Cerebrospinal fluid immunoglobulin quotients, kappa/lambda ratios, and viral antibody titres in neurological disease.

Abstract

It was also found that the quotient CSF/serum IgG, expressed as a percentage of the CSF/serum albumin, was better in distinguishing patients with definite or suspected MS from those with other neurological disorders than the quotients IgG/albumin or IgG/total protein.The CSF K/A ratio and the CSF and serum complement-fixing antibody titre to measles and herpes simplex virus were measured in many of the patients. In general, abnormalities of these measurements were associated with raised IgG/albumin quotients. However, in eight patients with definite or suspected MS, a normal IgG/albumin quotient was found with abnormal CSF K/A ratios (6 cases) or abnormal CSF titres of measles antibody (7 cases). In addition, two patients with HSVE had normal IgG/albumin ratios but detectable herpes antibody in the CSF.These findings suggest that the measurement of the relative concentration of CSF immunoglobulin in combination with the K/A ratio and antibody titre to various viruses may supplement each other in the endeavour to detect central nervous system immunoglobulin synthesis in neurological diseases.In normal individuals, immunoglobulin in the CSF is derived from the plasma by diffusion across the blood/CSF barrier (see Schultze and Heremans (1966) Chapter 3 for review). Rosenthal and Soothill (1962) have shown that the quantity of this CSF immunoglobulin is dependent on the serum immunoglobulin concentration, the molecular size of the immunoglobulin, and the permeability of the blood/ CSF barrier. Thus for healthy individuals IgM is totally excluded from the CSF owing to its large size and low plasma concentration but may be present in conditions in which a gross defect in the

Total protein is an effective loading control for cerebrospinal fluid western blots

“…Second, our individual samples comprised ALS and healthy control subjects. Large differences in protein content (including albumin levels) between disease and control CSF samples are well documented [27, 54-57]. These differences are likely averaged out in the pooled samples, which comprise ALS, AD, and healthy control subjects.…”

Disproportionate elevation of the immunoglobulin G1 concentration in cerebrospinal fluids of patients with multiple sclerosis

“…It was necessary for the interpretation of IgG subclass concentrations in the various groups of persons to construct a frame of reference which had to provide tools for the detection of disproportionately elevated IgG concentrations in the CSF, thereby giving a measure for local IgG synthesis in the subarachnoid space. This information could be obtained by several methods (4,9,12,21,25). The procedure described by Delpech and Lichtblau 4is based on a correlation of the IgG/albumin ratios in CSF and serum, which implies the strict requirement of simultaneous collection of the CSF and corresponding serum specimens.…”

“…Local immunoglobulin G (IgG) production in the subarachnoid space is a hardly understood phenomenon which occurs in patients with chronic inflammatory diseases of the central nervous system (7,12,22,25). To reveal the underlying mechanisms and the significance of this phenomenon, a detailed characterization of the cerebrospinal fluid (CSF) IgG fraction is in progress with regard to different molecular properties, such as antibody specificity (21,27,28), light-chain ratios (1,2,16,21), electrophoretic mobility, isoelectric point (5,13,28,29), and IgG subclass membership (29). Tourtellotte (25) proposed a formula which can calculate the amount of IgG synthesized per day in the subarachnoid space.…”

Detection of oligoclonal IgG kappa and IgG lambda bands in cerebrospinal fluid and serum with HevyliteTM antibodies. Comparison with the free light chain oligoclonal pattern.

“…Nevertheless, lowering the detection limit is of crucial importance for oligoclonal fLC analysis, since these are present in much lower concentrations in the CSF. Several authors have reported altered CSF kappa/ lambda ratios [4][5][6][7]11,21] as well as predominance of kappa (using free and bound anti-light chain antisera) OCBs [8,10,22] in a proportion of patients with MS. Such conclusions could not be reached in our methodological study due to a low number of patients tested.…”

“…It may be of interest to determine whether these bands are predominantly IgG or IgGλ. Previous reports used either quantitative tests [4][5][6][7] or immunofixation with kappa and lambda antisera [8][9][10] to demonstrate altered kappa/lambda or oligoclonal kappa/lambda ratios. However, these tests were not able to directly distinguish individual heavy-light chain pairs.…”