Dept. of Geriatrics, Evangelisches Krankenhaus Göttingen-Weende, Göttingen, Germany; Dept. of Neuropathology, University Medical Center Göttingen (UMG), Göttingen, Germany.
Institute of Immunology, University of Heidelberg, Heidelberg, Germany.
Clin Chim Acta. 2018 Nov;486:1-7. doi: 10.1016/j.cca.2018.07.008. Epub 2018 Jul 10.
The complement system is a functional link between the innate and adaptive immune system and present in all compartments of the body. The composition of the cerebrospinal fluid (CSF) differs between the ventricular, cisternal and lumbar space. Usually, concentrations of blood-derived CSF proteins increase from ventricular to lumbar fractions.
In 20 geriatric patients with suspected normal pressure hydrocephalus (NPH) [13 women, 7 men, age 80.5 (75/85) years; median (25th/75th percentile)] a lumbar spinal tap of 40 ml was performed, and 10 ml of serum was drawn. CSF, sequentially collected in 8 fractions of 5 ml (1st fraction: lumbar CSF; 8th fraction: cisterna magna-near CSF), was analyzed for complement protein C3, and the activation products C3a and sC5b-9 by enzyme immunoassay.
The concentrations of the complement factors measured in fractions 1 and 8 of each individual patient were strongly correlated: C3 (Spearman's rank correlation coefficient r = 0.75, p = 0.0002); C3a (r = 0.93, p < 0.0001); sC5b-9 (r = 0.64, p = 0.002). CSF complement concentrations were lower in the cistern-near fraction 8 than in the lumbar fraction 1 (C3: p = 0.005; C3a: p = 0.0009; sC5b-9: p = 0.0003, Wilcoxon signed rank test). The concentrations of complement factors in CSF were two orders of magnitude lower than those in serum. C3 levels in the lumbar CSF strongly correlated with the lumbar CSF/serum albumin concentration quotient (Q) as a measure of the functionability of the blood-CSF barrier and the velocity of CSF flow (r = 0.84, p < 0.0001) suggesting diffusion of C3 from blood to CSF. The lumbar and cistern-near concentrations of C3a did not significantly correlate with Q (r = 0.26) pointing to a local conversion of C3 to C3a. The lumbar concentrations of sC5b-9 moderately correlated with Q (r = 0.62, p = 0.004). Plotting the CSF/serum quotient of C3 and sC5b-9 versus the Q revealed an approx. 50% local synthesis of C3, but a strong production of sC5b-9 in the CNS.
The increase of the complement concentrations from cisternal to lumbar CSF and the strong correlation of C3 with Q suggest that (1) a substantial portion of complement C3 in CSF originates from blood and (2) the complement system is mildly activated in the CSF of NPH patients.
补体系统是先天免疫系统和适应性免疫系统之间的功能联系，存在于身体的所有部位。脑脊液（CSF）的成分在脑室、蛛网膜下腔和腰椎间隙之间有所不同。通常，源自血液的 CSF 蛋白浓度从脑室分数增加到腰椎分数。
在 20 名疑似正常压力脑积水（NPH）的老年患者[13 名女性，7 名男性，年龄 80.5（75/85）岁；中位数（25 分位/75 分位）]中，进行了 40ml 的腰椎穿刺，并抽取了 10ml 的血清。CSF 依次收集 8 份 5ml （第 1 份：腰椎 CSF；第 8 份：小脑延髓池近 CSF），通过酶免疫分析法分析补体蛋白 C3 以及激活产物 C3a 和 sC5b-9。
每位患者的第 1 份和第 8 份脑脊液中测量的补体因子浓度呈强相关：C3（Spearman 秩相关系数 r=0.75，p=0.0002）；C3a（r=0.93，p<0.0001）；sC5b-9（r=0.64，p=0.002）。靠近小脑延髓池的第 8 份 CSF 中的补体浓度低于腰椎第 1 份（C3：p=0.005；C3a：p=0.0009；sC5b-9：p=0.0003，Wilcoxon 符号秩检验）。CSF 中的补体因子浓度比血清中的低两个数量级。腰椎 CSF 中的 C3 水平与腰椎 CSF/血清白蛋白浓度商（Q）强烈相关，这是衡量血脑屏障功能和 CSF 流动速度的指标（r=0.84，p<0.0001），表明 C3 从血液扩散到 CSF。腰椎和靠近小脑延髓池的 C3a 浓度与 Q 无显著相关性（r=0.26），提示 C3 在局部转化为 C3a。腰椎 sC5b-9 浓度与 Q 中度相关（r=0.62，p=0.004）。绘制 CSF/血清 C3 和 sC5b-9 商与 Q 的图表明，C3 的局部合成约为 50%，但中枢神经系统中 sC5b-9 的产生强烈。
补体浓度从蛛网膜下腔向腰椎 CSF 增加，以及 C3 与 Q 的强烈相关性表明（1）CSF 中的补体 C3 有相当一部分来自血液，（2）补体系统在 NPH 患者的 CSF 中轻度激活。
