Cerebrospinal Fluid Immunoglobulin Research Articles

Cerebrospinal fluid immunoglobulin abnormalities in neurosarcoidosis.

A retrospective chart review of neurosarcoidosis at the University of Texas Medical Branch (Galveston) between 1982 and 1987 revealed 99 patients with sarcoidosis. Six patients were diagnosed with neurosarcoidosis and had electrophoresis of serum and cerebrospinal fluid performed (one patient with a ventriculoperitoneal shunt was later excluded). Cerebrospinal fluid immunoglobulins and albumin levels were determined followed by calculation of an IgG index and synthesis rate for each patient. Four (80%) of five patients had elevated IgG indexes and synthesis rates indicative of intrathecal immunoglobulin production. No patient had immunoglobulin oligoclonal bands detected. To date, results of electrophoresis of cerebrospinal fluid in neurosarcoidosis have been reported in 37 patients among four series. Of these, only nine patients (24%) have had either an elevated IgG index or synthesis rate. Our series suggests that intrathecal immunoglobulin production in neurosarcoidosis occurs more frequently than previously described. Furthermore, the elevated indexes and synthesis rates without associated oligoclonal bands suggests a polyclonal immunoglobulin response.

Kappa/Lambda Ratios In IgG, IgA and IgM of Cerebrospinal Fluid and of Sera in Patients with Multiple Sclerosis

Kappa/lambda (kappa/lambda) ratios of each immunoglobulin, i.e. IgG, IgA and IgM in cerebrospinal fluid (CSF) and in sera of patients with multiple sclerosis (MS) were analysed by sandwich enzyme linked immunosorbent assay. In CSF kappa/lambda ratios of IgG of MS patients were significantly (p less than 0.05) higher than those of normal controls, whereas the values of IgA and IgM did not differ significantly from those of normal controls. In sera kappa/lambda ratios of IgG, IgA and IgM did not differ significantly from those of normal controls. Our results suggest that in MS patients abnormal kappa/lambda ratios are also restricted to IgG components in CSF, as oligoclonal IgG bands are.

Comparative analysis of virus-specific antibodies and immunoglobulins in serum and cerebrospinal fluid of subacute measles virus-induced encephalomyelitis (SAME) in rats and subacute sclerosing panencephalitis (SSPE)

The intrathecal humoral immune response was analysed in patients with subacute sclerosing panencephalitis (SSPE) and Lewis rats with subacute measles virus (MV)-induced encephalomyelitis (SAME). SSPE patients as well as SAME rats revealed oligoclonal, intrathecal antibody synthesis with MV specificity. SAME rats synthesized MV-specific antibodies intracerebrally to a higher extent than SSPE patients. Although a restricted isoelectric pattern of MV-specific antibodies was detected in the cerebrospinal fluid (CSF) of SSPE patients as well as of SAME rats, the heterogeneity within clusters of immunoglobulin bands was higher in the rat specimens. Increase in the blood-brain barrier permeability for albumin was exclusively detected in SAME rats but not in SSPE patients. These data suggest that the rat model offers excellent opportunities to study the initial humoral events in MV-induced encephalitides.

Cerebrospinal fluid immunoglobulins and virus-specific antibodies in disorders affecting the facial nerve.

Sixty-two patients with acute idiopathic peripheral facial nerve palsy (AIPFP) and 31 patients with lymphocytic meningoradiculitis (Garin-Bujadoux or Bannwarth's syndrome) are described. Results of cerebrospinal fluid (CSF) analysis, including the measurement of immunoglobulins (Ig) G, A, and M, indicate that pleocytosis and/or disturbance of the blood-CSF barrier (BCB) and/or local immunoglobulin synthesis within the central nervous system (CNS) do occur in about 25% of patients with AIPFP. The commonest finding is a slight to moderate breakdown of BCB function without evidence of intrathecal immunoglobulin synthesis. In only about 10% of patients, further support for an inflammatory process within the CNS is found by intrathecal synthesis of oligoclonal IgG and/or localized synthesis of IgG and/or IgA. The majority of cases (75%) do not show any signs of an inflammatory process within the CNS. In contrast, lymphocytic meningopolyradiculitis (LMR) has a characteristic CSF profile with early impairment of BCB permeability as well as with rapid and predominant intrathecal IgM synthesis, which helps to distinguish monosymptomatic LMR from AIPFP. By applying a sensitive enzyme-linked immunosorbent assay to identical concentrations of IgG in serum and CSF, evidence of intrathecal synthesis of virus-specific antibodies was found only in 2 of 13 patients with AIPFP. In contrast, all 4 patients with herpes zoster oticus and peripheral facial palsy (Ramsay Hunt syndrome) showed an intrathecal IgG synthesis to varicella zoster virus lasting for up to 4 months after onset of disease.

T‐Lymphocyte Subpopulation Levels and Immunoglobulin Changes in the Cerebrospinal Fluid of Patients with Neurologic Disorders

Immunologic mechanisms are thought to play an important role in the pathogenesis of multiple sclerosis (MS). In this study we examined cerebrospinal fluid (CSF) samples of 29 patients with MS and of 24 patients with other neurological disorders. An elevated T-helper (Th)/T-suppressor (Ts) ratio was typical for the CSF of patients with MS. There was a clear positive correlation between the percentage of Th cells and the existence of oligoclonal bands in the CSF. On the other hand, the percentage of Ts cells correlated negatively with the existence of oligoclonal bands in the CSF. The imbalance of CSF T-lymphocyte subpopulations may be one of the fundamental defects in MS, and the observed alterations in CSF immunoglobulin synthesis pattern might only reflect these changes.

Effect of early and late syphilis on central nervous system: cerebrospinal fluid changes and neurological deficit.

Neurological examination and investigation of the cerebrospinal fluid (CSF) was performed on 24 patients with early and 180 patients with late syphilis. In 21 (12%) patients with late syphilis positive CSF treponemal test results and neurological deficits suggestive of symptomatic neurosyphilis were found. Concomitantly all but three patients with neurosyphilis showed one or more of the following abnormal CSF variables: CSF concentration of albumin X 10(3)/serum concentration (albumin ratio) greater than or equal to 7.9; mononuclear cells greater than 5 microliters: ratio of CSF to serum IgG concentrations/ratio of CSF to serum albumin concentrations (IgG index) greater than or equal to 0.7 or of IgM/albumin (IgM index) greater than or equal to 0.1; or oligoclonal CSF immunoglobulins. In 20 (95%) patients with neurosyphilis evidence of the production of treponemal antibodies within the central nervous system (CNS) was shown. Ten (48%) patients with neurosyphilis had been treated previously for late syphilis. These observations emphasise the need to screen for neurosyphilis in patients with late syphilis. Intrathecal production of treponemal antibodies was detected in six (25%) patients with early and 44 (28%) with late syphilis who did not show any neurological deficit. Intrathecal production of treponemal antibodies indicating that the CNS was affected led us to suspect asymptomatic neurosyphilis in these patients. Seventeen (11%) patients with late syphilis but no neurosyphilis and only one (4%) with early syphilis showed additional abnormal CSF variables. Surprisingly, six out of 22 patients with treated early and 20 out of 68 patients with treated late syphilis showed evidence of treponema antibody production within the CNS. We do not know whether these findings indicate that the CNS was affected because of inadequate treatment or merely reflect persistent synthesis of treponemal antibodies associated with cured infection. In one (4%) patient with early and in 21 (13%) with late syphilis but no neurosyphilis abnormal CSF variables in the absence of positive CSF treponemal test results were observed, which excluded syphilitic inflammation of the CNS.

Monosymptomatic sensory symptoms and cerebrospinal fluid immunoglobulin levels in relation to multiple sclerosis.

Of 53 patients with monosymptomatic paresthesiae, 55% had oligoclonal bands and 28% an elevated cerebrospinal fluid (CSF) IgG index. Over a mean observation period of 64 months, nine patients developed clinically definite multiple sclerosis (MS); all of these patients had IgG bands, illustrating the prognostic importance of this CSF aberration. Two lumbar punctures more than one year apart were performed in 31 of the patients, of whom 20 had oligoclonal bands. This abnormality was constant between the time of punctures in all subjects except one, thus behaving as in MS. Similarly, the CSF findings in the 11 patients without oligoclonal bands remained normal over the observation period. The majority of patients with oligoclonal bands had cells in their CSF producing immunoglobulin of one or more of the three main classes, while none of those without oligoclonal bands displayed immunoglobulin-producing cells in CSF. Occurrence of oligoclonal bands in CSF is common in patients with paresthesiae and increases the risk for future development of MS.

Immunoglobulins in serum and cerebrospinal fluid from patients with acute Guillain-Barré syndrome.

IgG, IgA, IgM and IgE were quantified in serum and IgG and total protein were quantified in cerebrospinal fluid (CSF) from 80 patients with acute Guillain-Barré syndrome. The serum concentrations of IgM and IgA were significantly increased in approximately 25% of the patients, whereas the concentrations of IgG and IgE were normal. Increased CSF concentrations of IgG were found in more than 90% of the patients and correlated with increased CSF total protein concentrations. The CSF IgG/total protein ratio, CSF IgG index and Tourtellotte's formula were used to determine intra-thecal IgG synthesis in 30 of the patients. In eight of the patients the results of the CSF IgG index and Tourtellotte's formula were significantly increased, while in the remaining seven patients increased values were obtained using only one of these formulae. The CSF IgG/total protein ratio was normal in all the patients. Oligoclonal bands were not detected in any of the sera or CSF. Antibodies to peripheral nerve tissue were detected in approximately 30% of the patient sera, but could not be detected in the CSF.

Immunological Disturbances in Psychiatric Patients-Reply

<h3>n Reply.—</h3> Our recent study¹showed no elevation of immunoglobulin levels or increased incidence of oligoclonal immunoglobulin in a group of psychiatric patients compared with controls. Although these data suggest that viruses and autoimmunity are not involved in the major psychoses, the study has certain limitations that are detailed in our article and reiterated in Dr DeLisi's letter. Most individuals with persistent CNS infections have raised cerebrospinal fluid (CSF) immunoglobulin levels, but immunosuppressed individuals may have chronic viral infections with little evidence of immunoglobulin level elevations. In addition, unconventional agents and autoimmune processes may not produce quantitative or qualitative immunoglobulin abnormalities. Most investigators have found, however, that CSF immunoglobulin level elevations and bands have been found consistently in persistent viral encephalitis caused by conventional agents in immunocompetent hosts, eg, 100% of patients with subacute sclerosing panencephalitis and herpes simplex encephalitis^2,3have increased CSF IgG levels and bands.⁴

Two‐dimensional gel electrophoresis of cerebrospinal fluid immunoglobulins

AbstractWith the aid of two‐dimensional electrophoresis, the immunoglobulins (Ig) in cerebrospinal fluid (CSF) were separated into heavy and light chains and visualized with silver staining. CSF from 36 patients with no abnormal immunologic activity in the central nervous system show a constant pattern of light chain subfractions, however varying strongly in their respective quantities. In 40 patients with inflammatory diseases such as confirmed multiple sclerosis (MS) (n = 10), neurosyphilis (n = 6), lymphocytic meningoradiculitis (n = 3), novel immunoglobulins appear and form a so‐called oligoclonal zone in the light chain region. By comparing various oligoclonal zones, differences were found between the arrangement of the novel Ig light chains and the polyclonal light chain background. In the region of the polyclonal light chain background certain protein fractions appear which are non‐immunoglobulin and which are not found in serum. The protein fraction at the isoelectric point of 7.8 appears in 9 out of 10 confirmed MS cases, but in none of the 6 neurosyphilis and 3 lymphocytic miningoradicultis cases. In one case of neurosyphilis with an extremely high gamma‐globulin content in CSF we found an oligoclonal zone in the heavy chain region.

Cerebrospinal Fluid IgM, IgA, and IgG Indexes in Systemic Lupus Erythematosus

Paired serum and cerebrospinal fluid (CSF) specimens from 13 patients with systemic lupus erythematosus (SLE) and central nervous system involvement (CNS-SLE) were studied for CSF IgM, IgA, and IgG indexes (indicators of intrathecal immunoglobulin synthesis) and CSF-serum albumin quotient (Q albumin) (an indicator of blood-brain-barrier function). We also studied 20 patients with noninflammatory neurologic diseases and seven patients with SLE without CNS involvement for comparison. In addition to an increase in the CSF IgG index, IgM and IgA indexes also were elevated in patients with CNS-SLE. All three indexes decreased significantly when CNS manifestations subsided by successful treatment. The Q albumin was normal in most patients. The elevation of CSF immunoglobulin indexes may be a result of polyclonal B-lymphocyte activation within the CNS, rather than the leak of immunoglobulins from the systemic circulation into the CNS. Since these indexes reflect CNS disease activity in SLE, they may be a successful tool for the management of SLE.

Examinations of cerebrospinal fluid immunoglobulin G by chromatofocusing.

IgG components in the CSF and paired sera were examined by chromatofocusing. The separations were performed using the FPLC system with a mono P column and were based on a pH gradient between 9.5 and 6.0. A total amount of 0.1 mg IgG was applied to the column. All samples with oligoclonal IgG were easily identified and the findings differed clearly from those of normal IgG. The sensitivity, resolution capacity and relatively fast as well as easy performance make chromatofocusing a promising tool for investigations of IgG in the CSF.

Quantitation of IgG, IgA and IgM in the cerebrospinal fluid by a solid-phase enzyme-immunoassay: Establishment of normal control values

A sensitive, specific and simple solid-phase enzyme-immunoassay for quantitative determination of IgG, IgA and IgM in the cerebrospinal fluid (CSF) has been developed. Using this technique, we have established the control values for CSF immunoglobulins from 30 neurologically normal subjects. The value of IgG determined by our method was closely correlated with that found by single radial immunodiffusion although the latter was found 1.5 times higher. The values of IgG and IgA showed significant positive correlations with CSF total protein values, while the value of IgM did not. This finding suggested that the concentration of CSF IgM might be less affected by transudation from the serum than those of IgG and IgA in neurologically normal subjects. Our method needs no complicated technique nor special apparatus other than microplate photometer, and offers more facility and convenience for routine laboratory use.

Cerebrospinal fluid immunoglobulin D in myasthenia gravis.

Journal Article Cerebrospinal fluid immunoglobulin D in myasthenia gravis. Get access R Prasad R Prasad Search for other works by this author on: Oxford Academic Google Scholar Clinical Chemistry, Volume 29, Issue 8, 1 August 1983, Pages 1561–1562, https://doi.org/10.1093/clinchem/29.8.1561 Published: 01 August 1983

Assessment of cerebrospinal fluid immunoglobulin patterns after isoelectric focusing: Use of kappa and lambda light chain immunoperoxidase staining

Assessment of the presence of immunoglobulin (Ig) of restricted heterogeneity i.c. oligoclonal Ig in cerebrospinal fluid subjected to isoelectric focusing (IEF) may be difficult because of the tendency of the technique to subdivide even normal polyclonal IgG into bands and zones. Focused Ig stained by the immunoperoxidase technique for kappa and lambda light chains shows correspondence between the two patterns in the case of normal polyclonal Ig, but a marked discrepancy between kappa and lambda patterns in disorders associated with oligoclonal Ig, and kappa and lambda immunofixation makes assessment of agarose IEF separations of IgG more reliable.

Cerebrospinal fluid immunoglobulins in sheep with visna, a slow virus infection of the central nervous system

Icelandic sheep were injected intracerebrally with visna virus, which produces a persistent infection of the CNS accompanied by encephalomyelitis and focal demyelinating lesions. Studies were conducted on two groups of sheep, with short-term infections (25 sheep sampled 1–3 months after infection) and long-term infections (14 sheep sampled 5–6 years after infection). Quantitative determination of CSF immunoglobulin levels 5 years after infection indicated that IgM concentrations was usually elevated, IgG2 was occasionally elevated and IgG1 was rarely elevated. CSF oligoclonal bands were seen in about half the sheep examined 5 years after infection. There was a correlation between high titers of CSF antiviral antibody and both elevated CSF IgM concentration and CSF oligoclonal bands. Serum/CSF IgG1 ratios indicated that the blood-brain barrier was apparently intact in long-term visna infection, consistent with intrathecal synthesis of IgM and of antiviral antibody. The alterations in CSF immunoglobulins in visna resemble those found in other persistent CNS virus infections and in multiple sclerosis.

Immunoglobulins in cerebrospinal fluid in central nervous system disorders.

Immunoglobulins were estimated in the cerebrospinal fluid from 70 cases of nervous system diseases. Thirty childern with evidence of C.N.S. irritation without infection served as controls. The immunoglobulins were higher in cases with C.N. S infections. Within this group meningeal involvement (tubercular and pyogenic) resulted in a significant rise in IgG compared to viral encephalitis. The proportion of immunoglobulin in the CSF protein can be helpful in distinguishing TBM from PM.

Virus antibodies in Parkinson's disease: Herpes simplex and measles virus antibodies in serum and CSF and their relation to HLA types

Serum and cerebrospinal fluid (CSF) immunoglobulin G (IgG) antibodies to herpes simplex (HSV) and measles viruses were assayed with a radioimmunoassay in 56 patients with idiopathic Parkinson's disease and in a similar number of age- and sex-matched controls with other neurological diseases. As a group, the patients with Parkinson's disease had a significantly increased serum antibody level against HSV, but measles virus antibody levels were similar in both groups. Both in the Parkinson's group and in the control group, the levels of the total IgG in CSF were within normal limits and the CSF antibodies to HSV and measles virus paralleled the serum antibody titers relative to the total IgG serum-to-CSF ratios. This indicates no increased intrathecal antibody production in either group. In 48 patients with Parkinson's disease who were HLA-typed, no association of viral antibody levels with particular HLA antigens were noted. The findings suggest that HSV is not present within the central nervous system of the patients with Parkinson's disease. The increased HSV antibody level seen in Parkinson's disease patients may reflect a more general disturbance of the patients' immune functions.

The cerebrospinal fluid immunoglobulin G index as a diagnostic aid in multiple sclerosis: a Bayesian approach.

Having determined immunoglobulin G (IgG) and albumin concentrations in 1100 cerebrospinal fluid and serum samples, we calculated the IgG index. Likelihood ratios for multiple sclerosis were calculated by using a training set consisting of 100 patients with definite multiple sclerosis and one consisting of 97 patients suffering from diseases from which multiple sclerosis must be differentiated. Predictive values for multiple sclerosis, given different values for the IgG index, are given in a graphical representation of Bayes' theorem. We conclude that this approach increases the diagnostic usefulness of the IgG index for the diagnosis of multiple sclerosis.

Quantitative Determination of Immunoglobulins in CSF and Plasma of Chronic Schizophrenic Patients

Immunoglobulins, IgG, IgA and IgM were quantified in cerebrospinal fluid (CSF) and plasma from chronic schizophrenic patients and controls using an immunofluorescent antibody technique. A generalized reduction in immunoglobulin levels was observed in the schizophrenic patients compared with controls. While this study supports other reports of abnormal immune functioning in schizophrenia, it failed to replicate previous findings of elevations in CSF IgG and elevations in serum IgA. The aetiology and significance of these findings are hypothesized but remain elusive.