Immunoglobulin intrathecal synthesis

The calculated intrathecal synthesis of IgG based on Reiber s formula is more precise in its latest version (see the recommended literature) and is recommended for the examination of cerebrospinal fluid in many countries. Physiological values for this formula are negative or equal to zero (software used for this purpose is able to recognize this). Negative values are considered to be equal to zero. Positive values indicate evidence of intrathecal synthesis of immunoglobulins (F3, R7). 

Although the examination of total protein in cerebrospinal fluid is quite valuable, it is necessary to mention that this parameter does not provide exact information on the function of the blood-CSF barrier. This is easy to understand. The increased concentration of total protein in cerebrospinal fluid can be based both on the failure of the barrier with a subsequent increase in the concentration of albumin and of other proteins originating from serum and on a more significant intrathecal synthesis of immunoglobulins, especially in levels of IgG. 

Classical electrophoresis is not suitable for the detection of intrathecal synthesis of immunoglobulins. 

The most characteristic abnormality in patients with multiple sclerosis is certainly the intrathecal synthesis of IgG. It can be demonstrated—with different sensitivity— by various methods, which can be divided into qualitative and quantitative methods. The gold standard for the demonstration of intrathecal synthesis of IgG is the detection of oligoclonal bands, which are not present in CSF, in the appropriately diluted serum (i.e., to the same concentration of IgG) by isoelectric focusing. This is a qualitative method and the description of its different modifications and interpretations goes beyond the scope of this chapter. This method is by far the most sensitive, and its sensitivity is reported between 90 and 100%. Here it is suitable to repeat that the detection of plasmocytic forms in cerebrospinal fluid may also be regarded as qualitative proof of intrathecal synthesis of immunoglobulins— although in this case the proof is obviously not specific for IgG from the theoretical point of view. 

In patients with multiple sclerosis, a qualitative cytological examination should always be carried out. Besides the finding of plasmocytic forms, which are considered to be one of the proofs of intrathecal synthesis of immunoglobulins, this examination also provides invaluable information concerning the reaction of the monocyte-macrophage system in the CSF compartment. It should be noted on the scope of biochemical examinations of cerebrospinal fluid in multiple sclerosis that it is most important to return to the simple and inexpensive method. 

Multiple Sclerosis (N = 55) Intrathecal Synthesis of Immunoglobulins According to Reiber s Eormula (S8)... 

Determination of acute-phase proteins (CRP, orosomucoid, haptoglobin, transferrin, prealbumin), immunoglobulins (IgA, IgG, IgM), compressive markers (albumin, fibrinogen), markers of tissue destruction (Apo A-I, A-II, Apo B), components of complement (C3, C4), proteinase inhibitors (antithrombin HI, a -antitrypsin). The measurement was performed simultaneously in CSF and in serum (plasma) by a laser nephelometric method. The functional state of the blood-CSF barrier was evaluated numerically with the help of the quotient Q = Albcsp/s and also by the intrathecal synthesis of immunoglobulins according to Reiber s formula and for each class—IgG, IgM, IgA. 

Changes of immunoglobulin concentrations in cerebrospinal fluid are very common. In neuroborreliosis the increase occurs very frequently in the IgM class, for which it is possible (using Reiber s formula) to demonstrate the presence of intrathecal synthesis. 

We investigated 53 samples of cerebrospinal fluid (CSF) in patients with neuroborreliosis. The clinical diagnosis of neuroborreliosis was confirmed by positive antibody titers and intrathecal synthesis of immunoglobulins in CSF examined in the IgM and IgG classes by the EFISA method or Western blot or confirmed by direct detection by PCR. 

Neuroborreliosis (A= 53) Intrathecal Synthesis of Immunoglobulins according to Reiber s Formula (S9)... 

Intrathecal Synthesis. Demonstration of increased intrathecal synthesis of immunoglobulins, particularly IgG, has great importance in the diagnosis of demyehnating diseases of the CNS, especially multiple sclerosis. In multiple sclerosis, patchy deterioration of myelin sheaths of axons in the CNS profoundly affects conduction of nerve impulses. 

Increased intrathecal synthesis of IgG causes an increase in the CSF/serum immunoglobulin concentration ratio and the appearance of oligoclonal immunoglobulin bands on electrophoretic separations of CSF. Investigation of these changes has now become routine when multiple sclerosis is... 

To appreciate the BBB and intrathecal (ith) synthesis of immunoglobulins, a blood specimen should be taken as well. 

Both aspects, the lack of an IgM-to-IgG switch and the slow normalization of intrathecal antibody synthesis, could be consequences of the same problem the handicapped regulation of the intrathecal immune response. Given the barrier-dependent low immunoglobulin concentration in CNS and the local (perivascular) invasion of relatively few immunocompetent cells, we might calculate a 10 lower probability for the encounter of cells and antibodies compared to blood. Irrespective... 

Antithrombin HI in cerebrospinal fluid can be easily denoted as an inflammatory marker. Correlations with levels of immunoglobulins, their intrathecal oligo-clonal synthesis, complement components, and acute-phase reactants confirm such concepts. Correlations with apolipoproteins and with the presence of lipophagic macrophages in cytological preparations confirm the elevation of CSF AT III levels when a destructive lesion of the CNS is present. 

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