Objective

To comprehensively assess whether neopterin in urine could be a candidate biomarker for determining the neuroinflammatory status in ALS.

Methods

We performed an observational, cross-sectional study in 81 pALS, 68 age- and sex-comparable healthy controls (HC), 14 patients affected by MS and 24 OND patients. ALS patients underwent a neurological evaluation to assess the global functional status evaluated by Amyotrophic Lateral Sclerosis Functional Rating Scale—Revised (ALSFRS-R) and the disease progression rate. Urinary neopterin concentrations were determined by high-performance liquid chromatography method and were recorded at the time of first examination to assess their effect on disease severity and survival.

Results

Urinary neopterin was significantly higher in pALS (263.90 [198.71–474.90]) compared to MS (155.28 [131.74–190.38], p = < .001), OND patients (205.60 [158.96–299.41], p = 0.04) and HC (169.55 [134.91–226.10], p < .001). Moreover, a significant negative correlation was found between neopterin level and the severity of symptoms evaluated by ALSFRS-R total score (r = − 0.46, p < .001) and its subscores (bulbar r = − 0.34, p = 0.002; motor r = − 0.33, p = 0.003; respiratory r = − 0.53, p < .001), also adjusting for the effect of sex, site of onset, age at evaluation and time from onset to evaluation.

Conclusions

Our finding indicates that urine neopterin is elevated in ALS, emphasizing the role of the cell-mediated inflammation in the disease. Moreover, whether confirmed in further studies, our results will underline the neopterin’s potential use as non-invasive clinical biomarker of ALS, to discriminate patients possibly candidates to clinical interventions aimed to interfere the neuroinflammatory processes.

中文翻译：

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尿新蝶呤，肌萎缩性侧索硬化症中神经炎症状态的新标记。

目的

为了全面评估尿液中的新蝶呤是否可以作为确定ALS中神经炎症状态的候选生物标记。

方法

我们对81例pALS，68例年龄和性别可比的健康对照（HC），14例受MS影响的患者和24例OND患者进行了观察性横断面研究。ALS患者接受了神经系统评估，以评估通过修订的肌萎缩性侧索硬化功能评定量表（ALSFRS-R）评估的总体功能状态和疾病进展率。尿新蝶呤浓度通过高效液相色谱法测定，并在首次检查时记录，以评估其对疾病严重程度和生存率的影响。

结果

与MS（155.28 [131.74–190.38]，p  = <.001），OND患者（205.60 [158.96-299.41]，p  = 0.04）和HC（HC）（pALS）（263.90 [198.71–474.90]）相比，尿新蝶呤显着更高。169.55 [134.91–226.10]，p  <.001）。此外，显著呈负相关新蝶呤水平和通过ALSFRS-R总分（评价症状的严重程度之间ř  = - 0.46，p  <0.001）和它的子得分（延髓- [R  = - 0.34，p  = 0.002;马达ř  = − 0.33，p  = 0.003;呼吸r  = − 0.53，p <.001），还调整了性别，发病部位，评估时的年龄以及从评估到评估的时间的影响。

结论

我们的发现表明，尿新蝶呤在ALS中升高，强调了细胞介导的炎症在疾病中的作用。此外，无论是否在进一步的研究中得到证实，我们的结果都将强调新蝶呤作为ALS的非侵入性临床生物标志物的潜在用途，以区分可能干扰神经炎性过程的临床干预措施的患者。