Cerebrospinal fluid oligoclonal IgG bands in multiple sclerosis: what does it mean?

We assessed the frequency of cerebrospinal fluid (CSF) restricted oligoclonal IgG bands (IgG-OCB) in Portuguese multiple sclerosis (MS) patients and its relationship with outcome. Paired CSF/serum samples of 406 patients with neurological disorders were submitted to isoelectric focusing with immunodetection of IgG. Ninety-two patients had definite MS; non-MS cases were assembled in groups inflammatory/infectious diseases (ID, n=141) and other/controls (OD, n=173). We found in the MS group: mean duration, 38.9 months; clinically isolated syndromes, 24%; relapsing/remitting course (RR), 65%; in RR patients the mean EDSS was 2.1 and the mean index of progression was 0.31. Positive patterns significantly predominated in MS (82.6%; ID, 40.4%; OD, 3.5%). The sensitivity and the specificity of positive IgG-OCB for MS diagnosis was 82.6% and 79.9%, respectively. The sole statistically significant difference in the MS group was the lower progression index observed in negative cases. We conclude that the frequency of positive IgG-OCB patterns in our MS patients fits most values reported in the literature, and that negative results indicate benign disease.

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Multiple sclerosis immunopathic trait and HLA-DR(2)15 as independent risk factors in multiple sclerosis

Multiple Sclerosis Journal ◽

10.1177/1352458506070264 ◽

2007 ◽

Vol 13 (4) ◽

pp. 441-445 ◽

Cited By ~ 5

Author(s):

M. Callander ◽

S. Haghighi ◽

A.-M. Landtblom ◽

C.E. Ahlgren ◽

S.I. Nilsson ◽

...

Keyword(s):

Risk Factors ◽

Multiple Sclerosis ◽

Cerebrospinal Fluid ◽

Susceptibility Gene ◽

Hla Dr ◽

Healthy Siblings ◽

Independent Risk Factors ◽

Oligoclonal Igg ◽

Hla Haplotypes ◽

Oligoclonal Igg Bands

We analysed HLA haplotypes in pairs of 78 sporadic multiple sclerosis (MS) patients and 78 healthy siblings. The presence of 2 oligoclonal IgG bands, detected by immunoblotting of the cerebrospinal fluid in healthy siblings, has previously been defined as MS immunopathic trait (MSIT), based on a cut-off derived from healthy unrelated volunteers. The frequency of MSIT was 17.9% (n=14/78 siblings). The HLA-DR(15)2 allelle was present in 21.4% (n=3/14) of the siblings with MSIT, in 40.6% (n =26/64) of the siblings without MSIT, and in 59% (n =46/78) of the patients with clinically-definite (CD) MS. The distribution of zero, one or two HLA-DR(2)15 alleles was significantly skewed towards a lower allelle count in the siblings with MSIT compared with the group of unrelated siblings with MS (P=0.002), and also lower than their related siblings with MS (P=0.1). These results suggest that the MS susceptibility gene, HLA-DR(2)15 type, does not induce MSIT, and conceivably these are two separate risk factors in the development of MS. The effect of HLA-DR(2)15 and MSIT in sporadic MS appears to be synergistic. Multiple Sclerosis 2007; 13: 441-445. http://msj.sagepub.com

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Candidate antigens specifically detected by cerebrospinal fluid-IgG in oligoclonal IgG bands-positive multiple sclerosis patients

PROTEOMICS - CLINICAL APPLICATIONS ◽

10.1002/prca.200700182 ◽

2007 ◽

Vol 1 (7) ◽

pp. 681-687 ◽

Cited By ~ 3

Author(s):

Masashi Nakamura ◽

Atsuo Kuramasu ◽

Ichiro Nakashima ◽

Kazuo Fujihara ◽

Yasuto Itoyama

Keyword(s):

Multiple Sclerosis ◽

Cerebrospinal Fluid ◽

Positive Multiple ◽

Oligoclonal Igg ◽

Multiple Sclerosis Patients ◽

Oligoclonal Igg Bands

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Cerebrospinal Fluid Findings in 541 Patients With Clinically Isolated Syndrome and Multiple Sclerosis: A Monocentric Study

Frontiers in Immunology ◽

10.3389/fimmu.2021.675307 ◽

2021 ◽

Vol 12 ◽

Author(s):

Klaus Berek ◽

Gabriel Bsteh ◽

Michael Auer ◽

Franziska Di Pauli ◽

Anne Zinganell ◽

...

Keyword(s):

Multiple Sclerosis ◽

Cerebrospinal Fluid ◽

White Blood Cells ◽

Clinically Isolated Syndrome ◽

The Novel ◽

Barrier Dysfunction ◽

Csf Pleocytosis ◽

Oligoclonal Igg ◽

Wbc Count ◽

Oligoclonal Igg Bands

BackgroundReports on typical routine cerebrospinal fluid (CSF) findings are outdated owing to novel reference limits (RL) and revised diagnostic criteria of Multiple Sclerosis (MS).ObjectiveTo assess routine CSF parameters in MS patients and the frequency of pathologic findings by applying novel RL.MethodsCSF white blood cells (WBC), CSF total protein (CSF-TP), CSF/serum albumin quotient (Qalb), intrathecal synthesis of immunoglobulins (Ig) A, M and G, oligoclonal IgG bands (OCB) were determined in patients with clinically isolated syndrome (CIS) and MS.ResultsOf 541 patients 54% showed CSF pleocytosis with a WBC count up to 40/μl. CSF cytology revealed lymphocytes, monocytes and neutrophils in 99%, 41% and 9% of patients. CSF-TP and Qalb were increased in 19% and 7% applying age-corrected RL as opposed to 34% and 26% with conventional RL. Quantitative intrathecal IgG, IgA and IgM synthesis were present in 65%, 14% and 21%; OCB in 95% of patients. WBC were higher in relapsing than progressive MS and predicted, together with monocytes, the conversion from CIS to clinically definite MS. Intrathecal IgG fraction was highest in secondary progressive MS.ConclusionsCSF profile in MS varies across disease courses. Blood-CSF-barrier dysfunction and intrathecal IgA/IgM synthesis are less frequent when the novel RL are applied.

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Silver staining of unconcentrated cerebrospinal fluid in agarose gel (Panagel) electrophoresis.

Clinical Chemistry ◽

10.1093/clinchem/30.5.735 ◽

1984 ◽

Vol 30 (5) ◽

pp. 735-736 ◽

Cited By ~ 9

Author(s):

P D Mehta ◽

S P Mehta ◽

B A Patrick

Keyword(s):

Multiple Sclerosis ◽

Cerebrospinal Fluid ◽

Silver Staining ◽

Clinical Laboratory ◽

Neurological Diseases ◽

Agarose Gel ◽

Oligoclonal Igg ◽

Multiple Sclerosis Patients ◽

Coomassie Brilliant ◽

Oligoclonal Igg Bands

Abstract We subjected cerebrospinal fluid (CSF) from 20 patients with multiple sclerosis and 20 patients with other neurological diseases to agarose gel ( Panagel ) electrophoresis followed by staining with silver. Ten microliters of unconcentrated CSF from multiple sclerosis patients containing 0.4 to 0.8 microgram of immunoglobulin G was found to be optimum for detection of oligoclonal IgG bands, so identified by immunofixation. The band patterns for unconcentrated CSF stained with silver were almost identical to those for the same CSF concentrated 40-fold and stained with Coomassie Brilliant Blue. Silver staining thus enables the clinical laboratory to electrophorese unconcentrated CSF on commercially prepared ( Panagel ) plates.

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Prevalence of cerebrospinal fluid oligoclonal IgG bands in Greek patients with clinically isolated syndrome and multiple sclerosis

Clinical Neurology and Neurosurgery ◽

10.1016/j.clineuro.2013.07.026 ◽

2013 ◽

Vol 115 (10) ◽

pp. 2094-2098 ◽

Cited By ~ 10

Author(s):

E. Andreadou ◽

S. Chatzipanagiotou ◽

V.C. Constantinides ◽

A. Rombos ◽

E. Stamboulis ◽

...

Keyword(s):

Multiple Sclerosis ◽

Cerebrospinal Fluid ◽

Clinically Isolated Syndrome ◽

Oligoclonal Igg ◽

Oligoclonal Igg Bands

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Latitude and HLA-DRB1 alleles independently affect the emergence of cerebrospinal fluid IgG abnormality in multiple sclerosis

Multiple Sclerosis Journal ◽

10.1177/1352458514560924 ◽

2015 ◽

Vol 21 (9) ◽

pp. 1112-1120 ◽

Cited By ~ 8

Author(s):

Masaaki Niino ◽

Shinya Sato ◽

Toshiyuki Fukazawa ◽

Satoshi Yoshimura ◽

Shin Hisahara ◽

...

Keyword(s):

Multiple Sclerosis ◽

Cerebrospinal Fluid ◽

Regression Analysis ◽

Japanese Patients ◽

Geographic Region ◽

Igg Index ◽

Oligoclonal Igg ◽

Oligoclonal Igg Bands ◽

Csf Findings ◽

Northern Japan

Background: It is unclear whether the prevalence of oligoclonal IgG bands (OCBs) in multiple sclerosis (MS) is different between northern and southern regions of Asia. Objective: This study aimed to compare the prevalence of OCBs and positive cerebrospinal fluid (CSF) findings between northern and southern regions of Japan and to investigate the association of these CSF findings with HLA-DRB1 alleles. Methods: The study included 180 MS patients from Hokkaido (northern Japan) and 184 patients from Kyushu (southern Japan). The IgG index was defined as increased if it was >0.658. Presence of CSF OCBs and/or increased IgG index was defined as positive CSF findings. Results: Positive CSF findings and OCB positivity were significantly higher in MS patients from Hokkaido than in those from Kyushu ( p < 0.0001 for both). Logistic regression analysis revealed that after adjusting for covariates that can be related to abnormal CSF IgG production, the geographic region (Hokkaido) showed odds ratios (ORs) of 4.08 and 2.57, whereas the HLA-DRB1*04:05 allele showed ORs of 0.36 and 0.30 for positive CSF findings and OCB positivity, respectively. Conclusions: The results indicate that latitude and HLA-DRB1 alleles independently affect the emergence of CSF IgG abnormalities in Japanese patients with MS.

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Multiple sclerosis patients lacking oligoclonal bands in the cerebrospinal fluid are less likely to develop neutralizing antibodies against interferon beta

Multiple Sclerosis Journal ◽

10.1177/1352458510373112 ◽

2010 ◽

Vol 16 (7) ◽

pp. 796-800 ◽

Cited By ~ 15

Author(s):

M. Lundkvist ◽

E. Greiner ◽

J. Hillert ◽

A. Fogdell-Hahn

Keyword(s):

Multiple Sclerosis ◽

Cerebrospinal Fluid ◽

Neutralizing Antibodies ◽

Neutralizing Antibody ◽

Oligoclonal Bands ◽

Distinct Subgroup ◽

Oligoclonal Igg ◽

Multiple Sclerosis Patients ◽

Genetically Determined ◽

Oligoclonal Igg Bands

Multiple sclerosis patients without cerebrospinal fluid oligoclonal IgG bands have been proposed to constitute an immunogenetically distinct subgroup of multiple sclerosis that may also differ in terms of prognosis. A proportion of patients with multiple sclerosis receiving IFNβ develop neutralizing antibodies, which interfere with treatment efficacy. Evidence suggests that the likelihood of developing neutralizing antibodies is partly genetically determined. Here, we hypothesized that absence of oligoclonal IgG bands reflects a property of B-cell responses in oligoclonal IgG band-negative patients characterized by a lessened propensity to develop neutralizing antibodies. We aimed to compare the development of neutralizing antibodies against IFNβ between oligoclonal IgG band-negative and oligoclonal IgG band-positive multiple sclerosis patients. Treatment, oligoclonal IgG band and neutralizing antibody information was obtained for 2219 patients from the Swedish multiple sclerosis registry and the Swedish neutralizing antibody registry. Additional data on genotype was available for 532 patients. A correlation was found between oligoclonal IgG band negativity and neutralizing antibody negativity ( p = 0.02). This difference was confined to neutralizing antibodies against IFNβ-1a, since oligoclonal IgG band-negative patients were, to a lesser extent, neutralizing antibody positive compared with oligoclonal IgG band-positive patients if treated with IFNβ-1a (12% vs. 23%; p = 0.005). No difference was observed for IFNβ-1b-treated patients (44% vs. 46%). We propose that oligoclonal IgG band-negative patients differ immunologically from oligoclonal IgG band-positive patients, potentially influenced by distinct HLA-DRB1 alleles.

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Isoelectric Focusing in an Immobilized pH Gradient for the Detection of Intrathecal IgG in Cerebrospinal Fluid: Sensitivity and Specificity for the Diagnosis of Multiple Sclerosis

Annals of Clinical Biochemistry International Journal of Laboratory Medicine ◽

10.1177/000456329303000509 ◽

1993 ◽

Vol 30 (5) ◽

pp. 463-468 ◽

Cited By ~ 6

Author(s):

G N Cowdrey ◽

P J Tasker ◽

B J Gould ◽

M Rice-Oxley ◽

G B Firth

Keyword(s):

Multiple Sclerosis ◽

Cerebrospinal Fluid ◽

Sensitivity And Specificity ◽

Isoelectric Focusing ◽

High Specificity ◽

Ph Gradient ◽

Alkaline Ph ◽

Oligoclonal Igg ◽

Very High ◽

Oligoclonal Igg Bands

Cerebrospinal fluid and serum from 192 patients was analysed for the presence of intrathecally synthesized oligoclonal IgG bands using isoelectric focusing in an immobilized pH gradient pH7–10. The sensitivity of this method for the diagnosis of multiple sclerosis (MS) was 95% (21 of 22), or 75% if patients with suspected MS were included. The specificity for the diagnosis of MS was 98%, or 96% if the suspected MS patients were included. The very high specificity may be because the intrathecally synthesized oligoclonal IgG associated with MS is more alkaline than IgG from serum and is better detected in an immobilized alkaline pH gradient.

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