IgM In Cerebrospinal Fluid Research Articles

The sheep (Ovis aries) as an experimental model for African trypanosomiasis. II. Biological study.

Sheep that have been experimentally infected with a strain of Trypanosoma brucei brucei reproduce the clinical symptomatology of human African trypanosomiasis. We measured two biochemical parameters which are altered during the infection; total serum and cerebrospinal fluid (CSF) proteins, and the time of appearance and levels of IgM in both serum and CSF. Serum protein levels were considerably raised (up to 90 gl-1), although in CSF the levels were always less than 1 gl-1. The ratio of serum albumin to globulins fell to a value of 0.40 during the course of the disease. Electrophoresis of CSF proteins demonstrated the appearance of polyclonal immunoglobulins. Plasma IgM levels rose to ten times normal values, and after the sixth week IgMs made up 10% of total CSF protein content. Specific antibodies were detected, by both indirect immunofluorescence and an ELISA technique, within two weeks after infection in the blood and after four weeks in the CSF.

Cerebrospinal Fluid Immunoglobulins and 2-Microglobulin in Lymphoproliferative and Other Neoplastic Diseases of the Central Nervous System

Humoral immune aberrations may occur in the cerebrospinal fluid (CSF) of patients with lymphoproliferative and other neoplastic diseases infiltrating the central nervous system (CNS). Such aberrations may be of diagnostic importance. We therefore studied CSF and serum from 47 patients with lymphoproliferative diseases and from 16 patients with various nonlymphoid neoplasias; 17 patients and 12 patients, respectively, had neoplastic CNS involvement. Elevated CSF IgM index and oligoclonal IgG bands in CSF and serum were commonly found, especially in patients with CNS involvement. Cerebrospinal fluid IgG and IgA indexes were usually normal. Increased CSF to serum albumin ratio, reflecting blood-brain barrier dysfunction, and increased CSF beta 2-microglobulin concentration were most common in patients with CNS involvement. The results indicate that neoplastic CNS disease should be borne in mind when CSF humoral immune aberrations are found.

Protein transfer at the blood cerebrospinal fluid barrier and the quantitation of the humoral immune response within the central nervous system

The cerebrospinal fluid (CSF)/serum concentration quotients of albumin and the immunoglobulins G, A and M have been determined for 396 patients with a normal blood CSF barrier function or a pure barrier impairment without a humoral immune response within the central nervous system. The ratios between the concentration quotients of the three immunoglobulins and that of albumin increase in a nonlinear fashion with progressive impairments of the blood CSF barrier, i.e. the molecular size dependent discrimination of the protein transfer (‘selectivity’) decreases. The upper reference values of the concentration quotients for the whole range of passive transfer comply with the hyperbolic function: Q( IgX) = a b √ Q(Alb) 2 + b 2 − c with different constants a b , b 2, c for IgG (0.8, 15 × 10 −6, 1.8 × 10 −3), IgA (0.72, 80 × 10 −6, 5.1 × 10 −3) and IgM (0.65, 150 × 10 −6, 7.5 × 10 −3). With these discriminatory functions the locally synthesized fractions IgX(loc) of IgG, IgA and IgM in CSF can be calculated by the general formula: IgX(loc) = [Q( IgX) − a b √Q( Alb) 2 + b 2 + c] . IgX(Ser).

Viral IgM antibodies in serum and cerebrospinal fluid in patients with multiple sclerosis and controls.

Serum and cerebrospinal fluid (CSF) from 28 patients with multiple sclerosis (MS), 14 with other neurological diseases (OND) and 31 control subjects with tension headache were analysed for presence of IgM antibodies against measles, mumps and varicellae zoster by a specific enzyme-linked immunosorbent assay (ELISA). This technique excluded false positive reaction due to possible presence of rheumatoid factor. Twelve of the 28 patients with MS had IgM antibodies in serum and 4 in CSF, the latter always being accompanied by presence of corresponding IgM antibodies in serum. Six patients had mumps specific IgM, 5 had measles specific IgM and 3 varicellae specific IgM. In 2 patients, viral IgM antibodies were demonstrated in serum against 2 different viruses. Among the 14 OND patients, one with Wilson's disease had demonstrable serum IgM varicellae antibodies and one with radicultis had elevated serum and CSF measles and varicellae IgM antibodies. Among 31 controls, 2 had IgM antibodies in serum, one against varicellae and one against mumps. No correlations were found between viral IgM antibodies and CSF IgM index, serum IgM levels or blood-brain barrier state. Our data show that MS may be accompanied by a systemic IgM response against the 3 viruses tested, occasionally against 2 of the 3 different viruses simultaneously. The occurrence in MS of virus-specific IgM may be a reflection of viral reactivation and/or polyclonal B cell activation.

Immunoglobulin abnormalities in the cerebrospinal fluid during bacterial meningitis

11 patients with bacterial meningitis, examined during the course of the disease for immunoglobulin (Ig) abnormalities in the cerebrospinal fluid (CSF), all had an increased CSF IgM index equal to (CSF/serum IgM):(CSF/serum albumin), indicating intrathecal IgM production. Seven patients had a slightly increased CSF IgG index, and 7 a slightly increased IgA index. Six of the 11 patients had an increased IgM index in the presence of normal indices for IgG and IgA. Follow-up revealed the return of these values to normal. Four patients had identical oligoclonal IgG bands in the CSF and serum, probably representing a systemic immune response, but in only one case were oligoclonal bands suggestive of intrathecal IgG production found. No oligoclonal IgA response was demonstrable in the 4 patients examined. Antigen-immunofixation or antigen-absorption studies revealed evidence of a specific, intrathecal IgG antibody response in only 2 patients, while a search for IgG antibodies against aetiologically unrelated bacterial and viral antigens was negative. With the exception of IgM production, therefore, a humoral intrathecal immune response is less common in bacterial than in aseptic meningitis.

Immunoglobulin abnormalities in cerebrospinal fluid and blood over the course of lymphocytic meningoradiculitis (Bannwarth's syndrome).

The conditions of 5 patients with untreated lymphocytic meningoradiculitis (Bannwarth's syndrome, probably equivalent to Lyme disease) with serologically confirmed infection resulting from Borrelia spirochetes were followed with repetitive lumbar punctures up to 221 days after the onset of symptoms. Using a protein A plaque assay, high numbers of IgG-, IgM-, and IgA-producing cells were found in the cerebrospinal fluid (CSF), whereas there were mostly normal numbers of immunoglobulin-producing cells in peripheral blood. A markedly increased CSF IgM index and an elevated IgG index were observed in all patients during the early phase, reflecting production of these immunoglobulins within the central nervous system. All patients had oligoclonal IgG bands in the CSF that persisted during follow-up; in the 2 patients tested, the bands contained Borrelia antibodies. Most serum immunoglobulin concentrations were normal and in only 1 patient was it possible to detect in serum some of the oligoclonal IgG bands present in CSF. Declining numbers of CSF cells producing immunoglobulin and decreasing immunoglobulin index values were observed during follow-up, but 3 patients had an elevated CSF IgM index in the presence of normal IgG and IgA indices when examined during the later phases of disease. An intense and prolonged IgM response within the central nervous system seems to be a characteristic of the disease.

Association of cerebrospinal fluid IgM index with central nervous system involvement in Behçet's disease.

Immunoglobulin (IgM, IgA, and IgG) and albumin values were determined in 12 patients who had signs and symptoms of central nervous system involvement attributable to Behçet's disease. Only the cerebrospinal fluid IgM index, which was significantly elevated in patients with active neuro-Behçet's syndrome, was found to decrease when the neurologic manifestations of the disease had disappeared. This indicates that determination of this index may be of help in the evaluation of central nervous system disease activity in neuro-Behçet's syndrome.

Detection of viral antigens in cerebrospinal fluid of rabbits with experimental herpes simplex virus type 1 encephalitis.

We investigated several methods for the rapid diagnosis of herpes simplex virus induced encephalitis in a rabbit model. The corneas of twenty-two rabbits were infected with herpes simplex virus type 1 (HSV-1) and diagnosis of Herpes encephalitis was made by virus isolation, immunofluorescent and peroxidase staining of brain biopsies, demonstration of anti-HSV IgM in cerebrospinal fluid (CSF) and by an indirect enzyme-linked immunosorbent assay (ELISA), designed for detection of viral antigens. With the last method we were able to demonstrate viral antigens in cerebrospinal fluid six days post infection, before clinical signs of encephalitis appeared. In three rabbits this was before anti-HSV IgM appeared in the CSF. Virus was isolated from brain samples of 67 per cent of the animals which died from Herpes encephalitis. Nine rabbits received cortisone before infection, resulting in markedly lower antibody titers and a higher lethality, 77 per cent, as compared to 46 per cent in nontreated rabbits. For rapid diagnosis of Herpes encephalitis in rabbits, demonstration of herpes simplex virus antigens in CSF by means of an indirect ELISA is superior to the other methods investigated.

Field trial of a Japanese encephalitis diagnostic kit.

Serum and cerebrospinal fluid (CSF) obtained from patients in rural Thailand during an encephalitis epidemic were assayed with a Japanese encephalitis rapid diagnosis kit. Japanese encephalitis was diagnosed by detection of virus-specific IgM (JEV IgM) in CSF (1:10 dilution) or serum (1:100 dilution) with an antibody capture enzyme-linked immunosorbent assay. Specimens were assayed immediately on site at the provincial hospital and scored by visual examination within 4 h. Each specimen was retested carefully later to accurately determine its activity (units) at a single screening dilution; each was tested also at serial dilutions to determine its end-point titer. On-site kit results showed close agreement with subsequent laboratory results for detection and quantitation of JEV IgM and JEV IgG in either serum or CSF. Using the kit on site, admission CSF from 35 (73%) of 48 laboratory-proven JEV-infected patients were scored as definitely positive for JEV IgM, while all 17 CSF specimens from non-JEV infected patients were read as negative (sensitivity 73%, specificity 100%). A rapid and early diagnosis of acute Japanese encephalitis can be accomplished almost anywhere.

Fatal outcome in Japanese encephalitis.

Forty-nine consecutive patients with laboratory-confirmed acute Japanese encephalitis were studied to identify risk factors present at hospital admission which were associated with a fatal outcome. Sixteen patients (33%) died. The following constellation of findings correlated with a fatal outcome: infectious virus in cerebrospinal fluid (CSF), low levels of Japanese encephalitis virus-specific IgG and IgM in both CSF and serum, and a severely depressed sensorium. Age, sex, days ill before admission, distance from home to the hospital, past medical history, CSF protein content, and CSF leukocyte count were not significant risk factors. Among patients hospitalized for acute Japanese encephalitis, a vigorous virus-specific immunoglobulin response, both systemically and locally within the central nervous system, is a good marker for survival, and may be an inherently important factor in recovery from illness.

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.

Cerebrospinal fluid IgM, IgA, and IgG indexes in systemic lupus erythematosus. Their use as estimates of central nervous system disease activity

Cerebrospinal fluid IgM, IgA, and IgG indexes in systemic lupus erythematosus. Their use as estimates of central nervous system disease activity

A sensitive and simple method for determination of IgM in cerebrospinal fluid by a solid-phase enzyme-immunoassay: Comparison of two different methods

A sensitive and simple solid-phase enzyme-immunoassay for quantitative determination of IgM in cerebrospinal fluid has been developed. This method is based on a sandwich technique and is much more sensitive than the competition enzyme-immunoassay which we described previously. The IgM values obtained by this sandwich technique were well correlated with those by the competition technique. This new method is considered to be more suitable for the estimation of IgM in cerebrospinal fluid because of its simplicity and good sensitivity.

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.

Estimation of IgM in cerebrospinal fluid by enzyme immunoassay

A solid-phase enzyme immunoassay (EIA) is described for measuring concentrations of IgM in cerebrospinal fluid (CSF), Commercially available antiserum and standard are used. This assay in which 1 ng of IgM can readily be measured offers a reliable ~ternative to other currently available procedures. Reference intervals for the IgM concentration and the IgM index have been determined for a group of 125 patients with normal concentrations of albumin, IgG and total protein in the CSF, and normal concentrations of albumin, IgG and IgM in the corresponding sera.

Cerebrospinal fluid findings in mycoplasma pneumoniae infections with neurological complications.

The cerebrospinal fluid (CSF) findings of 16 patients with mycoplasma pneumoniae infections and different neurologic complications are presented. In acute meningitis there was predominantly a mononuclear cell reaction remitting in accordance with the improvement of the clinical symptoms. An early switch from IgM to IgG was observed. In cranial nerve neuritis and radiculitis in the beginning complement factors were decreased. Far beyond the clinical remission IgM and cell count were elevated. In Guillain-Barré-syndrome no IgM but increased IgG levels were detectable. In all patients both CSF IgM and IgG markedly exceeded the corresponding serum values. The possibility that different pathogenetic mechanisms are underlying these phenomena depending on the actual state of the hosts' immunity is discussed.

Immune complexes in serum and in cerebrospinal fluid in African trypanosomiasis. Correlation with polyclonal B cell activation and with intracerebral immunoglobulin synthesis.

The possible occurrence of immune complexes (IC) in serum and in cerebrospinal fluid (CSF) has been studied in 36 patients with African trypanosomiasis (Trypanosoma brucei gambiense). In serum, very high levels of IC were detectable by the (125)I-C1q-binding and by the conglutinin-binding assays with positive results in 94 and 87%, respectively, of untreated patients. Circulating IC were found in both early and late stages of the disease, without significant quantitative differences; their size was 15-25S. There was a significant negative correlation between C3 values and C1qBA. Our studies suggest that circulating IC occurring during trypanosomiasis may be the expression of a polyclonal B cell activation. Indeed, there was a significant correlation (P < 0.001) between the levels of circulating IC and either the levels of IgM (mean value 12.5+/-7.2 mg/ml) or with the levels of rheumatoid factor-like antiimmunoglobulin antibodies that were detected by solid phase radioimmunoassay in 74% of the patients.IC were detected in 31 of 35 CSF samples, with a marked elevation in patients with definite involvement of the central nervous system as compared with earlier stages of sleeping sickness. The occurrence of IC in CSF was not related to an impairment of the blood-brain barrier as shown by analysis of CSF/serum albumin ratios. The level of IC in CSF did not correlate with the serum level and, therefore, circulating IC do not appear to cross efficiently an unimpaired blood-brain barrier. The analysis of IgG, IgM, and albumin concentrations in serum and CSF demonstrates a marked intracerebral immunoglobulin synthesis in patients with manifestations of meningoencephalitis. There was a correlation between CSF-C1q binding assay and this local IgG synthesis. These data are consistent with a local formation of IC in CSF in patients with active meningoencephalitis. The results obtained in eight patients followed during therapy suggest that the presence of IC in CSF may be an indicator of a continuing central nervous system disease and that the quantitation of CSF-IC may be useful for monitoring patient care.

Immunoglobulins in cerebrospinal fluid: Enzyme-immunoassay

Using an enzyme-immunoassay (EIA) technique we established control values for IgA and IgM in cerebrospinal fluid (CSF). These values, together with IgG values determined by single radial immunodiffusion (SRID) technique, showed significant positive correlations with CSF total protein values. The CSF IgA and IgM levels were related to corresponding levels determined in serum. In addition, the values for all 3 immunoglobulin classes in CSF as well as CSF total protein values showed positive correlation with age of subjects, and IgG% and IgA% increased with age. This new EIA procedure can be completed within 24 h and is sensitive enough for determining all 3 immunoglobulin classes using a small amount (100 μl or less) of native CSF.

Cerebrospinal fluid immunoglobulins in children.

Cerebrospinal fluid (CSF) immunoglobulins were measured in 62 normal children, in 9 children with purulent meningitis, and in 10 children with presumptive viral meningitis. The mean values in normal children were IgA 0, IgM 0, and IgG 0.84 +/- 1.4 mg/100 ml (+/- SD). The mean levels of all CSF immunoglobulins were raised in acute bacterial meningitis and were significantly greater than the levels found in viral meningitis. CSF IgM was 0.16 +/- 0.5 mg/100 ml in viral meningitis compared with 2.64 +/- 2.06 mg/100 ml in bacterial meningitis (P less than 0.01). However, these values overlapped to a considerable extent and, generally, measurement of CSF immunoglobulins did not enhance diagnostic accuracy in this group of children.

Estimation of IgM in cerebrospinal fluid by fluoroimmunoassay

Estimation of IgM in cerebrospinal fluid by fluoroimmunoassay