEL plasma levels by approximately 13% and 40% respectively. CML and CEL plasma levels correlated with the rate of MS clinical relapse.
Our results suggest that AGEs in general and CEL in particular could be useful biomarkers in MS clinical practice. Longitudinal studies are warranted to determine any causal relationship between changes in plasma level of AGEs and MS disease pathology. These studies will pave the way for use of AGE inhibitors and AGE-breaking agents as new therapeutic modalities in MS.
本研究比较了多发性硬化症(MS)患者和健康对照者(HCs)中晚期糖基化终产物(AGEs)、N-(羧甲基)赖氨酸(CML)和 N-(羧乙基)赖氨酸(CEL)的水平,并将这些标志物与 MS 疾病严重程度的临床指标相关联。
通过串联质谱(LC/MS/MS)分析了 99 名 MS 患者和 43 名 HCs 的 CML 和 CEL 血浆水平。根据药物修饰疗法(DMTs)对患者进行分层,包括干扰素β、那他珠单抗和格拉替雷。
与 HCs 相比,DMT 初治 MS 患者的血浆 CEL 水平显著升高(P<0.001),但 CML 水平无显著差异。在 MS 患者中,91%的患者的血浆 CEL 水平高于 HCs 的平均值。DMTs 可使 CML 和 CEL 血浆水平分别降低约 13%和 40%。CML 和 CEL 血浆水平与 MS 临床复发率相关。
我们的结果表明,AGEs 一般和 CEL 特别可能是 MS 临床实践中的有用生物标志物。需要进行纵向研究以确定 AGE 血浆水平变化与 MS 疾病病理之间的任何因果关系。这些研究将为 AGE 抑制剂和 AGE 断裂剂作为 MS 的新治疗方式铺平道路。