title: Epitope-specific immune tolerization ameliorates experimental autoimmune encephalomyelitis.
abstract: The availability of glatiramer acetate (GA) for inducing immune tolerance is a significant advancement in the treatment of multiple sclerosis (MS). However, a sizable proportion of patients maintain active disease, regardless of treatment. Another approach to induce T-cell tolerance is therefore still an unmet medical need. We hypothesized that induction of mucosal tolerance toward a pro-inflammatory T-cell epitope derived from a heat shock protein (HSP) (RatP2) could translate into clinical benefit. We found that treatment of experimental autoimmune encephalomyelitis (EAE, a model of MS) with the peptide RatP2 determined a significant clinical improvement, which was comparable to the standard tolerization treatment (an MBP-derived peptide pool) and superior to GA. Histological analysis demonstrated a reduction of brain and spinal cord inflammatory lesions in treated animals. Moreover, with immunological analysis we identified biomarkers associated with clinical response. This work provides proof-of-concept to support the further testing of this approach as a possible complement to currently available therapies for MS.
authors.affiliation: Kai BioEnergy, 3525-723 Del Mar Heights Road, San Diego, CA 92130, USA.
authors.forename: Rosario
authors.initials: R
authors.lastname: Billetta
authors.forename: Negar
authors.initials: N
authors.lastname: Ghahramani
authors.forename: Olivia
authors.initials: O
authors.lastname: Morrow
authors.forename: Berent
authors.initials: B
authors.lastname: Prakken
authors.forename: Huib
authors.initials: H
authors.lastname: de Jong
authors.forename: Carol
authors.initials: C
authors.lastname: Meschter
authors.forename: Paola
authors.initials: P
authors.lastname: Lanza
authors.forename: Salvatore
authors.initials: S
authors.lastname: Albani
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005260:Female; D000068717:Glatiramer Acetate; D006360:Heat-Shock Proteins / Q000737:chemistry / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance; D018928:Immunity, Mucosal; D008969:Molecular Sequence Data; D009103:Multiple Sclerosis / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000276:immunology / Q000494:pharmacology*; D010455:Peptides / Q000276:immunology / Q000494:pharmacology*; D051381:Rats; D011917:Rats, Inbred Lew; D013116:Spinal Cord / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism
chemical_list: D018984:Epitopes, T-Lymphocyte; D006360:Heat-Shock Proteins; D010446:Peptide Fragments; D010455:Peptides; D000068717:Glatiramer Acetate