title: Persistence of immune responses to altered and native myelin antigens in patients with multiple sclerosis treated with altered peptide ligand.
abstract: Altered peptide ligands (APLs) can modulate responses of T cells to native peptide antigens implicated in the pathogenesis of autoimmune diseases. An APL of the putative target antigen myelin basic protein (MBP) peptide 83-99 has been used in abbreviated clinical trials in patients with multiple sclerosis (MS). Our objective was to assess the long-term persistence, and characteristics, of the APL-induced immune response in such patients. We measured the ex vivo proliferative frequency to the APL and native MBP, the cross-reactivity, and the cytokine production by these lines. We found that a 4- to 16-week course of APL therapy could induce a persistent (2-4.5 year) increase in the frequency of T cells responsive to both the APL and the native MBP in a select number of patients. These T cells produced high levels of IL-5, contrasting with the pretreatment observation that the responses to either antigen were IFNgamma (Th1) dominant. Our results indicate that APL therapy can induce persistent Th2-directed immune deviation. Understanding the impact of such APL-induced immune responses on MS disease activity will require additional clinical trials that incorporate careful monitoring of both clinical and immunological parameters.
authors.affiliation: Neuroimmunology Unit, Department of Neurology, Montreal Neurological Institute, McGill University, Montreal, Canada.
authors.forename: H J
authors.initials: HJ
authors.lastname: Kim
authors.forename: J P
authors.initials: JP
authors.lastname: Antel
authors.forename: P
authors.initials: P
authors.lastname: Duquette
authors.forename: D G
authors.initials: DG
authors.lastname: Alleva
authors.forename: P J
authors.initials: PJ
authors.lastname: Conlon
authors.forename: A
authors.initials: A
authors.lastname: Bar-Or
mesh_terms: D000328:Adult; D015331:Cohort Studies; D003429:Cross Reactions; D006801:Humans; D007111:Immunity, Cellular; D016898:Interferon-alpha / Q000032:analysis; D015848:Interleukin-5 / Q000032:analysis; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000276:immunology; D004676:Myelin Basic Protein / Q000627:therapeutic use*; D010446:Peptide Fragments / Q000627:therapeutic use*; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology
chemical_list: D016898:Interferon-alpha; D015848:Interleukin-5; D004676:Myelin Basic Protein; D010446:Peptide Fragments; C104448:myelin basic protein 83-99