National Pediatric Myoclonus Center and Neuroimmunology Research Laboratory, P.O. Box 19643, Springfield, IL 62794-9643, USA; Department of Neurology, SouthernIllinois University School of Medicine, P.O. Box 19643, Springfield, IL 62794-9643, USA.
Cytokine. 2013 Oct;64(1):331-6. doi: 10.1016/j.cyto.2013.05.020. Epub 2013 Jun 10.
Identifying and blocking chemokine inflammatory mediators in pediatric opsoclonus-myoclonus syndrome (OMS) is critical to the treatment of this autoimmune, paraneoplastic, neurological disorder. In a prospective, case-control, clinico-scientific study of children with OMS compared to non-inflammatory neurological controls and other inflammatory neurological disorders, CCL19 (n=369) and CCL21 (n=312) were quantified in CSF and serum, respectively, by ELISA. Both cross-sectional and longitudinal effects of OMS and various immunotherapies were evaluated. Significant upregulation of CCL21 concentration (mean ± SD) (+32%) was found in serum of untreated OMS (630 ± 133 pg/mL), compared to controls (478 ± 168 pg/mL), (p<0.0001). Both corticosteroids and ACTH (corticotropin) significantly lowered CCL21 to control levels, as they did in combination with IVIg, rituximab, cyclophosphamide or other treatments, without additional reduction attributable to the other agents. In a pilot longitudinal study of ACTH-based triple therapy, the mean serum CCL21 concentration fell 59% from elevated to less than 1 SD below controls 1 week after high-dose ACTH, gradually returning to the control mean with ACTH tapering by 3 weeks and out to 12 weeks (p<0.0001). In contrast, CCL19, detectable in CSF, was not significantly altered by OMS or various immunotherapies. In the "high" CCL21 subgroup, higher serum concentrations of CCL22 (+57%) and CXCL13 (+40%), as well as the CSF concentration of BAFF (+64%), also were found. Elevated serum CCL21, not CSF CCL19, correlates with OMS severity and duration in pediatric OMS. Corticosteroids and ACTH were the only immunotherapies evaluated that down-regulated CCL21 production. Validation studies are needed to assess treatment biomarker status.
鉴定和阻断趋化因子炎症介质在儿科发作性眼球运动性震颤-肌阵挛综合征（OMS）的治疗中至关重要，因为这种疾病是自身免疫性、副肿瘤性、神经退行性疾病。在一项前瞻性、病例对照、临床科学研究中，对 OMS 患儿与非炎症性神经系统对照组和其他炎症性神经系统疾病患儿进行比较，通过 ELISA 分别对脑脊液和血清中的 CCL19（n=369）和 CCL21（n=312）进行定量分析。评估了 OMS 和各种免疫疗法的横断面和纵向效应。未治疗的 OMS 患儿血清中 CCL21 浓度（平均值±标准差）（+32%）显著升高（630±133pg/mL），与对照组相比（478±168pg/mL）（p<0.0001）。皮质类固醇和 ACTH（促皮质素）均显著降低 CCL21 至对照水平，与 IVIg、利妥昔单抗、环磷酰胺或其他治疗联合使用时也是如此，并且没有因其他药物而额外降低。在一项基于 ACTH 的三联疗法的试点纵向研究中，ACTH 高剂量治疗后 1 周，血清 CCL21 浓度从升高水平下降 59%，低于对照组 1 个标准差以下，随着 ACTH 逐渐减少，3 周时恢复到对照组平均值，到 12 周时恢复（p<0.0001）。相比之下，OMS 或各种免疫疗法并未显著改变可检测到 CSF 的 CCL19。在“高”CCL21 亚组中，还发现血清 CCL22（+57%）和 CXCL13（+40%）浓度升高，以及 BAFF（+64%）的 CSF 浓度升高。在儿科 OMS 中，血清 CCL21 升高而 CSF CCL19 不变与 OMS 严重程度和持续时间相关。皮质类固醇和 ACTH 是评估的唯一可下调 CCL21 产生的免疫疗法。需要进行验证研究以评估治疗生物标志物状态。
