CSF IgG Research Articles

Studies on the humoral and cell-mediated immune response in a patient with Mollaret's meningitis

A patient with Mollaret's meningitis with protracted course and a strong immune response within the central nervous system is described. The findings of IgG bands in agarose gel electrophoresis of CSF together with elevated CSF IgG index values are in accordance with intrathecal synthesis of IgG, possibly against an antigen persistent in the CNS. Subgrouping of CSF lymphocytes morphologically (B/T, active T cells) and functionally (stimulation with mitogens) showed that these cells differed from peripheral blood lymphocytes. A defect in the regulatory function of T cells may be responsible for the continuing pathologic process in Mollaret's meningitis.

Predominance of oligoclonal IgG type lambda in CSF in aseptic meningitis.

Oligoclonal immunoglobulins (Ig) demonstrble as bands by agarose-gel electrophoresis of CSF were characterized in ten patients with aseptic meningitis. Oligoclonal CSF IgG was found in all patients, IgM was found in two. The oligoclonal Ig was more often of lambda light-chain type than of kappa type. In four patients, oligoclonal Ig bands contained kappa and lambda light chains simultaneously. In two patients, bands consisting of free lambda light chains were found. On repeated investigations more than one year later in three cases, the oligoclonal IgG was of the same light-chain type. The immune response within the CNS in aseptic meningitis seems to be dominated by synthesis of IgG with lambda light chains.

Characterisation of the mobility on isoelectric focusing of individual proteins in CSF and serum by immunofixation.

The mobility of 17 different proteins in CSF and serum on isoelectric focusing was investigated by subsequent immunofixation using monospecific antisera. Individual proteins yielded identical, often complex band patterns in normal CSF and serum, except transferrin which gave one to two additional bands between pH 5.8-6.4, and the low molecular wieght beta-trace protein and gamma-trace protein, which gave three bands at pH 7.4, 8.0, and 8.4, and a single band at pH 9.5, respectively, on investigation of CSF but not serum. Polyclonal IgC migrated as multiple bands between pH 4.7-8.6. Oligoclonal IgG in CSF in multiple sclerosis and neurosyphilis migrated between pH 8.6-9.5 and was easily discriminated from other proteins.

HLA-typing and lymphocyte population studies in patients with multiple sclerosis

Compared to a control population, the frequency of HLA-B7 was increased in a group of 46 patients with a chronic progressive form of multiple sclerosis (MS) (RR = 2.9, P = 0.01). Significance of the association was lost after correction for first order error. Results on serotyping for “B-cell DW2” antigen are suggestive of an increased frequency of this antigen in chronic progressive MS patients (RR = 2.9, P = 0.01). The percentage of T-cells (E-rosette forming lymphocytes) in MS patients was lower (mean 46 ± 17%, n = 34) than in a control group (mena 62 ± 10%, n = 90). Only 5 of the 40 patients had high B-lymphocyte percentages, whereas no difference in B-cell counts was observed between the total group of patients and the control group. The T- and B-lymphocyte ratio in the MS patients was lower than in the control group. The 7 patients with the lowest T/B-cell ratio were negative for “B-cell DW2” antigen. In 3 patients, the sum of T plus B-lymphocytes was far lower than 90%. At least 4 patients had in their serum antibodies against autologous lymphocytes as found by immunofluorescence tests. No correlation could be found between these serological and immunological data and clinical data on progression of the disease, the IgG in CSF and improvement after immunosuppressive treatment.

Quantitation of Measles Virus-Specific Immunoglobulins in Serum, CSF, and Brain Extract from Patients with Subacute Sclerosing Panencephalitis

Abstract The amount of measles-specific IgG in sera, CSF, and brain extracts from patients with SSPE was determined by radial immunodiffusion method with the use of a number of rabbit antisera specific for human γ-chain, after each sample was abosrbed suitably with a lyophilized preparation of measles-precipitating antigen (MPA) made in Vero cells infected with Edmonston strain of measles virus. The measles-specific IgG contents of the sera ranged from approximately 10 to 20% and those of CSF and brain extracts from 25 to 75% of the total IgG, indicating a synthesis of measlesspecific IgG within the CNS. By employing the same method, a significant amount of measles-specific IgM was demonstrated in sera of three out of six SSPE patients. Sera, CSF, and brain extracts from controls when absorbed with MPA and quantitated by the same method did not show significant amounts of measles-specific IgG. When the agarose gel electrophoretic patterns of unabsorbed and MPA-absorbed SSPE brain extracts were compared, the absorbed extracts were found to lack homogeneous bands in a γ-globulin region in contrast to the presence of two to three homogeneous IgG bands seen in the unabsorbed brain extracts. On the other hand, the patterns of unabsorbed and absorbed SSPE sera did not show such a significant difference in γ-globulin region. These data strongly support the concept that measles virus is responsible for the formation of homogeneous bands within the CNS in SSPE.

Central nervous system involvement in sle

The clinical course and diagnostic profile of 13 patients with central nervous system involvement and systemic lupus erythematosus (CNS-SLE) are presented. The diagnostic yield for each procedure was measured as the precent abnormal: CSF total protein was 38%; increased CSF IgG 69%; decreased CSF hemolytic C4 10%; increased CSF anti-DNA 64%; electroencephalogram 80%; flow brain scan 50%; and static brain scan 0%. No single procedure was consistently abnormal, but the battery of tests provided a useful and specific CNS-SLE diagnostic profile.

Relation between genetic markers and oligoclonal IgG in CSF in optic neuritis

Thirty patients with acute, unilateral optic neuritis (ON), where re-examination after a mean observation period of 5 years did not reveal any aetiology, were investigated with regard to laboratory abnormalities frequently observed in multiple sclerosis. Eleven patients had oligoclonal IgG in CSF. In 5 of these a measles virus antibody response within the CNS was demonstrable. The remaining 19 patients did not display oligoclonal CSF IgG, nor an antibody response. The major histocompatibility antigens HL-A3 and HL-A7 occurred at similar frequencies in ON and in controls, irrespective of the presence of oligoclonal CSF IgG. The HL-A7 associated MLC determinant LD-7a occurred in ON at a frequency between that observed in controls and in MS. However, an association of the same magnitude as observed in MS was found between ON with oligoclonal CSF IgG and the presence of LD-7a. This association was absent in those ON patients who lacked oligoclonal CSF IgG. The present data indicate that the finding of oligoclonal CSF IgG may increase the risk of developing MS.

Reduced CSF IgG in patients treated with phenytoin (diphenylhydantoin).

In the CSF's from 13 out of 30 phenytoin-treated patients the IgG concentrations were lower than the lowest amont 20 controls, while only 3 out of 37 patients with brain lesions without epilepsy had so low IgG value. Titers of IgG antibodies to rabbit erythrocytes were similar in the three groups. It should be kept in mind, when evaluating results of IgG determinations in clinical neurology, that reduced IgG may be a consequence of phenytoin treatment. Reduced IgG concentrations without reduction of an antibody belonging to the IgG class indicate that the suppression of immunoglobulin synthesis by phenytoin may be selective.

Demonstration of oligoclonal immunoglobulin G IN Guillain-Barré syndrome.

Elevated concentrations in CSF of the immunoglobulins G, A, and M, when expressed as a percentage of the total protein concentration of CSF, were demonstrated during the initial phase of the course of the disease in a patient with Guillain-Barre syndrome (GBS). A slight elevation of the relative concentrations of IgG and IGM in CSF were also registered later in the course of the disease, at the time when the patient's neurological symptoms were in regression. Multiple discrete IgG bands were demonstrated by agarose electrophoresis in serum and in CSF during the first 2 weeks after onset of the neurological symptoms, and also after week 2 and still during week 12 after onset. The finding of transient oligoclonal IgG in a parient with GBS may suggest stimulation with e.g. viral antigen.

Cerebrospinal fluid findings in patients with optic neuritis.

Cerebrospinal fluid specimens (CSF) from 59 patients with optic neuritis and from 59 age‐matched neurological control patients were studied. The patients with optic neuritis showed significantly higher CSF IgG concentrations and a higher frequency of abnormal CSF electrophoresis as compared with the control specimens. Elevated relative IgG values (expressed as percentage of CSF total protein concentration) were noticed in 42%, abnormal electrophoresis in 41%, pleocytosis in 26% and increased total protein concentrations in 29% of CSF specimens from patients with optic neuritis. Thirty patients with an unknown cause of optic neuritis and without any neurological symptoms other than optic neuritis, showed increased relative IgG in 40%, abnormal electrophoresis in 31%, pleocytosis in 33% and increased total protein concentration in 27% of CSF specimens. A reduced serum/CSF albumin ratio was noticed in high frequency in patients with optic neuritis indicating possible blood brain barrier damage. There were, however, 13 patients with optic neuritis and two from the control group with normal serum/CSF albumin ratio but reduced serum/CSF IgG ratio. This finding supports the presumption that part of CSF IgG is produced within the central nervous system (CNS).

Determination of IgG heavy chains by electroimmuno-diffusion in the nanogram range: Simultaneous application to serum and csf of neurological patients

A new method for the determination of IgG heavy chain by electroimmuno-diffusion is described: the sensitivity reaches 1 mg/1 using 5 μ1 only ( i.e.: 5 nanograms). Results of simultaneous determinations in serum and CSF are given and discussed: the study of a neurological population (102 patients = among these 61 cases of multiple sclerosis) suggests a general lack of correlation between serum and CSF IgG levels.

Serum IgG, IgA and IgM concentration in 1,038 patients with various neurological disorders.

Concentration of serum IgG, IgA and IgM in 1,038 unselected patients with various neurological diseases was determined. In 521 instances, the levels of CSF IgG, IgA and IgM were also established. In serum, the most frequent selective quantitative abnormality was found in the IgA concentration. In CSF, an increased level of IgG with normal IgA concentration and undetectable IgM was established about 8 times more frequently than isolated increase of CSF IgA. Selective quantitative abnormalities in serum IgG were observed in 35% of patients with subacute sclerosing panencephalitis as compared to 5% in instances in the “definite” MS group. Abnormal bands in the serum gamma-globulin field were most frequently seen in electropherograms from patients with subacute sclerosing panencephalitis, in cases of malignant lymphoproliferative disorders and in patients with “definite” MS. No correlation between the concentration of serum and CSF immunoglobulins could be established. Most frequent quantitative abnormalities in serum IgG, IgA and/or IgM were established in malignant lymphoproliferative disorders, in patients with myopathies including myositides and in subacute or chronic inflammatory CNS disorders. Highest incidence of increased CSF IgG, IgA and/or IgM concentration was detected in patients with inflammatory CNS disease, in instances of “definite” MS and in malignant lymphoproliferative disorders with CNS symptomatology. Increased CSF IgG and IgA concentration with detectable levels of IgM in patients with elevated CSF total proteins indicated alterations in the blood/CNS barrier structures.

Manual and Automated Determination of Immunoglobulins in Unconcentrated Cerebrospinal Fluid

Abstract Manual procedures have been developed for determination in human cerebrospinal fluid of the immunoglobulins IgG, IgA, and IgM. An automated continuous-flow procedure for determination of IgG in human CSF is also described. The immunoglobulins are quantitated in both cases by immunoprecipitin reactions, with use of commercial antiserum. Values determined for the immunoglobulins by the manual method correlate with values for gamma globulin obtained by electrophoresis. The values for IgG from the manual method also correlate with IgG values determined by the automated procedure. The precision of duplicate determinations with the manual procedures for IgG, IgA, and IgM is 3.4, 1.8, and 1.0% (relative standard deviation), respectively, and that for lgG with the automated system is 3.48%.

Gm and Inv antigenic character of serum and cerebrospinal fluid IgG in multiple sclerosis.

Antigenic analysis of γ-globulins in the CSF of controls and patients with multiple sclerosis showed no gross deficiency in Gm or Inv typing. Concordant typing for Gm and Inv factors from serum and CSF identifies the antigenic completeness of IgG in both control and multiple sclerosis CSF. No support was obtained for the possibility that individuals with multiple sclerosis differ from controls in Gm or Inv(a) serotypes.