Fernández-Espejo Emilio, Rodríguez de Fonseca Fernando, Gavito Ana Luisa, Córdoba-Fernández Antonio, Chacón José, Martín de Pablos Ángel
Reial Acadèmia de Medicina de Catalunya, 08001 Barcelona, Spain.
Laboratorio de Medicina Regenerativa, Hospital Regional Universitario, 29010 Málaga, Spain.
Antioxidants (Basel). 2022 May 30;11(6):1088. doi: 10.3390/antiox11061088.
Background: Myeloperoxidase (MPO) and advanced oxidation protein products, or AOPP (a type of MPO-derived chlorinated adducts), have been implicated in Parkinson´s disease (PD). Human MPO also show sex-based differences in PD. The objective was to study the relationship of MPO and AOPP in the cerebrospinal fluid (CSF) with motor features of idiopathic PD in male and female patients. Methods: MPO concentration and activity and AOPP content were measured in the CSF and serum in 34 patients and 30 controls. CSF leukocytes and the integrity of the blood-brain barrier were evaluated. Correlations of MPO and AOPP with clinical variables were examined. Results: The blood-brain barrier was intact and CSF leukocyte count was normal in all patients. CSF MPO concentration and activity were similar in the cohort of patients and controls, but CSF MPO content was significantly higher in male patients than in PD women (p = 0.0084). CSF MPO concentration correlated with disease duration in male and female patients (p < 0.01). CSF MPO concentration was significantly higher in men with disease duration ≥12 years versus the remainder of the male subjects (p < 0.01). Changes in CSF MPO in women were not significant. Serum MPO concentration and activity were significantly higher in all PD patients relative to controls (p < 0.0001). CSF MPO was not correlated with serum MPO. Serum AOPP were detected in all patients, but CSF AOPP was undetectable in 53% of patients. AOPP were not quantifiable in controls. Conclusions: CSF MPO is not a good biomarker for PD because mean CSF MPO concentration and activity are not different between the cohort of patients and controls. CSF MPO concentration positively correlated with disease duration in men and women, but CSF MPO is significantly enhanced only in male patients with disease duration longer than 12 years. It can be hypothesized that the MPO-related immune response in early-stage PD might be weak in all patients, but then the MPO-related immune response is progressively enhanced in men, not women. Since the blood-brain barrier is intact, and CSF MPO is not correlated with serum MPO, CSF myeloperoxidase would reflect MPO content in brain cells, not blood-derived cells. Finally, serum AOPP was detected in all patients, but not controls, which is consistent with the occurrence of chlorinative stress in blood serum in PD. The study of CSF AOPP as biomarker could not be assessed because the ELISA assay was hampered by its detection limit in the CSF.
髓过氧化物酶（MPO）和晚期氧化蛋白产物，即AOPP（一种源自MPO的氯化加合物），与帕金森病（PD）有关。人MPO在PD中也存在基于性别的差异。目的是研究脑脊液（CSF）中MPO和AOPP与男性和女性特发性PD运动特征的关系。方法：测量34例患者和30例对照的CSF和血清中的MPO浓度、活性以及AOPP含量。评估CSF白细胞和血脑屏障的完整性。检查MPO和AOPP与临床变量的相关性。结果：所有患者的血脑屏障均完整，CSF白细胞计数正常。患者组和对照组的CSF MPO浓度和活性相似，但男性患者的CSF MPO含量显著高于PD女性患者（p = 0.0084）。CSF MPO浓度与男性和女性患者的病程相关（p < 0.01）。病程≥12年的男性患者的CSF MPO浓度显著高于其余男性受试者（p < 0.01）。女性患者CSF MPO的变化不显著。所有PD患者的血清MPO浓度和活性均显著高于对照组（p < 0.0001）。CSF MPO与血清MPO不相关。所有患者均检测到血清AOPP，但53%的患者未检测到CSF AOPP。对照组中AOPP无法定量。结论：CSF MPO不是PD的良好生物标志物，因为患者组和对照组之间的平均CSF MPO浓度和活性没有差异。CSF MPO浓度与男性和女性的病程呈正相关，但仅病程超过12年的男性患者的CSF MPO显著升高。可以推测，早期PD中MPO相关的免疫反应在所有患者中可能较弱，但随后男性而非女性的MPO相关免疫反应逐渐增强。由于血脑屏障完整，且CSF MPO与血清MPO不相关，CSF髓过氧化物酶反映的是脑细胞而非血源性细胞中的MPO含量。最后，所有患者均检测到血清AOPP，而对照组未检测到，这与PD患者血清中发生氯化应激一致。由于ELISA检测法在CSF中的检测限限制，无法评估CSF AOPP作为生物标志物的研究。
