P0 glycoprotein peptides 56-71 and 180-199 dose-dependently induce acute and chronic experimental autoimmune neuritis in Lewis rats associated with epitope spreading

Autor: Peter H. van der Meide, Sigliti-Henrietta Pelidou, Michael Levi, Jie Zhu, Eilhard Mix, Bengt Winblad, Georgia Deretzi, Li-Ping Zou
Rok vydání: 2001
Předmět:
Male
medicine.medical_specialty
Encephalomyelitis
Autoimmune
Experimental
Encephalomyelitis
Autoimmune
Experimental/chemically induced/*immunology
Immunology
Neuritis
Molecular Sequence Data
Dose-Response Relationship
Immunologic
Inflammation
In Vitro Techniques
Guillain-Barre Syndrome
Interferon-gamma
Immune system
Antigen
Internal medicine
Interferon-gamma/immunology/secretion
Immunology and Allergy
Medicine
Animals
Interferon gamma
Amino Acid Sequence
Myelin P0 Protein/chemistry/*immunology/*pharmacology
chemistry.chemical_classification
Immunodominant Epitopes/*immunology
B-Lymphocytes
Guillain-Barre syndrome
business.industry
Immunodominant Epitopes
B-Lymphocytes/immunology
Guillain-Barre Syndrome/immunology
medicine.disease
Peptide Fragments/immunology/pharmacology
Peptide Fragments
Rats
Mononuclear cell infiltration
Disease Models
Animal
Endocrinology
Neurology
chemistry
Rats
Inbred Lew
Acute Disease
Chronic Disease
Neurology (clinical)
medicine.symptom
business
Glycoprotein
Myelin P0 Protein
medicine.drug
Zdroj: Journal of neuroimmunology. 114(1-2)
ISSN: 0165-5728
Popis: Two synthetic peripheral nerve myelin P0 protein peptides, an immunodominant (amino acids 180-199) and a cryptic (amino acids 56-71) one, induced an acute or chronic course of experimental autoimmune neuritis (EAN) in Lewis rats, when given at low dose (50-100 microg/rat) or high dose (250 microg/rat), respectively. Corresponding to the different clinical course, pathological changes and immune responses were found: (1) Onset of clinical signs of P0 peptide 56-71 (P0 56-71) induced EAN was 1-3 days later than in P0 peptide 180-199 (P0 180-199) induced EAN at all immunizing doses, whereas the peak of the disease occurred at a similar time point post immunization (p.i.), i.e. at days 14-16 p.i. in P0 56-71 induced EAN and at day 16 p.i. in P0 180-199 induced EAN. (2) Intramolecular epitope spreading as assessed by delayed type hypersensitivity response occurred in P0 56-71 induced EAN at both low and high antigen doses and in P0 180-199 induced EAN at high antigen dose (250 microg/rat) only. (3) P0 180-199 stimulated higher levels of interferon-gamma production in P0 180-199 induced EAN than in P0 56-71 induced EAN and vice versa. (4) Histopathologic evaluation revealed a similar grade of mononuclear cell infiltration in the sciatic nerves of both types of EAN, but more severe demyelination was found in P0 180-199 induced EAN compared to P0 56-71 induced EAN. The results support the hypothesis that high dose autoantigen immunization induces extensive determinant spreading and chronic course of autoimmune diseases. J Neuroimmunol
Databáze: OpenAIRE
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