Department of Neurology, Geisel School of Medicine & Dartmouth-Hitchcock Medical Center, One Medical Center Drive, Lebanon, NH, 03756, USA.
Fluids Barriers CNS. 2021 Feb 25;18(1):9. doi: 10.1186/s12987-021-00244-5.
Pilz et al. (Fluids Barriers CNS 17:7; 2020) investigated how CSF CXCL13 concentrations are influenced by CXCL13 serum concentrations and blood-CSF barrier (BCSFB) function, comparing the impact of serum CXCL13 levels and Q (CSF albumin/serum albumin) on CSF CXCL13 among patients with CNS inflammation categorized as CXCL13 negative, low, medium, or high. Among all CXCL13 groups, their results showed no correlation between CSF CXCL13 concentrations and serum CXCL13 or Q. The authors argue that, in contrast to other proteins, CXCL13 passage across the BCSFB does not occur, regardless of BCSFB function, and is instead solely influenced by intrathecal production. In contrast to the authors' findings, in our studies including both non-inflammatory neurological disorders (NIND; n = 62) and multiple sclerosis (MS) patients we observed a significant correlation between serum CXCL13 concentrations and CSF CXCL13 concentrations. We review several observations which may underlie these contrasting results, including (1) the impact of serum CXCL13 concentrations on CSF CXCL13 in patients with lower intrathecal CXCL13 production and thus lower CXCL13 concentrations (i.e. NIND and MS), (2) the proposed diffusion dynamics of the small molecule CXCL13 across the BCSFB, and (3) differing definitions of negative versus elevated CSF CXCL13 concentrations determined by an assay's relative sensitivity. In conclusion, we argue that for patients with moderately elevated CSF CXCL13 concentrations, serum CXCL13 concentrations influence CSF CXCL13 levels, and thus the appropriate corrections including incorporation of CSF/serum ratios and Q values should be utilized.
皮耳兹等人（Fluids Barriers CNS 17:7; 2020）研究了 CSF CXCL13 浓度如何受到 CXCL13 血清浓度和血脑屏障（BCSFB）功能的影响，比较了血清 CXCL13 水平和 Q（CSF 白蛋白/血清白蛋白）对 CXCL13 阴性、低、中或高的中枢神经系统炎症患者 CSF CXCL13 的影响。在所有 CXCL13 组中，他们的结果表明 CSF CXCL13 浓度与血清 CXCL13 或 Q 之间没有相关性。作者认为，与其他蛋白质不同，CXCL13 穿过 BCSFB 的情况不会发生，无论 BCSFB 功能如何，而仅仅受到鞘内产生的影响。与作者的发现相反，在我们包括非炎症性神经疾病（NIND；n=62）和多发性硬化症（MS）患者在内的研究中，我们观察到血清 CXCL13 浓度与 CSF CXCL13 浓度之间存在显著相关性。我们回顾了几个可能导致这些对比结果的观察结果，包括：（1）血清 CXCL13 浓度对 CSF CXCL13 的影响，在鞘内 CXCL13 产生较低且因此 CXCL13 浓度较低的患者中（即 NIND 和 MS）；（2）小分子 CXCL13 穿过 BCSFB 的扩散动力学；（3）通过测定法的相对敏感性确定的 CSF CXCL13 浓度的阴性与升高的不同定义。总之，我们认为对于 CSF CXCL13 浓度中度升高的患者，血清 CXCL13 浓度会影响 CSF CXCL13 水平，因此应适当进行校正，包括纳入 CSF/血清比值和 Q 值。
