Oligoclonal IgG bands in cerebrospinal fluid in various neurological diseases

We studied the frequency of oligoclonal immunoglobulin G bands in the cerebrospinal fluid (CSF) of patients with various neurological diseases. We used a micromethod employing sodium dodecyl sulfate polyacrylamide gel electrophoresis that required only 50 μl of unconcentrated CSF. Oligoclonal bands were detected in the CSF of 95% of the patients with multiple sclerosis, 90% with subacute sclerosing panencephalitis, and 100% with herpes simplex encephalitis, but less frequently in other central nervous system infections. No oligoclonal bands were detected in the CSF of patients with Parkinson, Huntington, Creutzfeldt-Jakob, or herniated disc diseases. Bands were detected in some patients with Alzheimer disease, cerebrovascular accident, idiopathic vertigo, idiopathic seizures, amyotrophic lateral sclerosis, polyneuropathy, and central nervous system glioma. Patients with other conditions infrequently had positive bands. The determination of oligoclonal bands is a useful aid in the diagnosis of multiple sclerosis, subacute sclerosing panencephalitis, and herpes simplex encephalitis. The presence of oligoclonal bands indicates an immunological response but is not diagnostic for a particular condition.     

Oligoclonal IgG in multiple sclerosis and subacute sclerosing panencephalitis brains

IgG was obtained from multiple sclerosis (MS) and subacute sclerosing panencephalitis (SSPE) brain materials by elution at neutral and acid pH, and by freezing and thawing. Serum, cerebrospinal fluid (CSF), and brain eluates were compared by isoelectric focussing (IEF) with sensitive peroxidase-anti-IgG staining.In 3 MS cases, different plaques or regions of the same brain had IgG patterns with some common and some different bands. Pooled white matter eluates contained the summation of bands seen in individual plaques or regions. Comparison of serum, CSF, and neutral and acid brain eluate IgG patterns showed many common bands but also unique bands.In two SSPE cases, eluates from different regions of the same brain showed virtually identical IgG patterns. Comparisons of serum, CSF, and neutral and acid eluates of the same brain also showed a common pattern of bands.Similarities in IgG patterns of sera, CSF, and regional brain eluates, from single cases of SSPE, suggest a common response to the same antigen in all regions or compartments. Differences in IgG patterns of sera, CSF, pooled brain eluates, and plaques or regional eluates from single cases of MS, suggest: either that (a) all MS oligoclonal IgG is ‘nonsense’ antibody in terms of disease pathogenesis, or (b) much of the MS oligoclonal IgG is ‘nonsense’ antibody, present as part of a specific oligoclonal immune reaction.     

Oligoclonal IgG band patterns in inflammatory demyelinating human and mouse diseases

We evaluated oligoclonal IgG band (OCB) patterns obtained by analyzing paired cerebrospinal fluid (CSF) and serum samples of 77 patients with acute demyelinating encephalomyelitis (ADEM) and 411 patients with multiple sclerosis (MS). OCBs were searched with isoelectric focusing and capillary immunoblotting. CSF-restricted OCBs were found in 89% of MS patients and 10% of ADEM patients (p<0.0001). Identical serum and CSF OCBs ('mirror pattern'), or no OCBs, were detected in 10% of MS patients and 84% of ADEM patients (p<0.0001). OCBs were also analyzed in 27 mice with proteolipid protein-induced experimental autoimmune encephalomyelitis (EAE). In this animal model, the 'mirror pattern' was the most frequently detected pattern (74%), with the immunizing antigen being the main OCB target. These results indicate that CSF analysis can help differentiate between MS and ADEM and that, similarly to EAE, the 'mirror pattern' observed in ADEM accounts for a predominantly systemic immune activation.     

Oligoclonal IgG bands in the CSF of a patient with progressive familial myoclonus

An oligoclonal IgG pattern was found in the CSF of a patient who is known to suffer from progressive familial myoclonus. In view of this finding the possibility arises that immunological mechanisms participate in the etiopathogenesis of this disease.     

Oligoclonal IgG in the cerebrospinal fluid of guinea pigs with acute experimental allergic encephalomyelitis

The cerebrospinal fluid (CSF) of guinea pigs with experimental allergic encephalomyelitis was examined for the presence of oligoclonal IgG using polyacrylamide gel electrophoresis. Oligoclonal IgG (?2 bands) was seen in the CSF obtained from $\text{3}\text{4}$ animals with experimental allergic encephalomyelitis induced by myelin basic protein and $\text{2}\text{3}$ with spinal cord-induced disease. It was not seen in CSF of 3 non-sensitized, 4 adjuvant-sensitized and 7 liver-sensitized guinea pigs. Scanning of stained gels confirmed the oligoclonal pattern. The bands were found in the region of gels which bound [¹²⁵I]Staphylococcal Protein A. The data demonstrate that a non-infectious inflammatory reaction within the central nervous system can result in an oligoclonal IgG pattern in the CSF.     

Oligoclonal IgG bands in cerebrospinal fluid and serum during asymptomatic human immunodeficiency virus infection

Serum and cerebrospinal fluid (CSF) samples from asymptomatic patients seropositive for human immunodeficiency virus (HIV) showed frequent evidence of intrathecal IgG synthesis and oligoclonal IgG bands, with different isoelectric focusing patterns in serum and CSF; 2 of 7 had a CSF pleocytosis. The results suggest frequent, early, chronic central nervous system infection following HIV infection.     

Oligoclonal IgG bands synthesized in the central nervous system are present in rats with experimental autoimmune encephalomyelitis

OBJECTIVE: Oligoclonal bands (OBs) in electrophoresis of cerebrospinal fluid (CSF) are present in multiple sclerosis and here is investigated whether these also occur in experimental autoimmune encephalomyelitis (EAE). MATERIAL AND METHODS: Experimental autoimmune encephalomyelitis was induced in 42 DA rats after immunization with rat spinal chord homogenate and the occurrence of OBs were detected by electrophoresis of both sera and CSF. The relationship between disease symptoms, antibody response against myelin basic protein (MBP), myelin oligodendrocyte glycoprotein (MOG) and appearance of OBs was studied. RESULTS: Development of CSF-specific OB was found to occur, 6 weeks after immunization, in seven of 42 rats. OB was detected in rats with an antibody response against MBP, whereas as a role no such bands were present in rats with an antibody response against MOG. Initially severe disease symptoms were correlated to a concomitant intense oligoclonal antibody response. CONCLUSION: Cerebrospinal fluid-specific OB occurs in EAE. It is present in rats with an anti-MBP, but not in rats with an anti-MOG antibody response. A severe disease results in an intense oligoclonal antibody response, which might have an anti-inflammatory effect.     

Oligoclonal gammopathy in ataxia-telangiectasia

Summary In 2 cases of AT, M-components are present in the serum, emphasizing the complexity of the immunological anomalies of this disease. These M-components allow comparisons between hereditary neurological diseases and viral diseases with slow evolution.

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Zusammenfassung In 2 Fällen von Ataxia telangiectasia finden sich im Serum M-Komponenten. Dies bezeugt die Komplexheit der immunologischen Anomalien dieser Erkrankung. Diese M-Komponenten legen einen Vergleich zwischen den erblichen neurologischen Erkrankungen und Virusinfektionen mit langsamem Verlauf nahe.

     

Oligoclonal IgG and free chains in multiple sclerosis demonstrated by thin-layer polyacrylamide gel isoelectric focusing and immunofixation

A modified technique of isoelectric focusing on thin-layer polyacrylamide gel followed by immunofixation with monospecific antisera was used to identify individual cerebrospinal fluid (CSF) and serum proteins and to define the oligoclonal reaction observed in multiple sclerosis (MS). "Normal" IgG gave about 20 to 30 bands at pH 3.5 to 9.5, IgA about 10 bands at pH 3.5 to 6.4, beta-trace protein a smear at pH 3.5 to 8.5, and gamma-trace protein 1 or 2 bands at pH 8.0, 9.5 or both. Up to 11 oligoclonal IgG bands migrating between pH 6.5 and 9.5 were found in CSF from 26 of 27 consecutive patients with MS and also in 20 of the corresponding sera, although at lower numbers and concentrations. In 26 patients, 1 or more of the bands corresponding to normal polyclonal IgG were stronger in CSF than in serum. These data support the hypothesis that two colonies of lymphocytes are activated intrathecally, one of them synthesizing oligoclonal and the other polyclonal IgG. Up to 11 mostly faint bands of free light chains, predominantly of lambda type and migrating between pH 3.5 and 9.5, were found in 8 of 9 CSF specimens from patients with MS.     

脑脊液寡克隆区带、24小时鞘内IgG合成率及IgG指数在脑脊膜血管型神经梅毒诊断中的应用研究

目的 探讨脑脊液寡克隆区带、24 h鞘内IgG合成率及IgG指数在脑脊膜血管型神经梅毒诊断中的应 用价值。 方法 回顾性分析2014年6月-2019年6月于首都医科大学附属北京地坛医院神经内科连续住院的 脑脊膜血管型神经梅毒患者的临床资料,对脑脊液甲苯胺红不加热血清试验（toluidine red unheated serum test,TRUST）、寡克隆区带、24 h鞘内IgG合成率及IgG指数诊断脑脊膜血管型神经梅毒的阳性率 和假阴性率进行分析。 结果 研究共纳入确诊的脑脊膜血管型神经梅毒患者102例。脑脊液寡克隆区带、24 h鞘内IgG合 成率及IgG指数检查的阳性率分别为93.1%、93.1%和91.2%,均高于TRUST检查的阳性率（71.6%,均 P＜0.001）。脑脊液寡克隆区带、24 h鞘内IgG合成率及IgG指数检查的假阴性率分别为6.9%、6.9%及 8.8%,均低于TRUST检查（28.4%,均P＜0.001）。 结论 脑脊液寡克隆区带、24 h鞘内IgG合成率及IgG指数均可用于脑脊膜血管型神经梅毒的诊断, 且上述指标的敏感性和假阴性率均优于脑脊液TRUST检测。     

Oligoclonal IgG bands in Japanese patients with multiple sclerosis. A comparative study between isoelectric focusing with IgG immunofixation and high-resolution agarose gel electrophoresis

A low prevalence of oligoclonal IgG bands (OB) has been reported as a unique feature of Japanese multiple sclerosis (MS) as compared with Western MS. We compared the frequency of OB between isoelectric focusing (IEF) and agarose gel electrophoresis (AGE) in 59 Japanese patients with clinically definite MS [39 with conventional form of MS (CMS) and 20 with optic-spinal form of MS (OSMS)]. The frequency of IEF-OB in total MS was 54%, whereas that of AGE-OB was only 17%. When OSMS was excluded, the frequency increased to 77% by IEF, whereas it remained 23% by AGE. Our study strongly suggests that IEF is highly effective for detecting OB in Japanese MS patients.     

Oligoclonal IgG bands in cerebrospinal fluid. Principles for demonstration and interpretation based on findings in 1114 neurological patients

Unconcentrated cerebrospinal fluid (CSF) and serum samples from 1114 consecutive patients were examined for presence of oligoclonal IgG bands (OB) by agarose isoelectric focusing (AIF) followed by protein transfer to nitrocellulose membrane, immunolabeling, and avidinbiotin-peroxidase staining (avidin-biotin AIF). Oligoclonal bands were demonstrated in CSF from all 58 patients with multiple sclerosis (MS), eight of 29 with aseptic nervous system infections, and 9% of 1014 with other neurological disorders (OND) considered as noninflammatory at primary clinical evaluation. Comparative examination of all specimens in another laboratory by conventional AIF after concentration of CSF revealed lower frequencies of OB in all diagnostic groups. In addition to the high sensitivity of avidinbiotin AIF, which enables detection of OB by separation of 5 microL of unconcentrated CSF even when the CSF IgG level is around the lower normal range, the procedure also has optimal specificity since IgG exclusively is detected. Avidin-biotin AIF may be the method preferred for routine examination of CSF for OB. Demonstration of OB in CSF is valuable especially in MS, where, in contrast to diagnostic aids such as evoked potentials and neuro-imaging, it establishes inflammatory type of nervous system involvements. Oligoclonal IgG bands in CSF from patients with OND reflect intrathecal immune response and should lead to investigations of infectious etiology.     

Oligoclonal bands in unconcentrated CSF

Agarose gel electrophoresis (AGE) and agarose isoelectric focusing (AIEF) were performed on unconcentrated CSF from patients with multiple sclerosis and other neurological disorders. Electrophoretic profiles were examined after staining with silver. Oligoclonal distribution of immunoglobulins were observed in over 90% of patients with clinically definite multiple sclerosis and over half of all patients with possible or probable multiple sclerosis. Up to 20 samples could be simultaneously examined and required the use of only 2–20 μL of unconcentrated CSF containing 10–100 ng of total IgG. The entire procedure from sample application to completion of staining required less than 3 h. The techniques offered exquisite resolution of abnormal immunoglobulin bands and permitted distinction of normal from abnormal CSF readily.     

Oligoclonal bands in cerebrospinal fluid: a comparative study of isoelectric focusing, agarose gel electrophoresis and IgG index

OBJECTIVE: To compare the sensitivity and specificity of isoelectric focusing (IEF) with immunofixation, agarose gel electrophoresis (AGE) and the IgG index in detecting intrathecally synthesized IgG in multiple sclerosis (MS) and in other nervous system disorders. MATERIALS AND METHODS: Cerebrospinal fluid (CSF) and serum from 147 patients with various nervous system diseases, 20 of whom had MS, were compared with IEF, AGE and the IgG index. RESULTS: CSF-restricted oligoclonal bands (OCB) were found in 20 of 20 patients with MS using IEF and in 9 of 20 using AGE. OCB were found in 12 patients with other nervous system disorders (OND) using IEF and 4 using AGE. The mean IgG index was 0.50 in OND and 0.96 in MS (P< 0.0001). Of 20 MS patients, 9 had an IgG index above the defined cut-off value of 0.72. CONCLUSIONS: IEF is about twice as sensitive as AGE in detecting OCB in MS. IEF is also far superior to the IgG index in determining intrathecal IgG synthesis.     

The occurrence of oligoclonal IgG in tears from patients with MS and systemic immune disorders

Using isoelectric focusing (IEF) and immunoperoxidase staining of proteins transferred to nitrocellulose membranes, we have examined the IgG band pattern in tears and matched serum and CSF specimens of 28 patients with MS, 4 patients with optic neuritis (ON), 30 individuals with systemic, inflammatory, or other neurologic diseases, and 5 patients with tension headache. We found no evidence of positive oligoclonal IgG in tears in any MS or ON patients, while 10 out of 16 cases with systemic immune disorders or infections of the CNS had positive tear oligoclonal bands. We are thus not able to support the hypothesis that tears from MS patients reveal abnormalities in their humoral immune response.     

Oligoclonal "fingerprint" of CSF IgG in multiple sclerosis patients is not modified following intrathecal administration of natural beta-interferon.

The IgG pattern in CSF was studied in 11 patients with multiple sclerosis who exhibited an oligoclonal banding upon thin-layer polyacrylamide gel isoelectric focusing followed by silver stain of unconcentrated CSF. Each patient received beta-interferon intrathecally during a 2 month period. No modification was observed over a 6 month period. In addition, the oligoclonal pattern was remarkably unique for each individual representing a typical "fingerprint" which allowed the identification of any single CSF.     

Oligoclonal IgG bands in patients with HTLV-I associated myelopathy--detection by agarose isoelectric focusing, transfer to cellulose nitrate and immunoperoxidase staining

The patient with HTLV-I associated myelopathy (HAM) shows a quite uniform clinical picture characterized by slowly progressive spastic paraparesis, slight sensory disturbances and urinary frequency, and the pathogenetic relationship between spastic paraparesis and HTLV-I was established. Since then, the role of the virus in causing myelopathy has drawn increasing attention. However, we have little information about cerebrospinal fluid (CSF) abnormalities in patients with HAM. Analysis of CSF oligoclonal bands (OB) in 22 patients with HAM was reported. All of 22 patients had typical clinical signs and symptoms of HAM with high titers of anti-HTLV-I antibodies in the serum by particle agglutination method. And these antibodies against HTLV-I were confirmed by enzyme-linked immunosorbent assay and western blot. Detection or characterization of CSF OB was done by high resolution agarose gel (HARG) electrophoresis with silver staining and immunofixation method with immunostaining. Other method for detection OB was by agarose isoelectric focusing (IEF), transfer to cellulose nitrate and immunoperoxidase staining (Olsson, 1984). CSF OB was detected in 13 of 22 patients with HAM by the method of immunofixation, using HRAG. All of CSF OB reacted with peroxidase conjugated goat anti-human IgG serum. More than 3 oligoclonal bands were not detected in HRAG electrophoresis. However, CSF OB was detected in all of 22 patients by the method of Olsson (IEF, in agarose, double-antibody peroxidase labelling and avidin-biotin amplification). The majority of patients with HAM had at least 5 or more OB in the region between pH 6.8 and 9.5.(ABSTRACT TRUNCATED AT 250 WORDS)