myelin-basic-protein and Virus-Diseases

Multiple sclerosis (MS) is a demyelinating disease of the central nervous system (CNS) afflicting approximately 250,000 individuals in the United States. This inflammatory disease has variable clinical manifestations, ranging from a relapsing-remitting course to a chronic progressive disease. Approximately one third of MS patients have chronic progressive disease often leading to severe impairment of mobility, paralysis, poor vision, and disturbances of bladder and bowel function. Although the etiology and pathogenesis remain unknown, accumulating evidence supports the hypothesis that exposure to an as-yet-unidentified infectious agent(s) triggers an aberrant immune response against self nervous tissue in genetically susceptible individuals. The tenfold higher concordance rate for MS in monozygotic twins compared to dizygotic twins, the increased incidence of MS in women compared to men (2:1), and the familial and racial occurrence of MS provide strong evidence that genetic factors influence susceptibility to MS. The major predisposing genes in MS are the human leukocyte antigen (HLA) class II molecules, DR15 and DQw6, molecularly defined as HLA-DRB1, 1501-DQA1 0102-DQB1 0602. In certain ethnic groups, MS susceptibility is more strongly associated with other DR molecules. Environmental factors are also believed to play a role, as suggested by the unique worldwide prevalence, migration effects, and epidemiological studies. Increased serum and cerebrospinal fluid antibody titers to numerous viruses have been reported; however, there have been no confirmed studies detecting viral RNA or antigen in MS brain tissue. At the present time, no known treatment can significantly alter the progression of MS. Based on the postulate that MS is an autoimmune disease associated with abnormalities in immunoregulation, a number of different immunosuppressive and immunomodulating agents have been tested as therapeutic modalities. In this article, we review the circumstantial evidence suggesting that immune system abnormalities are associated with the disease process, and provide an update on current therapies used in MS.

Topics: Animals; Antibodies, Monoclonal; Autoantigens; Autoimmune Diseases; Brain; Clinical Trials as Topic; Epitopes; Female; Gene Rearrangement, T-Lymphocyte; HLA-DR Antigens; Humans; Immunoglobulins, Intravenous; Immunosuppression Therapy; Immunosuppressive Agents; Immunotherapy; Lymphatic Irradiation; Lymphocyte Subsets; Male; Mice; Mice, SCID; Molecular Mimicry; Multiple Sclerosis; Myelin Basic Protein; Virus Diseases

Topics: Autoimmune Diseases; Humans; Multiple Sclerosis; Myelin Basic Protein; Slow Virus Diseases; Virus Diseases

A rapid method for similarity searches (FASTP program) was used to identify similarities between a protein database and the human basic proteins from myelin [P2 protein and 17.2K, 18.5K, and 21.5K variants of myelin basic protein (MBP)]. From similarity scores, we concluded that none of the presently known proteins are in a family containing the MBPs. No new members were found for the lipid-binding family of which P2 is a member. Sequence similarities deemed relevant to the molecular mimicry hypothesis for virus-induced autoimmunity were identified in FASTP data with the aid of microcomputer programs. Several MBP/viral protein similarities were found that have not been reported previously. Of note because of their association with demyelinating conditions were proteins from visna and vaccinia. Similarity with visna was specific to the 21.5K and 20.2K MBPs. The most interesting new possibility for mimicry involving the P2 protein was between the influenza A NS2 protein and a sequence region of P2 thought to be neuritogenic in animals and mitogenic for lymphocytes from some patients with Guillain-Barré syndrome (GBS). This may have relevance for some cases of GBS associated with the 1976 U.S.A. swine flu vaccination program. Because FASTP reports only the best similarities between proteins, searches with FASTP may not have detected all the examples of mimicry present in the database. Searches might also be more effective if similarities could be scored on immunological rather than structural relatedness.

Topics: Animals; Base Sequence; Biological Evolution; Humans; Information Systems; Myelin Basic Protein; Sequence Homology, Nucleic Acid; Software; Viral Proteins; Virus Diseases

Topics: Animals; Antibody Formation; Antigens; Autoimmune Diseases; Cell Migration Inhibition; Cyclophosphamide; Disease Models, Animal; Encephalomyelitis; Guinea Pigs; Haplorhini; Humans; Immunity, Cellular; Immunization; Immunoglobulin G; Lymphocyte Activation; Methotrexate; Multiple Sclerosis; Myelin Basic Protein; Nerve Tissue Proteins; Protein Binding; Rabbits; Rats; Skin Tests; Virus Diseases

Topics: Adult; Amino Acid Sequence; Base Sequence; Cloning, Molecular; Codon; Genetic Predisposition to Disease; Humans; Molecular Sequence Data; Myelin Basic Protein; Nucleic Acid Conformation; RNA, Messenger; Virus Diseases

Topics: Diagnosis, Differential; Epitopes; Humans; Immunoglobulin G; Multiple Sclerosis; Myelin Basic Protein; Myelin Proteins; Myelin Sheath; Nervous System; Oligodendroglia; Prognosis; Virus Diseases

Topics: Acetylcholine; Amyotrophic Lateral Sclerosis; Antigen-Antibody Complex; Autoantibodies; Cell Division; Cells; Humans; Kidney Glomerulus; Lymphocytic choriomeningitis virus; Myelin Basic Protein; Neurons; Time Factors; Virus Diseases

Topics: Antibodies; Autoimmune Diseases; Epitopes; Humans; Immunization; Lymphocytes; Measles; Measles virus; Multiple Sclerosis; Myelin Basic Protein; Time Factors; Virus Diseases