myelin-basic-protein and Drug-Hypersensitivity

In this 'double-blind', randomized, placebo-controlled phase II trial, we compared an altered peptide ligand of myelin basic protein with placebo, evaluating their safety and influence on magnetic resonance imaging in relapsing-remitting multiple sclerosis. A safety board suspended the trial because of hypersensitivity reactions in 9% of the patients. There were no increases in either clinical relapses or in new enhancing lesions in any patient, even those with hypersensitivity reactions. Secondary analysis of those patients completing the study showed that the volume and number of enhancing lesions were reduced at a dose of 5 mg. There was also a regulatory type 2 T helper-cell response to altered peptide ligand that cross-reacted with the native peptide.

Topics: Dose-Response Relationship, Drug; Drug Hypersensitivity; Humans; Incidence; Ligands; Magnetic Resonance Imaging; Multiple Sclerosis; Myelin Basic Protein; Peptide Fragments; Peptides; Th2 Cells

In strain-13 guinea-pigs inoculated for chronic relapsing experimental allergic encephalomyelitis (CR-EAE), IgG1 and IgG2 subclass antibody responses were investigated using single radial immunodiffusion and enzyme-linked immunosorbent assays (ELISA) for IgG1 and IgG2 specific for whole cord, myelin, myelin basic protein and Mycobacterium tuberculosis. The early acute stage revealed no increase in IgG1 but was associated with increased levels of IgG2 specific for neural and adjuvant components. Throughout the chronic phase of the disease, there were increased levels of IgG of both subclasses specific for the antigens tested but a preferential synthesis of IgG1. Levels of both IgG1 and IgG2 specific for neuroantigens were lowest in those guinea-pigs which did not develop signs of chronic disease. Immediate skin sensitivity against a wide range of neural antigens was not demonstrated though positive results may have been masked by the ability of myelin basic protein to induce non-specific mast cell degranulation and by altered histamine responsiveness in disease. Guinea-pigs with chronic paralysis had a lower skin sensitivity to histamine, compound 48/80 and M. tuberculosis than those in remission.

Topics: Animals; Antibodies, Bacterial; Autoantibodies; Drug Hypersensitivity; Encephalomyelitis, Autoimmune, Experimental; Enzyme-Linked Immunosorbent Assay; Guinea Pigs; Hypersensitivity, Immediate; Immunodiffusion; Immunoglobulin G; Intradermal Tests; Mycobacterium tuberculosis; Myelin Basic Protein; Myelin Sheath; Spinal Cord

In the present report we provide the strain distribution patterns of susceptibility to acute mouse hepatitis virus type-4 (MHV-4) encephalomyelitis, acute experimental allergic encephalomyelitis (EAE) and vasoactive amine sensitivity (VAAS) for 9 (CXJ) recombinant-inbred strains between BALB/cKe (C) and SJL/J(J) mice. We confirm that susceptibility to MHV-4 is not linked to the H-2 complex, and that all strains susceptible to acute EAE have both a responder H-2 haplotype (H-2s or H-2d) and induced (B. pertussis) VAAS. In addition, we provide evidence that susceptibility to acute EAE induction is controlled by an additional presently unmapped locus and that an EAE-like histopathological disease does not usually follow MHV-4 infection intracerebrally in animals susceptible to MHV-4, acute EAE and induced VAAS.

Topics: Animals; Bordetella pertussis; Drug Hypersensitivity; Encephalomyelitis; Encephalomyelitis, Autoimmune, Experimental; Female; H-2 Antigens; Haploidy; Hepatitis, Viral, Animal; Histamine; Humans; Immunity, Innate; Male; Mice; Mice, Inbred Strains; Murine hepatitis virus; Myelin Basic Protein; Rats