Abstract
BackgroundMannan-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.MethodsMBL 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.ResultsMBL 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.ConclusionsMBL 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.
Highlights
Mannan-binding lectin (MBL), a protein of the innate immune response is attracting increasing clinical interest, in in relation to its deficiency
The free MBL molecule is a similar size to MBL correspondingly (IgM), the reference range of which was developed from a group of 4300 patients [1]
Nine out of thirteen patients in the control group showed cerebrospinal fluid (CSF)/serum concentration quotient of albumin (QMBL) values larger than the upper reference line Qlim (Figure 2, bold line), some with intrathecal fractions larger than 80% of the total MBL concentration in CSF. This clearly indicates that there is a dominant fraction of MBL in CSF that does not originate from blood
Summary
Mannan-binding lectin (MBL), a protein of the innate immune response is attracting increasing clinical interest, in in relation to its deficiency. Blood-CSF barriers and CSF flow rate Increased protein concentrations in the cerebrospinal fluid (CSF) of patients with neurological diseases, frequently ascribed to a blood-CSF barrier dysfunction, are due to pathologically-reduced CSF flow rates [1]. As there are no transport systems for the passage for proteins from blood to CSF, the CSF/serum quotient of a blood-derived fraction of any protein molecule for which we know the molecular size can be estimated [1,4] With this concept, which shows that a blood-CSF barrier dysfunction is not any kind of “leakage” at capillary structures but a consequence of the pathologically-reduced CSF flow rate, a change in QAlb can be interpreted as a change in CSF flow rate [1,4]. The influence of reduced CSF flow rate on proteins in CSF depends critically on the source of the proteins
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