Neurochemistry Laboratory, University Göttingen, Göttingen, Germany.
Fluids Barriers CNS. 2012 Aug 13;9(1):17. doi: 10.1186/2045-8118-9-17.
Mannan-binding lectin (MBL), a protein of the innate immune response is attracting increasing clinical interest, in particularly in relation to its deficiency. Due to its involvement in brain diseases, identifying the source of MBL in CSF is important. Analysis of cerebrospinal fluid (CSF) can provide data that discriminates between blood-, brain-, and leptomeninges-derived proteins. To detect the source of MBL in CSF we need to consider three variables: the molecular size-dependent concentration gradient between CSF and blood, the variation in transfer between blood and CSF, and the CSF MBL concentration correlation with the albumin CSF/serum quotient (QAlb), i.e., with CSF flow rate.
MBL was assayed in samples of CSF and serum with an ELISA, coated with anti MBL antibodies. Routine parameters such as albumin-, immunoglobulin- CSF/serum quotients, oligoclonal IgG and cell count were used to characterize the patient groups. Groups comprised firstly, control patients without organic brain disease with normal CSF and normal barrier function and secondly, patients without inflammatory diseases but with increased QAlb, i.e. with a blood CSF barrier dysfunction.
MBL concentration in CSF was at least five-fold higher than expected for a molecular-size-dependent passage from blood. Secondly, in a QIgM/QAlb quotient diagram (Reibergram) 9/13 cases showed an intrathecal fraction in some cases over 80% of total CSF MBL concentration 3) The smaller inter-individual variation of MBL concentrations in CSF of the control group (CV = 66%) compared to the MBL concentrations in serum (CV = 146%) indicate an independent source of MBL in CSF. 4) The absolute MBL concentration in CSF increases with increasing QAlb. Among brain-derived proteins in CSF only the leptomeningeal proteins showed a (linear) increase with decreasing CSF flow rate, neuronal and glial proteins are invariant to changes of QAlb.
MBL in CSF is predominantly brain-derived and all results pointed to the leptomeningeal cells as the source of the protein. The evaluation of this protein requires the interpretation of its absolute concentrations in CSF as a function of the albumin quotient, QAlb. This recognition of MBL in brain cells opens a new field of discussion about the function of the innate immune response in CNS in cases of acute and chronic neurological diseases.
甘露聚糖结合凝集素（MBL）是先天免疫反应的一种蛋白，越来越受到临床关注，特别是与它的缺乏有关。由于其与脑部疾病有关，因此确定 CSF 中 MBL 的来源很重要。分析脑脊液（CSF）可以提供区分血液、脑和软脑膜来源蛋白的数据。为了检测 CSF 中 MBL 的来源，我们需要考虑三个变量：CSF 和血液之间分子大小依赖的浓度梯度、血液和 CSF 之间转移的变化，以及 CSF MBL 浓度与白蛋白 CSF/血清商（QAlb）的相关性，即与 CSF 流速有关。
我们使用 ELISA 检测 CSF 和血清样本中的 MBL，该 ELISA 用抗 MBL 抗体包被。我们使用常规参数，如白蛋白、免疫球蛋白 CSF/血清商、寡克隆 IgG 和细胞计数来描述患者组。这些组包括：1）无器质性脑疾病、CSF 正常和血脑屏障功能正常的对照组患者；2）无炎症性疾病但 QAlb 升高的患者，即血脑屏障功能障碍。
1）CSF 中 MBL 的浓度至少是根据分子大小从血液中预期的通过量的五倍。2）在 QIgM/QAlb 商图（Reibergram）中，9/13 例在某些情况下显示出鞘内分数超过 CSF 总 MBL 浓度的 80%；3）与血清相比，对照组 CSF 中 MBL 浓度的个体间变异（CV=66%）较小，而血清中 MBL 浓度的个体间变异（CV=146%）较大，这表明 CSF 中 MBL 有独立的来源。4）CSF 中 MBL 的绝对浓度随 QAlb 的增加而增加。在 CSF 中的脑源性蛋白中，只有脑膜蛋白随着 CSF 流速的降低而呈（线性）增加，神经元和神经胶质蛋白对 QAlb 的变化不变。
CSF 中的 MBL 主要来源于脑，所有结果均表明该蛋白来源于脑膜细胞。评估这种蛋白需要将其 CSF 中的绝对浓度作为白蛋白商 QAlb 的函数进行解释。这种对脑细胞中 MBL 的识别为急性和慢性神经疾病时中枢神经系统中先天免疫反应的功能开辟了一个新的讨论领域。
