Mannan-binding lectin in cerebrospinal fluid: a leptomeningeal protein

Fluids and Barriers of the CNS

Alberto Juan Dorta-Contreras³  Jens Christian Jensenius²  Barbara Padilla-Docal³  Hansotto Reiber¹ 

[1] Neurochemistry Laboratory, University Göttingen, Göttingen, Germany;Department of Biomedicine, University of Aarhus, Aarhus, Denmark;Labcel, Med.Sci. University Havana, Havana, Cuba

关键词: Blood- CSF barrier function;    Innate immune system in CNS;    Mannan binding lectin;    Leptomeninges;    Brain-derived proteins;    Blood-derived proteins;    Protein dynamics;    CSF Flow;    CSF;   

Others  :  807181
DOI  :  10.1186/2045-8118-9-17

 received in 2012-05-03, accepted in 2012-07-30,  发布年份 2012

【 摘 要 】

Background

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.

Methods

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.

Results

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.

Conclusions

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.

【 授权许可】

   
2012 Reiber et al.; licensee BioMed Central Ltd.

【 图 表 】

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