AntiBodies Against Myelin Oligodendrocyte Glycoprotein In The CerebroSpinal Fluid Of Multiple Sclerosis Patients
Markovic M, Trajkovic V, Drulovic J, Mesaros S, Stojsavljevic N, Dujmovic I, Mostarica Stojkovic M
J Neurol Sci 2003 Jul 15;211(1-2):67-73
University of Belgrade, Institute of MicroBiology and Immunology, School of Medicine, Dr. Subotica 1, Belgrade 11000, Yugoslavia
AntiBodies against Myelin Oligodendrocyte Glycoprotein (MOG) mediate DeMyelination in Experimental Autoimmune Encephalomyelitis (EAE) in different animal species and are implicated in the ImmunoPathogenesis of Multiple Sclerosis (MS).
In order to evaluate the AntiMOG response, we have analyzed the CerebroSpinal Fluids (CSFs) from 44 MS patients and 51 controls, 11 with Other Inflammatory Neurological Disorders (OIND) and 40 with Non-Inflammatory Neurological Disorders (NIND).
The frequency of Anti-MOG AntiBodies positive patients in the MS group (30%) was significantly higher compared to the NIND (8%, p=0.02), but not compared to the OIND group (55%, p=0.228).
Interestingly, all six patients with NeuroSarcoidosis had MOG-specific AntiBodies in their CSF. Frequency of Anti-MOG AntiBodies was similar in patients with clinically active and stable MS (32% and 26%, respectively; p=0.921).
However, in clinically active MS patients, AntiBody Titers were higher in comparison with patients with stable disease, although the difference did not reach the level of statistical significance (p=0.06).
These results further support the potential role of Anti-MOG AntiBodies in the ImmunoPathology of MS in the subset of patients with this disease.
Furthermore, our findings suggest for the first time that Anti-MOG AntiBodies could be an accessory diagnostic tool in NeuroSarcoidosis.
Intrathecal B-Cell Clonal Expansion, An Early Sign Of Humoral Immunity, In The CerebroSpinal Fluid Of Patients With Clinically Isolated Syndrome Suggestive Of Multiple Sclerosis
Qin Y, Duquette P, Zhang Y, Olek M, Da RR, Richardson J, Antel JP, Talbot P, Cashman NR, Tourtellotte WW, Wekerle H, Van Den Noort S
Lab Invest 2003 Jul;83(7):1081-8
University of California Irvine, Department of Neurology, Irvine, California 92697, USA
The development of somatically mutated Memory and Plasma B-Cells is a consequence of T-Cell-dependent Antigen-challenged Humoral Immunity.
To investigate the role of B-Cell-mediated Humoral Immunity in the initiation and evolution of Multiple Sclerosis (MS), we analyzed Ig variable heavy chain genes of Intrathecal B-Cells derived from patients with a first clinical manifestation suggestive of MS.
Sequences of Ig variable regions showed that B-Cells in the CerebroSpinal Fluid from most of these patients were clonally expanded and carried somatic hypermutated variable heavy chain genes.
The mutations showed a high replacement-to-silent ratio and were distributed in a way suggesting that these clonally expanded B-Cells had been positively selected through their Antigen Receptor.
In comparison, Intrathecal B-Cell clonal expansion often precedes both OligoClonal IgG Bands and multiple Magnetic Resonance Imaging lesions.
Clinical follow-up study showed that patients with clonally expanded Intrathecal B-Cells had a high rate of conversion to Clinically Definite MS.
The findings provide direct evidence of recruitment of germinal center differentiated B-Lymphocytes into the Central Nervous System during the initiation of MS.
These results indicate B-Cell-mediated Immune Response in the CerebroSpinal Fluid is an early event of inflammatory reaction in the Central Nervous System of MS.
This procedure also provides a more sensitive method to evaluate the association of Humoral Immunity in the evolution of MS.
Skewed AutoAntiBody Reactivity To The Extracellular Domain Of Myelin Oligodendrocyte Glycoprotein In Multiple Sclerosis
Tejada-Simon MV, Hong J, Rivera VM, Zhang JZ
Immunology 2002 Dec;107(4):403-10
Baylor College of Medicine, Multiple Sclerosis Research Unit, Baylor-Methodist Multiple Sclerosis Center and Department of Neurology, Houston, Texas 77030, USA
Myelin Oligodendrocyte Glycoprotein (MOG) is found to induce both AutoReactive T-Cell and AntiBody responses associated with DeMyelinating pathology and is implicated in the pathogenesis of Multiple Sclerosis (MS).
In this study, we addressed the potential association of Anti-MOG Immune Responses with MS by examining, comparatively, both the T-Cell and AntiBody responses to recombinant MOG fragments in MS patients and healthy subjects.
T-Cells recognizing MOG were detected in MS patients as well as in healthy subjects, and their precursor frequency in the blood was not increased in patients with MS.
MOG-reactive T-Cells isolated from both MS patients and healthy subjects exhibited a similar Cytokine profile, producing InterLeukins (IL-4, IL-10) and Tumour Necrosis Factor (TNF), but not Interferon-gamma (IFN-γ).
And, recognized predominantly the ExtraCellular (residues 1-60) and the Transmembrane/Cytoplasmic (residues 154-218) domains of MOG.
In contrast, Anti-MOG AntiBodies derived from MS patients displayed a skewed reactivity pattern, even though the occurrence and Titers of Serum Anti-MOG AntiBodies were only slightly elevated in MS patients.
MS-derived AutoAntiBodies were predominantly directed at the 1-60 region of MOG, while naturally occurring AntiMOG AntiBodies derived from healthy individuals reacted selectively to the 154-218 domain.
These differences were statistically significant.
The findings of this study are consistent with the presence of Anti-MOG AntiBodies within DeMyelinating Lesions of MS and their role in the induction of DeMyelinating pathology in animal models.
The study has important implications in the understanding of the AutoImmune processes in MS.
Expansion Of CD5 - B-Cells In Multiple Sclerosis Correlates With CD80 (B7-1) Expression
Sellebjerg F, Jensen J, Jensen CV, Wiik A
Scand J Immunol 2002 Jul;56(1):101-7
University of Copenhagen, Department of Neurology, Glostrup Hospital, Denmark
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, AntiMyelin 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 AntiMyelin 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 AntiMyelin AntiBody production.