Oligoclonal immunoglobulins and plasma cells in spinal fluid of patients with multiple sclerosis.

Thompson, Edward J.; Kaufmann, Peter; Shortman, R. C.; Rudge, Peter; McDonald, W. I.

doi:10.1136/bmj.1.6155.16

Cited by 80 publications

(16 citation statements)

References 14 publications

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“…Cerebrospinal fluids from 90% of MS patients display a restricted heterogeneous distribution after electrophoresis, giving rise to oligoclonal bands [51]. Although other neurological disorders are associated with oligoclonal bands, the specificity of the antibodies in these bands is generally directed against the agent that causes the disease [6,52].…”

Section: Detection Of Antibodies In Csfmentioning

confidence: 99%

Multiple sclerosis is linked to Epstein‐Barr virus infection

Haahr

Höllsberg

2006

Reviews in Medical Virology

111

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The aetiology and pathogenesis of MS are unknown, but environmental agents, genetic susceptibility and stochastic events are likely to be involved. In order to evaluate the possibility that MS is linked to EBV infection, we here evaluate studies on MS- and EBV-epidemiology, prospective and retrospective analysis of EBV-serology, investigations of EBV DNA sequences in blood and tissues, specificity of antibodies in oligoclonal bands in MS patients and results from antiviral chemotherapy of MS patients. It could be demonstrated that EBV is complying with the epidemiological observations in MS and that all MS patients are seropositive to EBV in contrast to healthy controls. Importantly, despite difficulties in diagnosing child-MS, the vast majority of these patients are also EBV seropositive. In contrast to control groups, recent EBV infections have never been observed in children or adults with MS. Further prospective studies indicate a 2.8 times higher tendency for development of MS after infectious mononucleosis. In MS patients, unbiased analyses pull out EBV antigens as high-affinity targets for the antibodies in the oligoclonal bands. Humans are the exclusive natural host for EBV, a finding that may explain why MS is unique to humans. Together these unique observations strongly suggest a linkage between MS and EBV infection. Infection by EBV offers numerable mechanisms to perturb the immune system, including mimicry and superantigen induction, which may potentially participate in the disease mechanisms. In contrast, studies demonstrating higher IgG titres and occurrence of viral DNA in serum/plasma are likely to reflect a consequence of the disease. An explanation for a potential role of respiratory diseases in MS is discussed. It is concluded that the ultimate test to the hypothesis of MS and EBV is the development and application of an EBV vaccine, which is predicted to eradicate the disease.

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Section: Detection Of Antibodies In Csfmentioning

confidence: 99%

Multiple sclerosis is linked to Epstein‐Barr virus infection

Haahr

Höllsberg

2006

Reviews in Medical Virology

111

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“…Although oligoclonal IgG is often found in the cerebrospinal fluid (CSF) of individuals with MS (ref. 9), the specificities of these locally produced antibodies and their role in disease progression are not known. A substantial fraction of individuals with neuromyelitis optica, a variant of MS in which the optic nerves and spinal cord are primarily affected, were recently shown to have autoantibodies against the aquaporin-4 water channel localized on astrocyte foot processes at the blood-brain barrier 10 .…”

Section: Introductionmentioning

confidence: 99%

Self-antigen tetramers discriminate between myelin autoantibodies to native or denatured protein

O’Connor

McLaughlin

Jager

et al. 2007

Nat Med

361

302

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The role of autoantibodies in the pathogenesis of multiple sclerosis (MS) and other demyelinating diseases is controversial, in part because widely used western blotting and ELISA methods either do not permit the detection of conformation-sensitive antibodies or do not distinguish them from conformation-independent antibodies. We developed a sensitive assay based on self-assembling radiolabeled tetramers that allows discrimination of antibodies against folded or denatured myelin oligodendrocyte glycoprotein (MOG) by selective unfolding of the antigen domain. The tetramer radioimmunoassay (RIA) was more sensitive for MOG autoantibody detection than other methodologies, including monomer-based RIA, ELISA or fluorescent-activated cell sorting (FACS). Autoantibodies from individuals with acute disseminated encephalomyelitis (ADEM) selectively bound the folded MOG tetramer, whereas sera from mice with experimental autoimmune encephalomyelitis induced with MOG peptide immunoprecipitated only the unfolded tetramer. MOG-specific autoantibodies were identified in a subset of ADEM but only rarely in adult-onset MS cases, indicating that MOG is a more prominent target antigen in ADEM than MS.The role of autoantibodies in the pathogenesis of human demyelinating diseases of the central nervous system (CNS) is an important, unresolved issue. In animal models, autoantibodies that recognize epitopes on the surface of myelin or myelin-producing oligodendrocytes can enhance demyelination 1,2 . A monoclonal antibody (8-18C5) against myelin oligodendrocyte glycoprotein (MOG) induces severe demyelination in mice and rats with mild experimental autoimmune encephalomyelitis (EAE) but does not induce disease in healthy animals because the antibody cannot gain access to the CNS parenchyma 1,2 . MOG is a minor component of myelin but is localized on the outer surface of the multilamellar myelin structure and is thus accessible to antibodies, whereas more abundant antigens such as myelin basic protein are inaccessible in intact myelin 1 . In the marmoset primate model of EAE, immunization with MOG induces a chronic demyelinating disease with pathological features reminiscent of MS (ref. 3). In mouse models, however, severe demyelination is observed in the absence of antibodies and B cells 4 , indicating that autoantibodies are not required for demyelination in all species.These elegant studies in animal models have shown the demyelinating potential of autoantibodies to myelin surface proteins, but their role in the pathogenesis of human inflammatory demyelinating diseases such as MS and acute disseminated encephalomyelitis (ADEM) is far less certain. MOG has been extensively studied as a potential target antigen for autoantibodies in MS (refs. 5-8) Unlike MS, ADEM typically has a rapidly progressive clinical presentation that includes encephalopathy 11 . The disease course is usually self limiting, although in a minority of cases relapses may occur. The pathogenic relationship between MS and ADEM is unclear, and it remains to be d...

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“…10,11,26 Plasma cells have been observed in the CSF of 18-97% of MS patients. 1,6,11,[26][27][28] The explanation for such a wide variance must lie mostly in the different morphologic criteria used. We were able to find lymphoplasmacytes and/or mature plasma cells in 71.4% of MS patients.…”

Section: Qualitative Cytologymentioning

confidence: 99%