Journal of neuroimmunology
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Myasthenia gravis (MG), a prototypic antibody-mediated autoimmune disease, presents an excellent target for scientific research aimed at a better understanding of the disease itself and the source that triggers an autoimmune reaction in an organism. MG is a neuromuscular disease caused mainly by an autoimmune response against the nicotinic acetylcholine receptor (AChR) which interferes with neuromuscular transmission. ⋯ This review is dedicated to the late Prof. John Newsom-Davis, who was the first to introduce the use of plasmapheresis for MG.
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Two or more oligoclonal IgG bands (OB) detected by separation of cerebrospinal fluid (CSF) proteins while not demonstrable in corresponding serum reflect a local B-cell response accompanying central nervous system (CNS) inflammation. Using optimized, standardized methodology, preferentially protein separation by isoelectric focusing followed by immunoblotting, more than 95% of patients with multiple sclerosis (MS) have CSF OB of IgG class not detectable in serum, thereby providing powerful evidence for the diagnosis of MS. Once present, CSF OB persists in the individual patient irrespective of MS course or therapy. ⋯ There is a need for concerted long-term follow-up studies of the subgroup of MS patients without CSF OB regarding e.g. prognostic and immunologic features. For inclusion in trials of disease-modulating drugs, it is recommended that patients with MS or CIS are selected regarding presence vs. absence of CSF OB. Development and evaluation of new technologies to define local vs. systemic B-cell responses in patients with MS or CIS vs. patients with other inflammatory neurological diseases should shed new light on the role of CSF OB, which remains enigmatic.
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Multiple sclerosis (MS), the most important human inflammatory demyelinating disease of the central nervous system, is characterized by various clinical disease courses, inhomogeneous and unpredictable therapeutic effects, heterogenous genetic backgrounds and immunopathogenetic subtypes as demonstrated by neuropathology. Because of this heterogeneity of MS, a subtyping of our patients by genetical, clinical, neuroradiological, and neuroimmunological parameters will be necessary in the future. Therefore the importance of identifying biological markers for MS has evolved over the past years. ⋯ In this review we will give an overview on the current status and potential applicability of antibodies as biological markers for the diagnosis, classification, disease activity and prediction of clinical courses in MS. We will therefore summarize the findings on autoantibodies to myelin and nonmyelin antigens and on viral antigens in MS. We believe that antibodies serving as biomarkers will help to establish a differential therapeutic concept in MS, which will allow to treat individuals selectively according to their pathogenetic subtype and disease status.
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Cytokines, peptide hormones and neurotransmitters, as well as their receptors/ligands, are endogenous to the brain, endocrine and immune systems. These shared ligands and receptors are used as a common chemical language for communication within and between the immune and neuroendocrine systems. Such communication suggests an immunoregulatory role for the brain and a sensory function for the immune system. ⋯ Cytokines are chemical messengers that stimulate the HPA axis when the body is under stress or experiencing an infection. This review discusses current knowledge of cytokine signaling pathways in neuro-immune-endocrine interactions as viewed through the triplet HPA axis. In addition, we elaborate on HPA/cytokine interactions in oxidative stress within the context of nuclear factor-kappaB transcriptional regulation and the role of oxidative markers and related gaseous transmitters.
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Review Historical Article
The pathology of multiple sclerosis: a historical perspective.
In the century and a half since multiple sclerosis (MS) was first recognized, the pathology of the condition has been defined with increasing detail. From the recognition and definition of MS as a clinical phenomenon, studies of the diseased brain tissue have progressed in a manner dependent on the science of the time. ⋯ During this evolution, many hypotheses concerning the pathogenesis of MS have been overturned, and the interpretation of some clearly delineated gross and histological findings have been reversed. This review plots the progress and highlights current theories and emerging concepts regarding one of the most enigmatic of neurological diseases.