Bands In Cerebrospinal Fluid Research Articles

Brain-specific Proteins Decline in the Cerebrospinal Fluid of Humans with Huntington Disease

We integrated five sets of proteomics data profiling the constituents of cerebrospinal fluid (CSF) derived from Huntington disease (HD)-affected and -unaffected individuals with genomics data profiling various human and mouse tissues, including the human HD brain. Based on an integrated analysis, we found that brain-specific proteins are 1.8 times more likely to be observed in CSF than in plasma, that brain-specific proteins tend to decrease in HD CSF compared with unaffected CSF, and that 81% of brain-specific proteins have quantitative changes concordant with transcriptional changes identified in different regions of HD brain. The proteins found to increase in HD CSF tend to be liver-associated. These protein changes are consistent with neurodegeneration, microgliosis, and astrocytosis known to occur in HD. We also discuss concordance between laboratories and find that ratios of individual proteins can vary greatly, but the overall trends with respect to brain or liver specificity were consistent. Concordance is highest between the two laboratories observing the largest numbers of proteins.

Lipid-specific immunoglobulin M in CSF predicts adverse long-term outcome in multiple sclerosis

Background and Objective The presence of lipid-specific immunoglobulin M bands in the cerebrospinal fluid (CSF) predicts an aggressive course in patients with relapsing–remitting multiple sclerosis (MS) during early stages of the disease. This study examined whether it is also a predictor of long-term prognosis in MS. Methods Eighty-one patients with MS and 22 headache controls were analyzed for anti-lipid IgM reactivity in CSF samples. The correlation between the presence of lipid-specific immunoglobulin M bands in CSF and disease progression was assessed in patients with MS who had been followed longitudinally for, on average, more than 11 years. Results Lipid-specific immunoglobulin M bands were detected in the CSF of 24 of 81 patients with MS and were absent in the CSF of all headache controls. Median time to conversion to a secondary progressive course was 11 years in patients with bands and 22 years in patients without bands. Median time to an Expanded Disability Status Scale score of 4 was 14 years in patients with bands and 24 years in patients without bands. Conclusion The presence of lipid-specific immunoglobulin M bands in CSF predicts a more adverse long-term outcome in patients with MS; it may thus define a subset of patients who might benefit from aggressive treatment during the early phase of the disease.

GAD65 IgG autoantibodies in stiff person syndrome: clonality, avidity and persistence

Persistent intrathecal production of IgG autoantibodies against glutamic acid decarboxylase 65 (GAD65 IgG) and oligoclonal IgG of undetermined specificity has been reported in stiff person syndrome (SPS). To chart the avidity and clonal patterns of GAD65 IgG, we performed scatchard plot of binding characteristics and isoelectric focusing-immunoblot of cerebrospinal fluid (CSF) and serum from five SPS patients. Oligoclonal GAD65 IgG bands, predominantly restricted to the IgG1 subclass, were detected in CSF and serum in all patients. The distribution of GAD65-specific IgG bands in serum and CSF revealed intrathecal synthesis of oligoclonal GAD65 IgG in all five patients, whilst radioimmunoassay demonstrated intrathecal synthesis of GAD65 IgG in four. The binding avidity of GAD65 IgG from CSF was more than 10 times higher than in serum in two of the patients but did not differ substantially in the remaining three. These differences were not related to symptom severity. The pattern of oligoclonal GAD65 IgG bands in CSF and serum in three patients examined remained unchanged for up to 7 years after symptom debut. This study confirms the persistent systemic and intrathecal production of GAD65-specific IgG in SPS, and further shows that this immune response is oligoclonal and mediated by a stable population of affinity maturated B cell clones.

Detection of oligoclonal bands in cerebrospinal fluid from German Shepherd dogs with degenerative myelopathy by isoelectric focusing and immunofixation

Detection of intrathecal IgG synthesis is important in evaluating inflammatory diseases in the central nervous system. Isoelectric focusing (IEF) is currently the most sensitive method to demonstrate intrathecal IgG synthesis and may have diagnostic value for German Shepherd degenerative myelopathy (GSDM). The objective of this study was to adapt a modified IEF and immunofixation method for the detection of oligoclonal bands in cerebrospinal fluid (CSF) from dogs with GSDM. Serum and lumbar CSF samples were collected from 6 German Shepherd dogs clinically diagnosed with GSDM. Samples were also collected from 6 clinically healthy dogs for comparison. The concentration of IgG was measured by quantitative ELISA and the concentration of total protein was measured by the Bradford protein assay. The presence of oligoclonal bands was evaluated by use of modified IEF followed by immunofixation. The concentrations of total protein and IgG, and the IgG/total protein ratio in CSF samples, were not significantly different between GSDM patients and control dogs. Four GSDM patients had oligoclonal bands in their CSF based on IEF-immunofixation. No oligoclonal bands were found in CSF from control dogs. The results suggest that the detection of oligoclonal bands by IEF-immunofixation may have diagnostic value for GSDM, and support the idea that humoral immune responses may play a role in the pathogenesis of GSDM.

Antigen-specific oligoclonal bands in cerebrospinal fluid and serum from patients with anti-amphiphysin- and anti-CV2/CRMP5 associated paraneoplastic neurological syndromes

Using isoelectric focusing and affinity blotting employing paraneoplastic recombinant antigens, we investigated cerebrospinal fluid (CSF) and sera from three patients with positive anti-CV2/CRMP5- and one patient with positive anti-amphiphysin serology. CSF and sera were previously adjusted to total IgG concentrations of 20 mg/l. All patients suffered from paraneoplastic neurological syndromes (PNS) with predominant involvement of the central nervous system (CNS). Using affinity blot preloaded with paraneoplastic antigen, we detected in three of four patients more or stronger specific oligoclonal bands (OCB) in the CSF than in the corresponding serum, providing qualitative evidence of antigen specific intrathecal antibody synthesis. These results are in line with previous studies demonstrating specific OCB predominantly in CSF from patients with anti-Hu-, anti-Yo- and anti-Ri-associated PNS, supporting the hypothesis of autoimmunity in the pathogenesis of PNS. One patient harboured extensive anti-amphiphysin specific OCB, although OCB of total IgG could not be detected, indicating a higher sensitivity for detection of intrathecal antibody synthesis of the affinity blot preloaded with the paraneoplastic antigen, compared with investigation of total IgG OCB. These results could have implications concerning pathophysiological autoimmune aspects in other inflammatory diseases of CNS associated with total IgG OCB, provided that the target antigen is known.

Chronic Herpes Simplex Virus Encephalitis in Childhood

Although herpes simplex virus is a major cause of acute encephalitis in childhood, chronic herpes simplex virus encephalitis has only rarely been reported. This report presents a case of chronic herpes simplex virus encephalitis in a 6-year-old female. Diagnosis was based on the detection of herpes simplex virus deoxyribonucleic acid by polymerase chain reaction in combination with the cerebrospinal fluid/serum ratio of herpes simplex virus-specific immunoglobulin G, the presence of herpes simplex virus-specific oligoclonal immunoglobulin G bands in cerebrospinal fluid, and calcifications in the temporal regions found on cerebral computed tomographic scan. Prolonged antiviral therapy was beneficial to later mental development.

Multiphasic disseminated encephalomyelitis, uncommon cause for central demyelination in children

This case report is presented with the aim of discussing differential diagnosis of CNS demyelinating diseases in children below 15 years of age. The various diagnoses range from acute disseminated demyelinating disease to multiple sclerosis. In between the two extremes, we have multiphasic demyelinating encephalomyelitis. We had discussed the role of oligoclonal band in cerebrospinal fluid, auto antibodies and magnetic resonance imaging to differentiate these diagnoses.

Demonstration of components of antigen 85 complex in cerebrospinal fluid of tuberculous meningitis patients.

Tuberculous meningitis (TBM) is the most common form of chronic infection of the central nervous system. Despite the magnitude of the problem, the general diagnostic outlook is discouraging. Specifically, there is no generally accepted early confirmative diagnosis protocol available for TBM. Various Mycobacterium tuberculosis antigens are now recognized as potential markers for diagnosis of TBM. However, their presence remains questionable, and many of these antigens are reported in the blood but not in the cerebrospinal fluid (CSF). This study identifies a specific protein marker in CSF which will be useful in early diagnosis of TBM. We have demonstrated the presence of a 30-kDa protein band in CSF of 100% (n = 5) of confirmed and 90% (n = 138) of suspected TBM patients out of 153 TBM patients. The 30-kDa band was excised from the gel, destained extensively, and digested with trypsin. The resulting peptides were analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Partially purified proteins from CSF samples of TBM were analyzed by two-dimensional polyacrylamide gel electrophoresis and Western blotting. Immunoblotting and enzyme-linked immunosorbent assay (ELISA) were performed to confirm the presence of proteins in the 30-kDa protein band. The antigen 85 (Ag 85) complex was detected in CSF of TBM patients by indirect ELISA using antibodies against Ag 85 complex. The results of this study showed the 30-kDa protein band contained MTB proteins Rv3804c (Ag85A) and Rv1886c (Ag 85B), both members of the Ag85 complex. This was also confirmed by using immunotechniques such as indirect ELISA and the dot immunobinding assay. Detection of Ag85 complex was observed in CSF of 89% (71 out of 80) of suspected TBM patients that were 30-kDa protein positive. The observed 30-kDa protein in the CSF is comprised of the MTB Ag85 complex. This protein was earlier reported to be present in the blood of patients with extra-central nervous system tuberculosis. Therefore, this finding suggests that this protein can be used as a molecular marker for any type of tuberculous infection. It also provides a more sensitive immunoassay option for the early and confirmatory diagnosis of TBM.

Early Differential Diagnosis of Multiple Sclerosis Using a New Oligoclonal Band Test

Intrathecal IgG synthesis (ITGS), in conjunction with magnetic resonance imaging, can help in the early diagnosis of multiple sclerosis (MS). Recently, we developed a new oligoclonal IgG band (OCGB) test for ITGS detection that is more sensitive and easier to interpret than previously described methods. To assess the accuracy of a new OCGB detection test in the diagnosis of MS. Prospective observational study. A hospital neurology department. Patients A total of 385 patients with various neurologic disorders. The sensitivity and specificity of the OCGB detection test for MS diagnosis. Intrathecal IgG synthesis was found in 127 patients with MS (96.2%), 18 (35.3%) with central nervous system infections, and 1 with motor neuron disease. Two patterns reflected ITGS. One pattern, showing OCGBs restricted to cerebrospinal fluid, was predominantly found in MS. The other pattern, with OCGBs in serum and additional bands in cerebrospinal fluid, was mostly found in central nervous system infections. No patients with other inflammatory neurologic diseases showed ITGS. These patients frequently displayed a mirror pattern, with identical bands in serum and cerebrospinal fluid. Considering all patients, the sensitivity for the diagnosis of MS was 96.2%, and the specificity was 92.5%. Excluding infections, which usually do not present a differential diagnosis problem with MS, the sensitivity was still 96.2%, and the specificity increased to 99.5%. The accuracy of this OCGB method reinforces the value of cerebrospinal fluid studies in the early differential diagnosis of MS.

Cluster analysis method in electrophoretic patterns classification

The conventional electrophoresis methods are well known techniques for protein detection and analysis of cerebrospinal fluid (CSF). Disc electrophoresis (DEP) was carried out for detection of oligoclonal IgG bands in cerebrospinal fluid (CSF) on polyacrilamide gel. However, the advance of automation has made rapid collection of large amounts of data feasible and the development of microcomputers has made sophisticated processing even of old electrophoregrams possible. Automated analysis, data storage and sophisticate data acquisition were carried out with Gel Pro Analyzer 3.1, which is specifically structured to analyze gels and elctrophoregrams: complex band pattern matching (gel variation, dendogram analysis etc.); lane relation studies (sophisticated lane database); general gel analysis (accurate molecular size, quantitative determination of protein mixture etc.). Clustering techniques have been applied for detection of intrathecal immune response. Different hierarchic cluster analysis methods such as single linkage, complete linkage, unweighted pair-group average (UPMGA) were used. In addition, other cluster characteristics such, distance matrix and Euclidean distance matrix were calculated. Pairing of electrophoresis methods and cluster image analysis, could lead to additional diagnostic information of inflammatory conditions of the central nervous system (CNS) or dysfunction of blood-CSF barrier.

Recurrent Bilateral Inflammatory Idiopathic Optic Neuropathy Treated with Mycophenolate Mofetil: Clinical and Radiological Course

Objective: To report the clinical characteristics and radiological findings of a patient suffering simultaneous bilateral recurrent inflammatory optic neuritis, who has been free of relapses following treatment with mycophenolate mofetil (MMF). Background: Inflammatory simultaneous visual loss is unusual. It is more frequently seen in acute disseminated encephalomyelitis (ADEM) or neuromyelitis optica (NMO). Evolution to multiple sclerosis (MS) after simultaneous bilateral optic neuritis is less frequent than after unilateral optic neuritis. Sequential optic neuritis has been described in Chronic Relapsing Inflammatory Optic Neuritis (CRION), which shows neither brain lesions nor oligoclonal bands in cerebrospinal fluid (CSF) and presents a relapsing course and a good response to immunosuppression. Case: A 41-year-old woman was evaluated for simultaneous bilateral visual loss. Magnetic resonance imaging showed enhancement of the chiasm and both optic nerves. No definite data of MS were found. We excluded infections, sarcoidosis, lupus, and other known causes of optic neuropathy. She was treated with intravenous methylprednisolone and tapering oral prednisone. After a partial recovery, she suffered two recurrences within three months. Following treatment with MMF, no further relapses have occurred during a 26 month follow-up. Discussion: Bilateral optic neuritis is part of two clinical syndromes: ADEM and NMO. Our patient differs from these entities on her clinical course and response to treatment. She is closer to the CRION cases (no oligoclonal bands, relapsing course, response to immunosuppression), except for her brain lesions and the bilateral involvement at onset. Conclusion: We suggest MMF as an effective treatment for idiopathic recurrent inflammatory optic neuritis not responsive to corticosteroids.

An ultrasensitive method for the detection of oligoclonal IgG bands.

We have developed an ultrasensitive isoelectrofocusing (IEF) method for the detection of oligoclonal (OGC) IgG bands in cerebrospinal fluid (CSF) and sera. In this procedure, double antibody and peroxidase immunodetection have been substituted by a single antibody labelled with alkaline phosphatase. Alkaline phosphatase immunodetection not only improves tenfold the sensitivity of the assay but also gives a sharper pattern resolution making the interpretation easier and increases the specificity of this technique. This preliminary report should be validated in a larger number of patients with and without multiple sclerosis (MS).

Optimizing Detection of Oligoclonal Bands in Cerebrospinal Fluid by Use of Isoelectric Focusing With IgG Immunoblotting

Optimizing Detection of Oligoclonal Bands in Cerebrospinal Fluid by Use of Isoelectric Focusing With IgG Immunoblotting

Idiopathic recurrent transverse myelitis.

To determine whether idiopathic recurrent transverse myelitis (RTM) can be distinguished from multiple sclerosis-associated RTM (MSRTM) on the basis of clinical manifestations of myelopathy, or findings from magentic resonance imaging or cerebrospinal fluid examination. A retrospective analysis of 37 cases was conducted. Patients were classified as having idiopathic RTM on the basis of recurrent myelitis confirmed by clinical manifestations of myelopathy and magnetic resonance imaging findings. On review patients with idiopathic RTM had normal cranial magnetic resonance imagings and did not demonstrate paraclinical evidence of spatial dissemination beyond the spinal cord of the disease process. Patients were classified as having MSRTM on the basis of criteria of Poser et al for clinically definite multiple sclerosis involving the central nervous system. Fifteen patients met study criteria for idiopathic RTM. Twenty-two patients had MSRTM. Asan Medical Center, Seoul, South Korea, from January 1, 1992, through December 31, 2001. Presenting symptoms and clinical manifestations, relapsing times, magnetic resonance imaging features (involved spinal cord segments in T2-weighted images and gadolinium 64-enhanced lesions on T1-weighted images), IgG index, and oligoclonal bands in cerebrospinal fluid were compared. Idiopathic RTM occurred preponderantly in male patients and presented more often with acute transverse myelitis than did MSRTM. More than 2 relapses occurred in 6 cases (40%) of idiopathic RTM. The involved segments of spinal cord on T2-weighted images were not significantly different in idiopathic RTM and MSRTM, with enhancing lesions mostly in the posterior columns, and the spinothalamic and spinocerebellar tracts of white matter. Additionally, almost all patients with idiopathic RTM had normal cerebrospinal fluid indexes. Idiopathic RTM might be a disease entity distinct from MSRTM, differing in its male preponderance, absence of oligoclonal bands, frequent multiple relapses, and frequent presentation as acute transverse myelitis.

Qualitative evidence of anti-Yo-specific intrathecal antibody synthesis in patients with paraneoplastic cerebellar degeneration

We investigated the presence of anti-Yo-specific oligoclonal antibody bands in cerebrospinal fluid (CSF) and serum samples of 9 patients with anti-Yo syndrome and 11 controls. Isoelectric focusing combined with affinity blotting, revealed anti-Yo-specific intrathecal antibody synthesis in all patients with anti-Yo syndrome: Four patients had positive anti-Yo-specific oligoclonal IgG bands in CSF which were not demonstrable in their sera; five CSF/serum pairs showed additional, more intensive, oligoclonal bands in CSF compared to the corresponding serum. Interestingly, four patients with absence of oligoclonal bands of total IgG in CSF revealed positive anti-Yo-specific oligoclonal bands in the same sample. This speaks for a higher sensitivity of detection of oligoclonal bands using an affinity blot loaded with Yo-specific antigen compared to an affinity blot coated with anti-human IgG used for the detection of oligoclonal bands of total IgG. In conclusion, the presence of anti-Yo-specific oligoclonal IgG bands in CSF which were absent, or less strong, in patients sera provides qualitative evidence of anti-Yo-specific IgG synthesis by intrathecal B-cell clones. These results could be of interest in detection of intrathecal-specific IgG synthesis in nervous system infectious diseases provided that the target antigen is known.

Predicting multiple sclerosis at optic neuritis onset.

Using multivariate analyses, individual risk of clinically definite multiple sclerosis (CDMS) after monosymptomatic optic neuritis (MON) was quantified in a prospective study with clinical MON onset during 1990-95 in Stockholm, Sweden. During a mean follow-up time of 3.8 years, the presence of MS-like brain magnetic resonance imaging (MRI) lesions and oligoclonal immunoglobulin (Ig) G bands in cerebrospinal fluid (CSF) were strong prognostic markers of CDMS, with relative hazard ratios of 4.68 [95% confidence interval (CI) 2.21-9.91] and 5.39 (95% CI 1.56-18.61), respectively. Age and season of clinical onset were also significant predictors, with relative hazard ratios of 1.76 (95% CI 1.02-3.04) and 2.21 (95% CI 1.13-3.98), respectively. Based on the above two strong predictors, individual probability of CDMS development after MON was calculated in a three-quarter sample drawn from a cohort, with completion of follow-up at three years. The highest probability, 0.66 (95% CI 0.48-0.80), was obtained for individuals presenting with three or more brain MRI lesions and oligoclonal bands in the CSF, and the lowest, 0.09 (95% CI 0.02-0.32), for those not presenting with these traits. Medium values, 0.29 (95% CI 0.13-0.53) and 0.32 (95% CI 0.07-0.73), were obtained for individuals discordant for the presence of brain MRI lesions and oligoclonal bands in the CSF. These predictions were validated in an external one-quarter sample.

Molecular heterogeneity, detected by two electrophoretic micro procedures, of IgG in human cerebrospinal fluid (CSF).

Semi-automated electrophoretic procedures in the PhastSystem (Amersham Pharmacia Biotech) with micro polyacrylamide gels (PAGs) and SDS-PAG gradients were modified to analyze IgG in human cerebrospinal fluid (CSF) and matched serum samples with respect to the molecular IgG structure L-H-H-L. Isoelectric focusing (IEF) with specific immunofixation detected discrete IgG bands in CSF standing out against a polyclonal and monoclonal background pattern in CSF and serum; they were denoted oligoclonal bands (IgG OBs) (OB assay positive) indicating IgG synthesis in the central nervous system (CNS) of patients with subacute and chronic processes of inflammatory CNS disorders; assay was negative with identical (mirror) bands in CSF and serum for other CNS processes. IgG OBs were specified as lambda (kappa) IgG subfractions, precipitated with the anti-light (L) chains lambda (kappa) and anti-heavy (H) chain fragments (Fd, Fc, C(H)2) as well as with anti-F(ab')(2), and as duplex IgGs with kappa and lambda OBs at the same pI. With SDS-PAG gradient electrophoresis and specific immunofixation more than six IgG fractions were detected and classed according to apparent molecular weights of a S-sulfonated human IgG standard; they were characterized with the monospecific antibodies against the L and H chain fragments as 25, 50, 75, 100, 125 and 150 kD fractions containing combinations of L and H chains as well as mixtures of both L and H chain fragments of varying dimensions. Generally, this molecular IgG heterogeneity could not be connected with the IgG OB heterogeneity revealed by IEF; but single OBs in the strongly alkaline pH region of PAG may correspond to H fragments with basic pI. Nevertheless, evidence for the existence of both free L chains and the free H chain were revealed as specific OBs with IEF and with the anti-L and anti-H antibodies in the 25 kD and 50 kD fractions, respectively, of CSF samples of six patients with diverse CNS diseases. Further experiments are needed to elicit the origin of the molecular IgG heterogeneity during the immune response of subacute and chronic inflammatory processes in human CNS.

Intrathecal IgM synthesis is a prognostic factor in multiple sclerosis.

Intrathecal IgM synthesis (ITMS) predicts a worse evolution in the first stages of multiple sclerosis (MS). The aim of this study was the follow-up of a group of relapsing-remitting MS patients for a longer time to evaluate whether the ITMS implies a poor prognosis. Oligoclonal IgM bands were performed in 29 MS patients followed up from 5 to 16 years. Time to conversion to secondary-progressive MS (SPMS), time elapsed to reach a disability of 6 in the Expanded Disability Status Scale (EDSS), percentage of patients with a benign MS, and changes in EDSS score were evaluated. During the follow-up, 70.8% of patients with ITMS converted to SPMS. None of the patients without ITMS did. At the end of the study, 63.6% of patients with ITMS had reached EDSS 6, whereas none of the patients lacking ITMS reached values above EDSS 3. When patients with benign MS were analyzed, 82% lacked ITMS. All patients with a nonbenign MS had ITMS. At the end of the study, the mean EDSS score was 4.64 in patients with ITMS and 1.31 in those without. The presence of oligoclonal IgM bands in cerebrospinal fluid is an unfavorable prognostic marker in MS.

Comparison of Methods for the Detection of Oligoclonal IgG Bands in Cerebrospinal Fluid and Serum: Results of the Dutch Quality Control Survey

Detection of oligoclonal IgG bands (OCBs) in parallel cerebrospinal fluid (CSF) and serum samples is an important tool to support the diagnosis of neuroinflammatory diseases such as multiple sclerosis (MS) (1). Because ∼90–95% of the patients diagnosed with MS present with OCBs in the CSF (2), whereas other CSF indices may be normal, this type of analysis has long been recommended for the diagnosis of MS, especially when the clinical presentation does not clearly suggest this diagnosis (1)(3). CSF-restricted OCBs are also essential for the diagnosis of primary progressive MS (1). Furthermore, in several neuroimmunologic disorders, including neuroborreliosis, neurosyphilis, and viral infections of the brain, the identification of OCBs in CSF may be helpful in the diagnostic process (2)(4)(5). Twice a year, pairs of CSF and serum samples are distributed by our laboratories to the participants of the Dutch CSF Quality Control survey for analysis of OCBs. It was the aim of this study to evaluate the performance of the 56 participating laboratories for OCB analysis with regard to both the methods used for protein separation and detection of OCBs and to derive a general recommendation on laboratory management for this type of analysis. To collect a sufficient volume of CSF, samples stored at −80 °C and selected for the absence of OCBs were pooled. Sera taken from healthy controls were collected and pooled as well. Sera containing either a known OCB pattern or monoclonal IgG were also collected with informed consent from patients. We added minimal amounts of these clinical serum samples to the CSF pool to create artificial patient CSF samples. In each survey, an OCB-enriched CSF sample and a serum sample were sent out as a pair of clinical CSF and serum samples. In this way we were able to …

Expansion of CD5 - B cells in multiple sclerosis correlates with CD80 (B7-1) expression.

The pathogenetic role of autoantibodies in multiple sclerosis (MS) is uncertain. CD5+ B cells commonly produce autoantibodies, but CD5 expression has also been implicated in B-cell tolerance. We studied B-cell subsets, anti-myelin protein antibody-secreting cells in cerebrospinal fluid (CSF) and a panel of serum autoantibodies in patients with clinically isolated syndromes (CIS), suggestive of MS and patients with clinically definite MS (CDMS). Patients with CDMS had a higher percentage of CD5- B cells in CSF than did control subjects (P = 0.02). CIS patients with immunoglobulin G (IgG) oligoclonal bands in CSF or multiple lesions on magnetic resonance imaging (MRI) had a higher percentage of CD5- B cells in CSF than did the remaining CIS patients (P = 0.03). The percentage of CD5- and CD80+ B cells correlated positively and the percentage of CD5+ B cells correlated negatively with the number of CSF cells secreting anti-myelin basic protein (anti-MBP) antibodies. The prevalence of serum autoantibodies was comparable in the three patient groups. We conclude that intrathecal expansion of CD5- B cells appears to be more characteristic in MS patients, and CD5+ B cells may be associated with a lower prevalence of anti-myelin antibody production.