Original Article
Antimyelin Antibodies as a Predictor of Clinically Definite Multiple Sclerosis after a First Demyelinating Event
N Engl J Med 2003; 349:139-145July 10, 2003
- Abstract
Background
Most patients with multiple sclerosis initially present with a clinically isolated syndrome. Despite the fact that clinically definite multiple sclerosis will develop in up to 80 percent of these patients, the course of the disease is unpredictable at its onset and requires long-term observation or repeated magnetic resonance imaging (MRI). We investigated whether the presence of serum antibodies against myelin oligodendrocyte glycoprotein (MOG) and myelin basic protein (MBP) in patients with a clinically isolated syndrome predicts the interval to conversion to clinically definite multiple sclerosis.
Methods
A total of 103 patients with a clinically isolated syndrome, positive findings on cerebral MRI, and oligoclonal bands in the cerebrospinal fluid were studied. At base line, serum samples were collected to test for anti-MOG and anti-MBP antibodies with Western blot analysis, and the lesions detected by cerebral MRI were quantified. Neurologic examinations for relapse or disease progression (defined as conversion to clinically definite multiple sclerosis) were performed at base line and subsequently every three months.
Results
Patients with anti-MOG and anti-MBP antibodies had relapses more often and earlier than patients without these antibodies. Only 9 of 39 antibody-seronegative patients (23 percent) had a relapse, and the mean (±SD) time to relapse was 45.1±13.7 months. In contrast, 21 of 22 patients (95 percent) with antibodies against both MOG and MBP had a relapse within a mean of 7.5±4.4 months, and 35 of 42 patients (83 percent) with only anti-MOG antibodies had a relapse within 14.6±9.6 months (P<0.001 for both comparisons with antibody-seronegative patients). The adjusted hazard ratio for the development of clinically definite multiple sclerosis was 76.5 (95 percent confidence interval, 20.6 to 284.6) among the patients who were seropositive for both antibodies and 31.6 (95 percent confidence interval, 9.5 to 104.5) among the patients who were seropositive only for anti-MOG antibodies, as compared with the seronegative patients.
Conclusions
Analysis of antibodies against MOG and MBP in patients with a clinically isolated syndrome is a rapid, inexpensive, and precise method for the prediction of early conversion to clinically definite multiple sclerosis. This finding may be important for the counseling and care of patients with a first demyelinating event suggestive of multiple sclerosis.
Media in This Article
Figure 1
Kaplan–Meier Estimates of the Risk of Clinically Definite Multiple Sclerosis, According to Antibody Status.Table 1
Characteristics of the 103 Patients and Their Disease, According to Antibody Status.Article Activity
- Article
Multiple sclerosis is the most common disabling neurologic disease in young adults.1 Ninety percent of patients with multiple sclerosis initially present with a clinically isolated syndrome due to an inflammatory demyelinating lesion in the optic nerve, brain stem, or spinal cord.2 Thirty percent of these patients with a clinically isolated syndrome will have progression to clinically definite multiple sclerosis within 12 months after presentation.2-4 The course of disease in multiple sclerosis is highly variable and hard to predict, ranging from a benign course to a classic relapsing–remitting, chronic progressive, or rare fulminant course, despite several clinical,5-8 immunologic,9 and radiologic2,4,10 investigations to identify risk factors for disease progression. In patients presenting with a first demyelinating event, the individual prognosis and prediction of clinically definite multiple sclerosis would be of value for counseling and management.11 Patients at high risk for rapid progression to clinically definite multiple sclerosis could be offered disease-modifying treatments, which have recently been shown to be beneficial in early multiple sclerosis.12,13
The pathogenetic mechanisms responsible for conversion from a clinically isolated syndrome to clinically definite multiple sclerosis are still unknown but may include ongoing axonal loss,14 with subsequent cumulative disability, and the process of epitope spreading,15,16 which may amplify inflammatory demyelination in the central nervous system. After the initial inflammatory demyelinating event, further epitope spreading may prime autoreactive cellular and humoral immune responses to target additional myelin and nonmyelin antigens or epitopes.15-18 Thus, amplification of the autoimmune process could account for disease progression in multiple sclerosis.19 Another possible mechanism is antibody-mediated demyelination.20-22 It is known that antibodies against myelin basic protein (MBP) are present in early multiple sclerosis.23,24 Another potential target antigen for autoreactive antibodies might be myelin oligodendrocyte glycoprotein (MOG), which is specific to the central nervous system and is located exclusively on the surface of myelin sheaths and oligodendrocytes.25 Antibodies against MOG cause demyelination in vitro26 and in animal models of multiple sclerosis27,28 and have been found in active lesions in patients with multiple sclerosis.29 A substantial subgroup of patients with multiple sclerosis mount a persistent autoantibody response to the extracellular immunoglobulin domain of MOG30 with a predominance of anti-MOG IgM antibodies.23,24
In this study, we examined whether the presence of serum anti-MOG and anti-MBP antibodies predicts conversion to clinically definite multiple sclerosis among patients who have a clinically isolated syndrome and findings on magnetic resonance imaging (MRI) and cerebrospinal fluid analysis that are suggestive of multiple sclerosis.
Methods
Patients
Patients with a first acute neurologic event suggestive of multiple sclerosis were enrolled in the study after their written informed consent to the protocol, as approved by the institutional review board, had been obtained. All the patients underwent cerebral MRI (T2-weighted and gadolinium-enhanced, T1-weighted scanning) within two weeks after the onset of the initial neurologic symptom. Patients were excluded from the study if they did not have typical disseminated white-matter lesions according to Fazekas and colleagues' criteria.31 In addition, initial diagnostic examination of the cerebrospinal fluid was performed in all the patients, and those whose cerebrospinal fluid did not show oligoclonal bands were excluded. Patients were also excluded from the study if they had a history of any kind of previous neurologic symptoms or signs; clinical, laboratory, MRI, or cerebrospinal fluid findings suggestive of any diagnosis other than multiple sclerosis32; or primary progressive multiple sclerosis (diagnosed before month 12).
All the patients were treated initially with 1000 mg of intravenous methylprednisolone for three to five consecutive days. The follow-up period of clinical monitoring for further relapses or disease progression lasted at least 12 months. Each patient underwent neurologic examination at base line and subsequently on a scheduled basis every three months by neurologists who were unaware of the antibody status of the patient. Neurologic examinations included repeated interviews and assessments for symptoms suggestive of relapse or disease progression. If a relapse was suspected, it had to be confirmed by one of the neurologists as consisting of the onset of a new neurologic symptom or the exacerbation of a previous symptom for at least 48 hours and at least four weeks after the initial demyelinating event. Exacerbations due to exogenous triggers (e.g., drugs, heat, fever, or infection) were judged not to be relapses. If a relapse was confirmed, the patient was given the diagnosis of clinically definite multiple sclerosis.
Antibody Analysis
Serum samples for antibody analysis were collected at base line, before methylprednisolone treatment. The people performing the antibody analyses were unaware of the patient's clinical status and MRI findings. Human recombinant MOG immunoglobulin and human myelin–derived MBP were prepared as previously described.23 Anti-MOG and anti-MBP antibodies were analyzed by Western blotting, also as previously described23,24 but with minor modifications, as follows. In brief, either 1 μg of recombinant MOG immunoglobulin or 2 μg of MBP was loaded in each lane and separated in 10 percent Bis-Tris (NuPAGE) sodium dodecyl sulfate (SDS)–polyacrylamide gels (Novex). Separated proteins were electrotransferred to nitrocellulose membranes (Hybond-C, Amersham). The efficiency of transfer was monitored by the use of a prestained, low-range SDS–polyacrylamide gel electrophoresis standard (Bio-Rad) and by staining of the filters with Ponceau S (Sigma) after transfer.
The blots were blocked with 2 percent milk powder in phosphate-buffered saline containing 0.05 percent Tween 20. The blots were then dried, cut into 2-mm nitrocellulose strips with a membrane cutter (Novex), and probed overnight at 4°C with diluted human serum (dilution, 1:500 in 2 percent milk powder in phosphate-buffered saline containing 0.05 percent Tween 20). The strips were then washed three times with phosphate-buffered saline containing 0.05 percent Tween 20 and incubated with alkaline phosphatase–conjugated antihuman IgM (dilution, 1:5000; JGH055043, Jackson) for one hour at room temperature.
After washing, bound antibodies were detected by nitroblue tetrazolium chloride and 5-bromo-4-chloro-3-indolyl-phosphate (both, Roche Molecular Diagnostics). The strips were then washed with distilled water and dried, and the immunoreactivity of the serum samples was assessed by two independent investigators. A serum sample was considered to be positive if the immunoreactivity was equal to or greater than that of a control sample. As controls, monoclonal antibodies to MBP (MAB381, Chemicon) and MOG (8.18-C5)25 and positive and negative human serum samples were used. Monoclonal anti-MOG antibody 8.18-C5 and positive human serum samples are available on request to interested parties who wish to replicate our results.
Statistical Analysis
The characteristics of the patients and their disease were compared among the groups according to antibody status with the use of one-way analysis of variance, chi-square testing, or Kruskal–Wallis testing. The cumulative risk of the development of clinically definite multiple sclerosis was calculated for each group according to the Kaplan–Meier method, and differences between the groups were evaluated in a univariate analysis with the log-rank test. The Cox proportional-hazards model was used to assess the predictive value of anti-MOG and anti-MBP antibodies in a multivariable analysis, with adjustment for potential confounding variables. The final model included age, sex, the duration of disease, the IgG index (calculated according to the formula [cerebrospinal fluid IgG ÷ serum IgG] ÷ [cerebrospinal fluid albumin ÷ serum albumin], with a usual upper limit of 0.65),33 and the number of lesions on MRI. The relative risk of the development of clinically definite multiple sclerosis is expressed as a hazard ratio and 95 percent confidence interval. After Bonferroni's correction for three comparisons, P values of less than 0.017 were considered to indicate statistical significance.
Results
A total of 119 patients were consecutively identified as potential study participants between March 1994 and March 2001. Nine of these patients were initially excluded because oligoclonal bands were not detected in their cerebrospinal fluid. Seven additional patients were excluded because of primary progressive multiple sclerosis. None of the remaining 103 patients received any disease-modifying treatment between the time of enrollment in the study and the diagnosis of clinically definite multiple sclerosis, if such a diagnosis was made. Ninety-six patients (93 percent) were clinically monitored on a scheduled basis every three months; for only seven patients was there one six-month interval between scheduled clinical visits. None of the 103 patients were lost to follow-up during the study period.
Seventy-three of the 103 patients were female and 30 were male; their mean age at the onset of disease was 32.0 years (range, 13 to 54), and as of February 28, 2002, the mean follow-up period was 50.9 months (range, 12 to 96). The characteristics of the patients and their disease are shown in Table 1Table 1
Characteristics of the 103 Patients and Their Disease, According to Antibody Status.. The types of symptoms seen at presentation were distributed similarly among the groups of patients. Antibody status was not associated with the type of clinical syndrome or the clinical outcome. Twenty-two patients (21 percent) were seropositive for both anti-MOG and anti-MBP antibodies, 42 patients (41 percent) were seropositive only for anti-MOG antibodies, and 39 patients (38 percent) were seronegative for both anti-MOG and anti-MBP antibodies.Table 2Table 2
Number of Relapses and Length of Relapse-free Period, According to Antibody Status. shows the number of patients with a relapse and the mean relapse-free period according to the antibody status. Only 9 of the 39 patients who were seronegative for anti-MOG and anti-MBP antibodies (23 percent) had had a relapse of multiple sclerosis as of February 28, 2002. Eight of these patients were seropositive for anti-MOG antibodies at the time of their relapse. In contrast, 35 of the 42 patients (83 percent) with antibodies against MOG (but not against MBP) and 21 of the 22 patients (95 percent) with antibodies against both MOG and MBP had a relapse during the study period (P<0.001 for both comparisons with the patients who had neither antibody).Of the patients who had a relapse during the study period, those who were seronegative for anti-MOG and anti-MBP antibodies had their first relapse after a mean (±SD) interval of 45.1±13.7 months. In contrast, patients who initially were seropositive for both anti-MOG and anti-MBP antibodies had their first relapse after only 7.5±4.4 months (P<0.001 for the comparison with the seronegative patients). For patients with anti-MOG antibodies but not anti-MBP antibodies, the mean time to relapse was 14.6±9.6 months (P<0.001 for the comparison with the seronegative patients). Of the nine patients excluded from the study because of the absence of oligoclonal bands in the cerebrospinal fluid, only one was seropositive for anti-MOG antibodies. This patient had his first relapse after 16 months.
Figure 1Figure 1
Kaplan–Meier Estimates of the Risk of Clinically Definite Multiple Sclerosis, According to Antibody Status. shows that the risk of clinically definite multiple sclerosis was significantly lower among the patients who were seronegative for both anti-MOG and anti-MBP antibodies than among those who were seropositive only for anti-MOG antibodies or for both anti-MOG and anti-MBP antibodies (P<0.001 for both comparisons, by the log-rank test). The multivariate analysis (Table 3Table 3
Hazard Ratios for the Development of Clinically Definite Multiple Sclerosis.) revealed that seropositivity for anti-MOG but not anti-MBP antibodies was associated with a risk of clinically definite multiple sclerosis that was 32 times the risk associated with seronegativity for both antibodies (adjusted hazard ratio, 31.6; 95 percent confidence interval, 9.5 to 104.5; P<0.001). Seropositivity for both anti-MOG and anti-MBP antibodies was associated with a risk that was 76 times the risk associated with seronegativity (adjusted hazard ratio, 76.5; 95 percent confidence interval, 20.6 to 284.6; P<0.001).One of us, who had no access to the patients' clinical information or information about their antibody status, assessed and counted the number of lesions seen on T2-weighted and T1-weighted, gadolinium-enhanced MRI. As expected, patients with both anti-MOG and anti-MBP antibodies had higher mean numbers of lesions on T2-weighted and T1-weighted, gadolinium-enhanced MRI than did patients who were seronegative for the antibodies (Table 1). However, the number of lesions varied widely among the individual patients, from 2 to 17 lesions on T2-weighted MRI and from 0 to 4 lesions on T1-weighted, gadolinium-enhanced MRI. In adjusted analyses, the number of lesions seen on MRI was not independently associated with the risk of relapse (Table 3).
Discussion
Patients with a clinically isolated syndrome in whom neurologic symptoms, MRI examinations, and analyses of cerebrospinal fluid suggest that a given neurologic event is a first demyelinating event due to multiple sclerosis face an uncertain future. Previous studies have focused on such patients either to unravel the pathogenesis and dynamics of the progression of disease or to evaluate the benefit of early treatment.2,5-9,12,13 The importance of MRI in early multiple sclerosis has been demonstrated.2-4,10 Studies have shown that the number of lesions on T2-weighted MRI is associated with more than an 80 percent risk of conversion to multiple sclerosis within 10 years, that the number of lesions on initial contrast-enhanced MRI is associated with the development of multiple sclerosis within 3 years, and that increases in the volume of lesions seen on MRI correlate with the degree of long-term disability due to multiple sclerosis.2,4,10 Consequently, these MRI findings in early multiple sclerosis have added important information to new diagnostic guidelines in multiple sclerosis.34
In general, however, no clinical, radiologic, or immunologic variable allows precise prediction of the interval between presentation with a clinically isolated syndrome suggestive of multiple sclerosis and the presence of clinically definite multiple sclerosis. The uncertainty of prediction and prognosis causes uncertainty in individual counseling and management.
In this study, we were able to show that in individual patients with a clinically isolated syndrome, the initial detection of serum antibodies against MOG and MBP predicts early conversion to clinically definite multiple sclerosis, whereas the absence of these antibodies suggests that the patient will remain disease-free for several years. We found that 83 percent of the patients who were seropositive only for anti-MOG antibodies and 95 percent of those who were seropositive for both anti-MOG and anti-MBP had a first relapse during the mean follow-up period of 52 months, whereas 77 percent of the patients who were seronegative for both anti-MOG and anti-MBP antibodies remained relapse-free during that period.
Our results are consistent with data from previous long-term follow-up studies in some interesting ways. First, 30 to 40 percent of patients with multiple sclerosis are classified as having a relatively benign course of disease.5 In our study, 38 percent of the participants were seronegative for anti-MOG and anti-MBP antibodies. Antibody status may therefore identify, at the onset of disease, the patients who are likely to have a relatively benign course of disease. Second, in a recent trial of early treatment, patients in the placebo group had conversion to clinically definite multiple sclerosis within a mean period of 8.4 months.13 In the current study, patients who were seropositive for both anti-MOG and anti-MBP antibodies had clinically definite multiple sclerosis within a mean of 7.5 months.
Although, in general, antibodies against myelin are neither a specific nor a diagnostic feature of multiple sclerosis, it seems that specific demyelinating antibodies are involved in the immunopathogenesis of the disorder in at least a subgroup of patients.35,36 We would like to emphasize that we cannot prove whether the measured antimyelin antibodies in our patients are antibodies with demyelinating capacity or whether they represent an epiphenomenon of myelin destruction. However, seropositivity for anti-MOG and anti-MBP antibodies reflects the presence of active disease, which is corroborated by higher mean numbers of lesions on T2-weighted and T1-weighted, gadolinium-enhanced MRI in this group of patients, with subsequent early conversion to clinically definite multiple sclerosis. Thus, our data support the concept that antigen or epitope spreading in an early phase of disease correlates with the progression of disease.16,19
In our adjusted analyses, seropositivity for anti-MOG or both anti-MOG and anti-MBP antibodies, but not the number of lesions seen on MRI, was associated with an increased risk of relapse of multiple sclerosis. Thus, our study demonstrates that analysis of these antibodies, which is simple to perform and less expensive than MRI, can be used to estimate the individual risk of an early first relapse and therefore of clinically definite multiple sclerosis. The predictive value of antimyelin antibodies may be important for counseling purposes or for early treatment to prevent the disease from progressing.12,13 However, for antibody-seronegative patients, who have a chance of remaining relapse-free for several years after the initial demyelinating event, immunomodulatory therapy might be postponed until necessary.
Supported by a grant from the Austrian Federal Ministry of Science (GZ 70.059/2-Pr/4/99, to Drs. Berger and Reindl).
Dr. Berger reports having served as a paid consultant for Biogen and Medacorp and as a paid speaker for Biogen, Serono, Schering, Pfizer, and Aventis and having received grant support from Aventis and Biogen. Dr. Deisenhammer reports having served as a paid consultant for Biogen, Medacorp, and Schering and as a paid speaker for Biogen, Schering, and Serono and having received grant support from Biogen, Schering, and Serono.
We are indebted to Kathrin Schanda for excellent technical assistance.
Source Information
From the Department of Neurology (T.B., P.R., R.E., I.M., E.D., F.D., M.R.) and the Institute of Biostatistics (H.U.), University of Innsbruck, Innsbruck, Austria; and the Department of Neurology, County Hospital, Villach, Austria (F.S.).
Address reprint requests to Dr. Berger at the Department of Neurology, University of Innsbruck, Anichstrasse 35, A-6020 Innsbruck, Austria, or at thomas.berger@uibk.ac.at.
- References
References
1
Noseworthy JH ,Lucchinetti C ,Rodriguez M ,Weinshenker BG . Multiple sclerosis. N Engl J Med 2000;343:938-952
Full Text | Web of Science | Medline2
O'Riordan JI ,Thompson AJ ,Kingsley DPE , et al. The prognostic value of brain MRI in clinically isolated syndromes of the CNS: a 10-year follow-up. Brain 1998;121:495-503
CrossRef | Web of Science | Medline3
Jacobs LD ,Kaba SE ,Miller CM ,Priore RL ,Brownscheidle CM . Correlations of clinical, magnetic resonance imaging, and cerebrospinal fluid findings in optic neuritis. Ann Neurol 1997;41:392-398
CrossRef | Web of Science | Medline4
Brex PA ,Ciccarelli O ,O'Riordan JI ,Sailer M ,Thompson AJ ,Miller DH . A longitudinal study of abnormalities on MRI and disability from multiple sclerosis. N Engl J Med 2002;346:158-164
Full Text | Web of Science | Medline5
McAlpine D . The benign form of multiple sclerosis: a study based on 241 cases seen within three years of onset and followed up until the tenth year or more of the disease. Brain 1961;84:186-203
CrossRef | Web of Science | Medline6
Weinshenker BG ,Bass B ,Rice GP , et al. The natural history of multiple sclerosis: a geographically based study. 2. Predictive value of the early clinical course. Brain 1989;112:1419-1428
CrossRef | Web of Science | Medline7
Runmarker B ,Andersen O . Prognostic factors in a multiple sclerosis incidence cohort with twenty-five years of follow-up. Brain 1993;116:117-134
CrossRef | Web of Science | Medline8
Achiron A ,Barak Y . Multiple sclerosis -- from probable to definite diagnosis: a 7-year prospective study. Arch Neurol 2000;57:974-979
CrossRef | Web of Science | Medline9
Galboiz Y ,Miller A . Immunological indicators of disease activity and prognosis in multiple sclerosis. Curr Opin Neurol 2002;15:233-237
CrossRef | Web of Science | Medline10
Dalton CM ,Brex PA ,Miszkiel KA , et al. Application of the new McDonald criteria to patients with clinically isolated syndromes suggestive of multiple sclerosis. Ann Neurol 2002;52:47-53
CrossRef | Web of Science | Medline11
Rudick RA ,Cohen JA ,Weinstock-Guttmann B ,Kinkel RP ,Ransohoff RM . Management of multiple sclerosis. N Engl J Med 1997;337:1604-1611
Full Text | Web of Science | Medline12
Jacobs LD ,Beck RW ,Simon JH , et al. Intramuscular interferon beta-1a therapy initiated during a first demyelinating event in multiple sclerosis. N Engl J Med 2000;343:898-904
Full Text | Web of Science | Medline13
Comi G ,Filippi M ,Barkhof F , et al. Effect of early interferon treatment on conversion to definite multiple sclerosis: a randomised study. Lancet 2001;357:1576-1582
CrossRef | Web of Science | Medline14
Trapp BD ,Peterson J ,Ransohoff RM ,Rudick R ,Mork S ,Bo L . Axonal transection in the lesions of multiple sclerosis. N Engl J Med 1998;338:278-285
Full Text | Web of Science | Medline15
Lehmann PV ,Forsthuber T ,Miller A ,Sercarz EE . Spreading of T-cell autoimmunity to cryptic determinants of autoantigen. Nature 1992;358:155-157
CrossRef | Web of Science | Medline16
Vanderlugt CL ,Miller SD . Epitope spreading in immune-mediated diseases: implications for immunotherapy. Nat Rev Immunol 2002;2:85-95
CrossRef | Web of Science | Medline17
McFarland HI ,Lobito AA ,Johnson MM , et al. Determinant spreading associated with demyelination in a nonhuman primate model of multiple sclerosis. J Immunol 1999;162:2384-2390
Web of Science | Medline18
Goebels N ,Hofstetter H ,Schmidt S ,Brunner C ,Wekerle H ,Hohlfeld R . Repertoire dynamics of autoreactive T cells in multiple sclerosis patients and healthy subjects: epitope spreading versus clonal persistence. Brain 2000;123:508-518
CrossRef | Web of Science | Medline19
Yu M ,Johnson JM ,Tuohy VK . A predictable sequential determinant spreading cascade invariably accompanies progression of experimental autoimmune encephalomyelitis: a basis for peptide-specific therapy after onset of clinical disease. J Exp Med 1996;183:1777-1788
CrossRef | Web of Science | Medline20
Ozawa K ,Suchanek G ,Breitschopf H , et al. Patterns of oligodendroglia pathology in multiple sclerosis. Brain 1994;117:1311-1322
CrossRef | Web of Science | Medline21
Luccinetti CF ,Bruck W ,Rodriguez M ,Lassmann H . Distinct patterns of multiple sclerosis pathology indicate heterogeneity on pathogenesis. Brain Pathol 1996;6:259-274
CrossRef | Web of Science | Medline22
Storch MK ,Piddlesden S ,Haltia M ,Iivanainen M ,Morgan P ,Lassmann H . Multiple sclerosis: in situ evidence for antibody- and complement-mediated demyelination. Ann Neurol 1998;43:465-471
CrossRef | Web of Science | Medline23
Reindl M ,Linington C ,Brehm U , et al. Antibodies against the myelin oligodendrocyte glycoprotein and the myelin basic protein in multiple sclerosis and other neurological diseases: a comparative study. Brain 1999;122:2047-2056
CrossRef | Web of Science | Medline24
Egg R ,Reindl M ,Deisenhammer F ,Linington C ,Berger T . Anti-MOG and anti-MBP antibody subclasses in multiple sclerosis. Mult Scler 2001;7:285-289
Web of Science | Medline25
Brunner C ,Lassmann H ,Waehneldt TV ,Matthieu JM ,Linington C . Differential ultrastructural localization of myelin basic protein, myelin oligodendroglial glycoprotein, and 2',3'-cyclic nucleotide 3'-phosphodiesterase in the CNS of adult rats. J Neurochem 1989;52:296-304
CrossRef | Web of Science | Medline26
Kerlero de Rosbo N ,Honegger P ,Lassmann H ,Matthieu JM . Demyelination induced in aggregating brain cell cultures by a monoclonal antibody against myelin/oligodendrocyte glycoprotein. J Neurochem 1990;55:583-587
CrossRef | Web of Science | Medline27
Linington C ,Bradl M ,Lassmann H ,Brunner C ,Vass K . Augmentation of demyelination in rat acute allergic encephalomyelitis by circulating mouse monoclonal antibodies directed against a myelin/oligodendrocyte glycoprotein. Am J Pathol 1988;130:443-454
Web of Science | Medline28
Stefferl A ,Brehm U ,Storch M , et al. Myelin oligodendrocyte glycoprotein induces experimental autoimmune encephalomyelitis in the “resistant“ Brown Norway rat: disease susceptibility is determined by MHC and MHC-linked effects on the B cell response. J Immunol 1999;163:40-49
Web of Science | Medline29
Genain CP ,Cannella B ,Hauser SL ,Raine CS . Identification of autoantibodies associated with myelin damage in multiple sclerosis. Nat Med 1999;5:170-175
CrossRef | Web of Science | Medline30
Adelmann M ,Wood J ,Benzel I , et al. The N-terminal domain of the myelin oligodendrocyte glycoprotein (MOG) induces acute demyelinating experimental autoimmune encephalomyelitis in the Lewis rat. J Neuroimmunol 1995;63:17-27
CrossRef | Web of Science | Medline31
Fazekas F ,Offenbacher H ,Fuchs S , et al. Criteria for an increased specificity of MRI interpretation in elderly subjects with suspected multiple sclerosis. Neurology 1988;38:1822-1825
Web of Science | Medline32
Matthews B. Differential diagnosis of multiple sclerosis and related disorders. In: Compston A, Ebers G, Lassmann H, McDonald I, Matthews B, Wekerle H, eds. McAlpine's multiple sclerosis. 3rd ed. London: Churchill Livingstone, 1998:223-50.
33
Link H ,Tibblieng G . Principles of albumin and IgG analysis in neurological disorders. III. Evaluation of IgG synthesis within the central nervous system in multiple sclerosis. Scand J Clin Lab Invest 1977;37:397-401
CrossRef | Web of Science | Medline34
McDonald WI ,Compston A ,Edan G , et al. Recommended diagnostic criteria for multiple sclerosis: guidelines from the International Panel on the diagnosis of multiple sclerosis. Ann Neurol 2001;50:121-127
CrossRef | Web of Science | Medline35
Bruck W ,Neubert K ,Berger T ,Weber JR . Clinical, radiological, immunological and pathological findings in inflammatory CNS demyelination -- possible markers for an antibody-mediated process. Mult Scler 2001;7:173-177
Web of Science | Medline36
von Budingen HC ,Hauser SL ,Fuhrmann A ,Nabavi CB ,Lee JI ,Genain CP . Molecular characterization of antibody specificities against myelin/oligodendrocyte glycoprotein in autoimmune demyelination. Proc Natl Acad Sci U S A 2002;99:8207-8212
CrossRef | Web of Science | Medline
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CrossRef2
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Kemal Ugur Tufekci, Meryem Gulfem Oner, Sermin Genc, Kursad Genc. (2011) MicroRNAs and Multiple Sclerosis. Autoimmune Diseases 2011, 1-27
CrossRef18
Zhirong Qi, Hiroyuki Takamatsu, J. Luis Espinoza, Xuzhang Lu, Naomi Sugimori, Hirohito Yamazaki, Katsuya Okawa, Shinji Nakao. (2010) Autoantibodies specific to hnRNP K: a new diagnostic marker for immune pathophysiology in aplastic anemia. Annals of Hematology 89:12, 1255-1263
CrossRef19
Joanne L. Jones, Alasdair J. Coles. (2010) New treatment strategies in multiple sclerosis. Experimental Neurology 225:1, 34-39
CrossRef20
Edgar Meinl, Tobias Derfuss, Chris Linington. (2010) Identifying targets for autoantibodies in CNS inflammation: Strategies and achievements. Clinical and Experimental Neuroimmunology 1:2, 47-60
CrossRef21
M. Comabella, M. Fernandez, R. Martin, S. Rivera-Vallve, E. Borras, C. Chiva, E. Julia, A. Rovira, E. Canto, J. C. Alvarez-Cermeno, L. M. Villar, M. Tintore, X. Montalban. (2010) Cerebrospinal fluid chitinase 3-like 1 levels are associated with conversion to multiple sclerosis. Brain 133:4, 1082-1093
CrossRef22
Thomas Liggett, Anatoliy Melnikov, Shilpa Tilwalli, Qilong Yi, Haiyan Chen, Charles Replogle, Xuan Feng, Anthony Reder, Dusan Stefoski, Roumen Balabanov, Victor Levenson. (2010) Methylation patterns of cell-free plasma DNA in relapsing–remitting multiple sclerosis. Journal of the Neurological Sciences 290:1-2, 16-21
CrossRef23
Yung-Bin Kuo, C. Allen Chang, Yao-Kuang Wu, Meng-Jer Hsieh, Chung-Hsien Tsai, Kuei-Tien Chen, Chun-Yu Chen, Err-Cheng Chan. (2010) Identification and clinical association of anti-cytokeratin 18 autoantibody in COPD. Immunology Letters 128:2, 131-136
CrossRef24
Johannes Brettschneider, Troy D. Jaskowski, Hayrettin Tumani, Sana Abdul, Dee Husebye, Haniah Seraj, Harry R. Hill, Ella Fire, Larissa Spector, Jennifer Yarden, Nir Dotan, John W. Rose. (2009) Serum anti-GAGA4 IgM antibodies differentiate relapsing remitting and secondary progressive multiple sclerosis from primary progressive multiple sclerosis and other neurological diseases. Journal of Neuroimmunology 217:1-2, 95-101
CrossRef25
Fabienne Brilot, Russell C. Dale, Rebecca C. Selter, Verena Grummel, Sudhakar Reddy Kalluri, Muhammad Aslam, Verena Busch, Dun Zhou, Sabine Cepok, Bernhard Hemmer. (2009) Antibodies to native myelin oligodendrocyte glycoprotein in children with inflammatory demyelinating central nervous system disease. Annals of Neurology 66:6, 833-842
CrossRef26
Yoh Matsumoto, Il-Kwon Park, Keiko Hiraki, Shin Ohtani, Kuniko Kohyama. (2009) Role of pathogenic T cells and autoantibodies in relapse and progression of myelin oligodendrocyte glycoprotein-induced autoimmune encephalomyelitis in LEW.1AV1 rats. Immunology 128:1pt2, e250-e261
CrossRef27
Chris J. Hedegaard, Ning Chen, Finn Sellebjerg, Per Soelberg Sørensen, R. Graham Q. Leslie, Klaus Bendtzen, Claus H. Nielsen. (2009) Autoantibodies to myelin basic protein (MBP) in healthy individuals and in patients with multiple sclerosis: a role in regulating cytokine responses to MBP. Immunology 128:1pt2, e451-e461
CrossRef28
Maya N. Hatch, Chris S. Schaumburg, Thomas E. Lane, Hans S. Keirstead. (2009) Endogenous remyelination is induced by transplant rejection in a viral model of multiple sclerosis. Journal of Neuroimmunology 212:1-2, 74-81
CrossRef29
Gregory P. Owens, Jeffrey L. Bennett, Hans Lassmann, Kevin C. O'Connor, Alanna M. Ritchie, Andrew Shearer, Chiwah Lam, Xiaoli Yu, Marius Birlea, Cecily DuPree, R. Anthony Williamson, David A. Hafler, Mark P. Burgoon, Don Gilden. (2009) Antibodies produced by clonally expanded plasma cells in multiple sclerosis cerebrospinal fluid. Annals of Neurology 65:6, 639-649
CrossRef30
Jeffrey L. Bennett, Olaf Stüve. (2009) Update on Inflammation, Neurodegeneration, and Immunoregulation in Multiple Sclerosis. Clinical Neuropharmacology 32:3, 121-132
CrossRef31
Bert A. 't Hart, Luca Massacesi. (2009) Clinical, Pathological, and Immunologic Aspects of the Multiple Sclerosis Model in Common Marmosets (Callithrix jacchus). Journal of Neuropathology and Experimental Neurology 68:4, 341-355
CrossRef32
Yukio Sekiguchi, Motoki Ichikawa, Masaya Takamoto, Hiroyoshi Ota, Chang-Sung Koh, Masamichi Muramatsu, Tasuku Honjo, Kazunaga Agematsu. (2009) Antibodies to myelin oligodendrocyte glycoprotein are not involved in the severity of chronic non-remitting experimental autoimmune encephalomyelitis. Immunology Letters 122:2, 145-149
CrossRef33
M. Rafei, J. Hsieh, S. Fortier, M. Li, S. Yuan, E. Birman, K. Forner, M.-N. Boivin, K. Doody, M. Tremblay, B. Annabi, J. Galipeau. (2008) Mesenchymal stromal cell-derived CCL2 suppresses plasma cell immunoglobulin production via STAT3 inactivation and PAX5 induction. Blood 112:13, 4991-4998
CrossRef34
F. J. Quintana, M. F. Farez, V. Viglietta, A. H. Iglesias, Y. Merbl, G. Izquierdo, M. Lucas, A. S. Basso, S. J. Khoury, C. F. Lucchinetti, I. R. Cohen, H. L. Weiner. (2008) Antigen microarrays identify unique serum autoantibody signatures in clinical and pathologic subtypes of multiple sclerosis. Proceedings of the National Academy of Sciences 105:48, 18889-18894
CrossRef35
Hans Lassmann. (2008) Mechanisms of inflammation induced tissue injury in multiple sclerosis. Journal of the Neurological Sciences 274:1-2, 45-47
CrossRef36
Christian Confavreux, Sandra Vukusic. (2008) The Clinical Epidemiology of Multiple Sclerosis. Neuroimaging Clinics of North America 18:4, 589-622
CrossRef37
, H. Wiendl, K. V. Toyka, P. Rieckmann, R. Gold, H.-P. Hartung, R. Hohlfeld. (2008) Basic and escalating immunomodulatory treatments in multiple sclerosis: Current therapeutic recommendations. Journal of Neurology 255:10, 1449-1463
CrossRef38
Christopher T. Harp, Amy E. Lovett-Racke, Michael K. Racke, Elliot M. Frohman, Nancy L. Monson. (2008) Impact of myelin-specific antigen presenting B cells on T cell activation in multiple sclerosis. Clinical Immunology 128:3, 382-391
CrossRef39
J.-C. Corvol, D. Pelletier, R. G. Henry, S. J. Caillier, J. Wang, D. Pappas, S. Casazza, D. T. Okuda, S. L. Hauser, J. R. Oksenberg, S. E. Baranzini. (2008) Abrogation of T cell quiescence characterizes patients at high risk for multiple sclerosis after the initial neurological event. Proceedings of the National Academy of Sciences 105:33, 11839-11844
CrossRef40
Hans‐Christian von Büdingen, Melanie D. Harrer, Sandra Kuenzle, Mirjam Meier, Norbert Goebels. (2008) Clonally expanded plasma cells in the cerebrospinal fluid of MS patients produce myelin‐specific antibodies. European Journal of Immunology 38:7, 2014-2023
CrossRef41
Nuhad Abou Zeid, M Tariq Bhatti. (2008) Acute Inflammatory Demyelinating Optic Neuritis. The Neurologist 14:4, 207-223
CrossRef42
Alfonso Ramunni, Francesca De Robertis, Paola Brescia, Maria Teresa Saliani, Michele Amoruso, Maria Prontera, Elena Dimonte, Maria Trojano, Pasquale Coratelli. (2008) A Case Report of Double Filtration Plasmapheresis in an Acute Episode of Multiple Sclerosis. Therapeutic Apheresis and Dialysis 12:3, 250-254
CrossRef43
Aristo Vojdani. (2008) Antibodies as predictors of autoimmune diseases and cancer. Expert Opinion on Medical Diagnostics 2:6, 593-605
CrossRef44
S. Anwar Jagessar, Paul A. Smith, Erwin Blezer, Cecile Delarasse, Danielle Pham-Dinh, Jon D. Laman, Jan Bauer, Sandra Amor, Bert 't Hart. (2008) Autoimmunity Against Myelin Oligodendrocyte Glycoprotein Is Dispensable for the Initiation Although Essential for the Progression of Chronic Encephalomyelitis in Common Marmosets. Journal of Neuropathology and Experimental Neurology 67:4, 326-340
CrossRef45
Stephanie C. Joachim, Jan Reichelt, Simone Berneiser, Norbert Pfeiffer, Franz H. Grus. (2008) Sera of glaucoma patients show autoantibodies against myelin basic protein and complex autoantibody profiles against human optic nerve antigens. Graefe's Archive for Clinical and Experimental Ophthalmology 246:4, 573-580
CrossRef46
Stéphane Roche, Audrey Gabelle, Sylvain Lehmann. (2008) Clinical proteomics of the cerebrospinal fluid: Towards the discovery of new biomarkers. PROTEOMICS – CLINICAL APPLICATIONS 2:3, 428-436
CrossRef47
Sangjin Oh, Cornelia Cudrici, Takahiro Ito, Horea Rus. (2008) B-cells and humoral immunity in multiple sclerosis. Implications for therapy. Immunologic Research 40:3, 224-234
CrossRef48
Matthias Mehling, Jens Kuhle, Axel Regeniter. (2008) 10 Most Commonly Asked Questions About Cerebrospinal Fluid Characteristics in Demyelinating Disorders of the Central Nervous System. The Neurologist 14:1, 60-65
CrossRef49
Samantha Jilek, Jens Kuhle, Pascal Meylan, Marc D. Reichhart, Giuseppe Pantaleo, Renaud A. Du Pasquier. (2007) Severe post-EBV encephalopathy associated with myelin oligodendrocyte glycoprotein-specific immune response. Journal of Neuroimmunology 192:1-2, 192-197
CrossRef50
R. Gold, P. Rieckmann. (2007) Fortschritte im Verständnis von Pathogenese und Immuntherapie der Multiplen Sklerose. Der Nervenarzt 78:S1, 15-26
CrossRef51
I. Greeve, J. Sellner, T. Lauterburg, U. Walker, K. M. Rösler, H. P. Mattle. (2007) Anti-myelin antibodies in clinically isolated syndrome indicate the risk of multiple sclerosis in a Swiss cohort. Acta Neurologica Scandinavica 116:4, 207-210
CrossRef52
Andrew R. Pachner, Jennifer Brady, Kavitha Narayan. (2007) Antibody-secreting cells in the central nervous system in an animal model of MS: Phenotype, association with disability, and in vitro production of antibody. Journal of Neuroimmunology 190:1-2, 112-120
CrossRef53
Bettina Kuenz, Florian Deisenhammer, Thomas Berger, Markus Reindl. (2007) Diagnostic biomarkers in multiple sclerosis. Expert Opinion on Medical Diagnostics 1:2, 225-233
CrossRef54
Michele Fiorini, Gianluigi Zanusso, Maria Donata Benedetti, Pier Giorgio Righetti, Salvatore Monaco. (2007) Cerebrospinal fluid biomarkers in clinically isolated syndromes and multiple sclerosis. PROTEOMICS – CLINICAL APPLICATIONS 1:9, 963-971
CrossRef55
Henry F McFarland, Roland Martin. (2007) Multiple sclerosis: a complicated picture of autoimmunity. Nature Immunology 8:9, 913-919
CrossRef56
Thomas Berger, Markus Reindl. (2007) Multiple sclerosis: Disease biomarkers as indicated by pathophysiology. Journal of the Neurological Sciences 259:1-2, 21-26
CrossRef57
R. Schneider, B. Euler, S. Rauer. (2007) Intrathecal IgM-synthesis does not correlate with the risk of relapse in patients with a primary demyelinating event. European Journal of Neurology 14:8, 907-911
CrossRef58
C. Kleinschnitz, S.G. Meuth, B.C. Kieseier, H. Wiendl. (2007) Multiple-Sklerose-Update zur Pathophysiologie und neuen immuntherapeutischen Ansätzen. Der Nervenarzt 78:8, 883-911
CrossRef59
Simon Fillatreau, Stephen M Anderton. (2007) B-cell function in CNS inflammatory demyelinating disease: a complexity of roles and a wealth of possibilities. Expert Review of Clinical Immunology 3:4, 565-578
CrossRef60
Claus H Nielsen, Daniel El Fassi, Hans C Hasselbalch, Klaus Bendtzen, Laszlo Hegedüs. (2007) B-cell depletion with rituximab in the treatment of autoimmune diseases. Expert Opinion on Biological Therapy 7:7, 1061-1078
CrossRef61
Dean M Wingerchuk, Claudia F Lucchinetti. (2007) Comparative immunopathogenesis of acute disseminated encephalomyelitis, neuromyelitis optica, and multiple sclerosis. Current Opinion in Neurology 20:3, 343-350
CrossRef62
Nicola Bizzaro. (2007) Autoantibodies as predictors of disease: The clinical and experimental evidence. Autoimmunity Reviews 6:6, 325-333
CrossRef63
(2007) Lack of Association between Antimyelin Antibodies and Progression to Multiple Sclerosis. New England Journal of Medicine 356:18, 1888-1889
Full Text64
Eric C. Klawiter, Anne H. Cross. (2007) B cells: No longer the nondominant arm of multiple sclerosis. Current Neurology and Neuroscience Reports 7:3, 231-238
CrossRef65
Doris Lambracht-Washington, Kevin C. O'Connor, Elizabeth M. Cameron, Andrea Jowdry, E. Sally Ward, Elliot Frohman, Michael K. Racke, Nancy L. Monson. (2007) Antigen specificity of clonally expanded and receptor edited cerebrospinal fluid B cells from patients with relapsing remitting MS. Journal of Neuroimmunology 186:1-2, 164-176
CrossRef66
H. Onoue, J.-I. Satoh, M. Ogawa, H. Tabunoki, T. Yamamura. (2007) Detection of anti-Nogo receptor autoantibody in the serum of multiple sclerosis and controls. Acta Neurologica Scandinavica 115:3, 153-160
CrossRef67
Jens Kuhle, Raija L.P. Lindberg, Axel Regeniter, Matthias Mehling, Francine Hoffmann, Markus Reindl, Thomas Berger, Ernst W. Radue, David Leppert, Ludwig Kappos. (2007) Antimyelin antibodies in clinically isolated syndromes correlate with inflammation in MRI and CSF. Journal of Neurology 254:2, 160-168
CrossRef68
Kevin C O'Connor, Katherine A McLaughlin, Philip L De Jager, Tanuja Chitnis, Estelle Bettelli, Chenqi Xu, William H Robinson, Sunil V Cherry, Amit Bar-Or, Brenda Banwell, Hikoaki Fukaura, Toshiyuki Fukazawa, Silvia Tenembaum, Susan J Wong, Norma P Tavakoli, Zhannat Idrissova, Vissia Viglietta, Kevin Rostasy, Daniela Pohl, Russell C Dale, Mark Freedman, Lawrence Steinman, Guy J Buckle, Vijay K Kuchroo, David A Hafler, Kai W Wucherpfennig. (2007) Self-antigen tetramers discriminate between myelin autoantibodies to native or denatured protein. Nature Medicine 13:2, 211-217
CrossRef69
H. C. Lehmann, Hans-Peter Hartung, G. R. Hetzel, B. C. Kieseier. (2007) Plasmaaustausch als Therapieoption bei neurologischen Erkrankungen. Der Nervenarzt 78:2, 166-176
CrossRef70
Cécile Cassan, Roland S. Liblau. (2007) Immune tolerance and control of CNS autoimmunity: from animal models to MS patients. Journal of Neurochemistry 100:4, 883-892
CrossRef71
Pelayo, Raul, Tintoré, Mar, Montalban, Xavier, Rovira, Alex, Espejo, Carmen, , Reindl, Markus, Berger, Thomas, . (2007) Antimyelin Antibodies with No Progression to Multiple Sclerosis. New England Journal of Medicine 356:4, 426-428
Full Text72
Kuhle, Jens, Pohl, Christoph, Mehling, Matthias, Edan, Gilles, Freedman, Mark S., Hartung, Hans-Peter, Polman, Chris H., Miller, David H., Montalban, Xavier, Barkhof, Frederik, Bauer, Lars, Dahms, Susanne, Lindberg, Raija, Kappos, Ludwig, Sandbrink, Rupert, . (2007) Lack of Association between Antimyelin Antibodies and Progression to Multiple Sclerosis. New England Journal of Medicine 356:4, 371-378
Full Text73
Ivana Zadro, Vesna Brinar, Gordana Horvat, Marko Brinar. (2007) Clinical relevance of antibodies against myelin oligodendrocyte glycoprotein in different clinical types of multiple sclerosis. Clinical Neurology and Neurosurgery 109:1, 23-26
CrossRef74
, Peter Rieckmann. (2006) Immunmodulatorische Stufentherapie der Multiplen Sklerose. Der Nervenarzt 77:12, 1506-1518
CrossRef75
Anne H. Cross, Jennifer L. Stark, Joanne Lauber, Michael J. Ramsbottom, Jeri-Anne Lyons. (2006) Rituximab reduces B cells and T cells in cerebrospinal fluid of multiple sclerosis patients. Journal of Neuroimmunology 180:1-2, 63-70
CrossRef76
Daniel D. Mikol, Charles Ditlow, Danielle Usatin, Pinaki Biswas, Jack Kalbfleisch, Andrew Milner, Emanuel Calenoff. (2006) Serum IgE reactive against small myelin protein-derived peptides is increased in multiple sclerosis patients. Journal of Neuroimmunology 180:1-2, 40-49
CrossRef77
Jack Antel, Amit Bar-Or. (2006) Roles of immunoglobulins and B cells in multiple sclerosis: From pathogenesis to treatment. Journal of Neuroimmunology 180:1-2, 3-8
CrossRef78
Markus Reindl, Michael Khalil, Thomas Berger. (2006) Antibodies as biological markers for pathophysiological processes in MS. Journal of Neuroimmunology 180:1-2, 50-62
CrossRef79
2006. Multiple Sclerosis. .
CrossRef80
D. Buck, A. Kroner, P. Rieckmann, M. Mäurer, H. Wiendl. (2006) Analysis of the C/T ?1 single nucleotide polymorphism in the CD40 gene in multiple sclerosis. Tissue Antigens 68:4, 335-338
CrossRef81
Marinos C. Dalakas. (2006) B cells in the pathophysiology of autoimmune neurological disorders: A credible therapeutic target. Pharmacology & Therapeutics 112:1, 57-70
CrossRef82
Helene Zephir, Lionel Almeras, Mohamed El Behi, Patricia Dussart, Jerome de Seze, Jerome Steibel, Elizabeth Trifilieff, Sylvain Dubucquoi, Jean-Paul Dessaint, Patrick Vermersch, Lionel Prin, Didier Lefranc. (2006) Diversified serum IgG response involving non-myelin CNS proteins during experimental autoimmune encephalomyelitis. Journal of Neuroimmunology 179:1-2, 53-64
CrossRef83
K. G. Warren, I. Catz, L. Z. Ferenczi, M. J. Krantz. (2006) Intravenous synthetic peptide MBP8298 delayed disease progression in an HLA Class II-defined cohort of patients with progressive multiple sclerosis: results of a 24-month double-blind placebo-controlled clinical trial and 5 years of follow-up treatment. European Journal of Neurology 13:8, 887-895
CrossRef84
Scott R. Barnum, Alexander J. Szalai. (2006) Complement and demyelinating disease: No MAC needed?. Brain Research Reviews 52:1, 58-68
CrossRef85
Esther C.W. Breij, Priscilla Heijnen, Annette van der Goes, Charlotte E. Teunissen, Chris H. Polman, Christine D. Dijkstra. (2006) Myelin flow cytometry assay detects enhanced levels of antibodies to human whole myelin in a subpopulation of multiple sclerosis patients. Journal of Neuroimmunology 176:1-2, 106-114
CrossRef86
Jeffrey L. Browning. (2006) B cells move to centre stage: novel opportunities for autoimmune disease treatment. Nature Reviews Drug Discovery 5:7, 564-576
CrossRef87
Veda L Tsoi, Kenneth E Hill, Noel G Carlson, Judith E. A Warner, John W Rose. (2006) Immunohistochemical Evidence of Inducible Nitric Oxide Synthase and Nitrotyrosine in a Case of Clinically Isolated Optic Neuritis. Journal of Neuro-Ophthalmology 26:2, 87-94
CrossRef88
O. Torkildsen, C. A. Vedeler, H. I. Nyland, K.-M. Myhr. (2006) FcgammaR and multiple sclerosis: an overview. Acta Neurologica Scandinavica 113:s183, 61-63
CrossRef89
Mikael Schwarz, Larissa Spector, Monica Gortler, Oori Weisshaus, Lea Glass-Marmor, Arnon Karni, Nir Dotan, Ariel Miller. (2006) Serum anti-Glc(α1,4)Glc(α) antibodies as a biomarker for relapsing–remitting multiple sclerosis. Journal of the Neurological Sciences 244:1-2, 59-68
CrossRef90
Michael Khalil, Markus Reindl, Andreas Lutterotti, Bettina Kuenz, Rainer Ehling, Claudia Gneiss, Peter Lackner, Florian Deisenhammer, Thomas Berger. (2006) Epitope specificity of serum antibodies directed against the extracellular domain of myelin oligodendrocyte glycoprotein: Influence of relapses and immunomodulatory treatments. Journal of Neuroimmunology 174:1-2, 147-156
CrossRef91
Francesco Lolli, Paolo Rovero, Mario Chelli, Anna Maria Papini. (2006) Toward biomarkers in multiple sclerosis: new advances. Expert Review of Neurotherapeutics 6:5, 781-794
CrossRef92
H.-Christian Büdingen, Til Menge, Stephen L. Hauser, Claude P. Genain. (2006) Restrictive and diversifying elements of the anti-myelin/oligodendrocyte glycoprotein antibody response in primate experimental allergic encephalomyelitis. Immunogenetics 58:2-3, 122-128
CrossRef93
Gregory P. Owens, Jeffrey L. Bennett, Donald H. Gilden, Mark P. Burgoon. (2006) The B cell response in multiple sclerosis. Neurological Research 28:3, 236-244
CrossRef94
Edward A. Greenfield, Jayagopala Reddy, Andrew Lees, Charissa A. Dyer, Omanand Koul, Khuong Nguyen, Shannon Bell, Nasim Kassam, Julian Hinojoza, Mary Jane Eaton, Marjorie B. Lees, Vijay K. Kuchroo, Raymond A. Sobel. (2006) Monoclonal antibodies to distinct regions of human myelin proteolipid protein simultaneously recognize central nervous system myelin and neurons of many vertebrate species. Journal of Neuroscience Research 83:3, 415-431
CrossRef95
Natalia A. Ponomarenko, Oxana M. Durova, Ivan I. Vorobiev, Alexey A. Belogurov, Georgy B. Telegin, Sergey V. Suchkov, Victor K. Misikov, Herbert C. Morse, Alexander G. Gabibov. (2006) Catalytic activity of autoantibodies toward myelin basic protein correlates with the scores on the multiple sclerosis expanded disability status scale. Immunology Letters 103:1, 45-50
CrossRef96
David Pleasure, Athena Soulika, Sunit K. Singh, Vittorio Gallo, Peter Bannerman. (2006) Inflammation in white matter: Clinical and pathophysiological aspects. Mental Retardation and Developmental Disabilities Research Reviews 12:2, 141-146
CrossRef97
D. Karussis, L. D. Biermann, S. Bohlega, A. Boiko, M. Chofflon, F. Fazekas, M. Freedman, S. Gebeily, R. Gouider, E. Havrdova, G. Jakab, R. Karabudak, A. Miller, . (2006) A recommended treatment algorithm in relapsing multiple sclerosis: report of an international consensus meeting. European Journal of Neurology 13:1, 61-71
CrossRef98
Maria Claudia Alcaro, Anna Maria Papini. (2006) Contribution of peptides to multiple sclerosis research. Biopolymers 84:4, 349-367
CrossRef99
Hans-Peter Hartung, Bernd C. Kieseier, Bernhard Hemmer. (2005) Purely systemically active anti-inflammatory treatments are adequate to control multiple sclerosis. Journal of Neurology 252:S5, v30-v37
CrossRef100
Diego Franciotta, Carlo Avolio, Elisabetta Capello, Francesco Lolli. (2005) Consensus recommendations of the Italian Association for Neuroimmunology for immunochemical cerebrospinal fluid examination. Journal of the Neurological Sciences 237:1-2, 5-11
CrossRef101
Ø. Torkildsen, C.A. Vedeler, E. Ulvestad, J.H. Aarseth, H.I. Nyland, K.-M. Myhr. (2005) High dose methylprednisolone induces FcγRI on granulocytes in MS-patients. Journal of Neuroimmunology 167:1-2, 138-142
CrossRef102
Francesco Lolli, Benedetta Mazzanti, Marta Pazzagli, Elisa Peroni, Maria Claudia Alcaro, Giuseppina Sabatino, Roberta Lanzillo, Vincenzo Brescia Morra, Lucio Santoro, Claudio Gasperini, Stefania Galgani, Mario Milco D'Elios, Valentina Zipoli, Stefano Sotgiu, Maura Pugliatti, Paolo Rovero, Mario Chelli, Anna Maria Papini. (2005) The glycopeptide CSF114(Glc) detects serum antibodies in multiple sclerosis. Journal of Neuroimmunology 167:1-2, 131-137
CrossRef103
S. Schwarz, M. Knauth, B. Storch-Hagenlocher. (2005) Akute disseminierte Enzephalomyelitis (ADEM). Intensivmedizin und Notfallmedizin 42:6, 496-509
CrossRef104
Tjalf Ziemssen, Focke Ziemssen. (2005) The role of the humoral immune system in multiple sclerosis (MS) and its animal model experimental autoimmune encephalomyelitis (EAE). Autoimmunity Reviews 4:7, 460-467
CrossRef105
Hans-Peter Hartung. (2005) Early treatment and dose optimisation. Journal of Neurology 252:S3, iii44-iii50
CrossRef106
Ludwig Kappos, Lutz Achtnichts, Frank Dahlke, Jens Kuhle, Y. Naegelin, Rupert Sandbrink, Raija L. P. Lindberg. (2005) Genomics and proteomics: role in the management of multiple sclerosis. Journal of Neurology 252:S3, iii21-iii27
CrossRef107
Wolfgang Hueber, Brian A. Kidd, Beren H. Tomooka, Byung J. Lee, Bonnie Bruce, James F. Fries, Grete Sønderstrup, Paul Monach, Jan W. Drijfhout, Walther J. van Venrooij, Paul J. Utz, Mark C. Genovese, William H. Robinson. (2005) Antigen microarray profiling of autoantibodies in rheumatoid arthritis. Arthritis & Rheumatism 52:9, 2645-2655
CrossRef108
Mark Keegan, Fatima König, Robyn McClelland, Wolfgang Brück, Yazmín Morales, Andreas Bitsch, Hillel Panitch, Hans Lassmann, Brian Weinshenker, Moses Rodriguez, Joseph Parisi, Claudia F Lucchinetti. (2005) Relation between humoral pathological changes in multiple sclerosis and response to therapeutic plasma exchange. The Lancet 366:9485, 579-582
CrossRef109
A. Moldenhauer, J. Haas, C. Wascher, T. Derfuss, K.-T. Hoffmann, H. Kiesewetter, A. Salama. (2005) Immunoadsorption patients with multiple sclerosis: an open-label pilot study. European Journal of Clinical Investigation 35:8, 523-530
CrossRef110
Bernd C Kieseier, Bernhard Hemmer, Hans-Peter Hartung. (2005) Multiple sclerosis – novel insights and new therapeutic strategies. Current Opinion in Neurology 18:3, 211-220
CrossRef111
Ee Tuan Lim, Gavin Giovannoni. (2005) Immunopathogenesis and immunotherapeutic approaches in multiple sclerosis. Expert Review of Neurotherapeutics 5:3, 379-390
CrossRef112
David Miller, Frederik Barkhof, Xavier Montalban, Alan Thompson, Massimo Filippi. (2005) Clinically isolated syndromes suggestive of multiple sclerosis, part I: natural history, pathogenesis, diagnosis, and prognosis. The Lancet Neurology 4:5, 281-288
CrossRef113
Babs O. Fabriek, Jack N.P. Zwemmer, Charlotte E. Teunissen, Christine D. Dijkstra, Chris H. Polman, Jon D. Laman, Jonas A. Castelijns. (2005) In vivo detection of myelin proteins in cervical lymph nodes of MS patients using ultrasound-guided fine-needle aspiration cytology. Journal of Neuroimmunology 161:1-2, 190-194
CrossRef114
Mireia Sospedra, Roland Martin. (2005) IMMUNOLOGY OF MULTIPLE SCLEROSIS*. Annual Review of Immunology 23:1, 683-747
CrossRef115
David A. Hafler, Jacqueline M. Slavik, David E. Anderson, Kevin C. O'Connor, Philip De Jager, Clare Baecher-Allan. (2005) Multiple sclerosis. Immunological Reviews 204:1, 208-231
CrossRef116
T. Magnus, M. S. Rao. (2005) Neural stem cells in inflammatory CNS diseases: mechanisms and therapy. Journal of Cellular and Molecular Medicine 9:2, 303-319
CrossRef117
KELLY A BENNETT. (2005) Pregnancy and Multiple Sclerosis. Clinical Obstetrics and Gynecology 48:1, 38-47
CrossRef118
Corrado Betterle, Graziella Coco, Renato Zanchetta. (2005) Adrenal cortex autoantibodies in subjects with normal adrenal function. Best Practice & Research Clinical Endocrinology & Metabolism 19:1, 85-99
CrossRef119
Taeg S. Kim, Stanley Perlman. (2005) Virus-Specific Antibody, in the Absence of T Cells, Mediates Demyelination in Mice Infected with a Neurotropic Coronavirus. The American Journal of Pathology 166:3, 801-809
CrossRef120
Stephen L. Hauser. (2005) An update on multiple sclerosis. Journal of the Neurological Sciences 228:2, 193-194
CrossRef121
Amit Bar-Or. (2005) Immunology of multiple sclerosis. Neurologic Clinics 23:1, 149-175
CrossRef122
Elliot M Frohman, Teresa C Frohman, David S Zee, Roderick McColl, Steven Galetta. (2005) The neuro-ophthalmology of multiple sclerosis. The Lancet Neurology 4:2, 111-121
CrossRef123
Richard H. Quarles. (2005) Comparison of CNS and PNS myelin proteins in the pathology of myelin disorders. Journal of the Neurological Sciences 228:2, 187-189
CrossRef124
Claudia F. Lucchinetti, Joseph Parisi, Wolfgang Bruck. (2005) The pathology of multiple sclerosis. Neurologic Clinics 23:1, 77-105
CrossRef125
Mohamed El Behi, Sylvain Dubucquoi, Didier Lefranc, Hélène Zéphir, Jérome De Seze, Patrick Vermersch, Lionel Prin. (2005) New insights into cell responses involved in experimental autoimmune encephalomyelitis and multiple sclerosis. Immunology Letters 96:1, 11-26
CrossRef126
Paulo Fontoura, Hideki Garren, Lawrence Steinman. (2005) Antigen-Specific Therapies in Multiple Sclerosis: Going Beyond Proteins and Peptides. International Reviews of Immunology 24:5-6, 415-446
CrossRef127
A. Chan, F. X. Weilbach, K. V. Toyka, R. Gold. (2005) Mitoxantrone induces cell death in peripheral blood leucocytes of multiple sclerosis patients. Clinical and Experimental Immunology 139:1, 152-158
CrossRef128
William A Sheremata, Alireza Minagar, J Steven Alexander, Timothy Vollmer. (2005) The Role of Alpha-4 Integrin in the Aetiology of Multiple Sclerosis. CNS Drugs 19:11, 909-922
CrossRef129
Jan Storek, Zhao Zhao, Eugene Lin, Thomas Berger, Peter A. McSweeney, Richard A. Nash, Yoshiki Akatsuka, Monja D. Metcalf, Hailing Lu, Tomas Kalina, Markus Reindl, Rainer Storb, John A. Hansen, Keith M. Sullivan, George H. Kraft, Daniel E. Furst, David G. Maloney. (2004) Recovery from and consequences of severe iatrogenic lymphopenia (induced to treat autoimmune diseases). Clinical Immunology 113:3, 285-298
CrossRef130
Bert A 't Hart, Jon D Laman, Jan Bauer, Erwin Blezer, Yvette van Kooyk, Rogier Q Hintzen. (2004) Modelling of multiple sclerosis: lessons learned in a non-human primate. The Lancet Neurology 3:10, 588-597
CrossRef131
Thomas Berger, Markus Reindl. (2004) Immunpathogenetische Subtypisierung der Multiplen Sklerose / Immunopathogenetic subtyping of multiple sclerosis. LaboratoriumsMedizin 28:5, 424-430
CrossRef132
Marc Tardieu, Yann Mikaeloff. (2004) What is acute disseminated encephalomyelitis (ADEM)?. European Journal of Paediatric Neurology 8:5, 239-242
CrossRef133
, , . (2004) What do we know about the mechanism of action of disease-modifying treatments in MS?. Journal of Neurology 251:S5, v12-v29
CrossRef134
Enrique Montero, Gabriel Nussbaum, Joel F Kaye, Rolando Perez, Agustin Lage, Avraham Ben-Nun, Irun R Cohen. (2004) Regulation of experimental autoimmune encephalomyelitis by CD4+, CD25+ and CD8+ T cells: analysis using depleting antibodies. Journal of Autoimmunity 23:1, 1-7
CrossRef135
Tara Karnezis, Wim Mandemakers, Jonathan L McQualter, Binhai Zheng, Peggy P Ho, Kelly A Jordan, Belinda M Murray, Ben Barres, Marc Tessier-Lavigne, Claude C A Bernard. (2004) The neurite outgrowth inhibitor Nogo A is involved in autoimmune-mediated demyelination. Nature Neuroscience 7:7, 736-744
CrossRef136
Tony Waegemans. (2004) Auto-antibodies in multiple sclerosis: an hypothesis. Biomedicine & Pharmacotherapy 58:5, 282-285
CrossRef137
Lorinda Chung, Paul J. Utz. (2004) Antibodies in scleroderma: Direct pathogenicity and phenotypic associations. Current Rheumatology Reports 6:2, 156-163
CrossRef138
David H. Miller. (2004) Biomarkers and surrogate outcomes in neurodegenerative disease: Lessons from multiple sclerosis. NeuroRX 1:2, 284-294
CrossRef139
Alexander J. Szalai, Scott R. Barnum. (2004) Fc receptors and the common ?-chain in experimental autoimmune encephalomyelitis. Journal of Neuroscience Research 75:5, 597-602
CrossRef140
David H. Miller. (2004) Biomarkers and surrogate outcomes in neurodegenerative disease: Lessons from multiple sclerosis. NeuroRX 1:2, 284
CrossRef141
Robert J Fox, Richard A Rudick. (2004) Multiple sclerosis: disease markers accelerate progress. The Lancet Neurology 3:1, 10
CrossRef142
(2003) Antimyelin Antibodies in Multiple Sclerosis. New England Journal of Medicine 349:23, 2269-2271
Full Text143
Paula Moyer. (2003) MS. Neurology Today 3:12, 7-8
CrossRef144
David F. Keren. (2003) Optimizing Detection of Oligoclonal Bands in Cerebrospinal Fluid by Use of Isoelectric Focusing With IgG Immunoblotting. American Journal of Clinical Pathology 120:5, 649-651
CrossRef145
Neil Scolding. (2003) First attack in multiple sclerosis: harbinger or history?. The Lancet Neurology 2:9, 526
CrossRef146
Antel, Jack P., Bar-Or, Amit, . (2003) Do Myelin-Directed Antibodies Predict Multiple Sclerosis?. New England Journal of Medicine 349:2, 107-109
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