Allergen-specific T-cell tolerance induction with allergen-derived long synthetic peptides: Results of a phase I trial Jean-Marc Fellrath, MDa, Alexander.

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Presentation transcript:

Allergen-specific T-cell tolerance induction with allergen-derived long synthetic peptides: Results of a phase I trial Jean-Marc Fellrath, MDa, Alexander Kettner, PhDab, Nathalie Dufour, a, Christian Frigerio, MDa, Dominique Schneeberger, MDa, Annette Leimgruber, MDa, Gampietro Corradin, PhDb, François Spertini, MDa Journal of Allergy and Clinical Immunology Volume 111, Issue 4, Pages 854-861 (April 2003) DOI: 10.1067/mai.2003.1337 Copyright © 2003 Mosby, Inc. Terms and Conditions

Fig. 1 PLA2-derived long synthetic peptide therapy induces specific T-cell anergy in patients hypersensitive to BV. Hatched columns, Peptide group; open columns, control group (treated with albumin). Results are expressed as ratio of stimulation indexes in response to the mixture of the three LSPs reported to the stimulation indexes obtained in response to PMA (100 ng/mL)/Ionomycine (1 μmol/L) used as interassay standard. Results are presented as box-and-whisker plots with successive percentiles 5, 25, 50, 75, and 95. Medians are indicated by thick bars . Difference within groups was examined by a Friedmann nonparametric ANOVA test (peptide group, P = .035; control group, P = .95), completed by a multicomparison Dunn test (peptide group: day 0 vs day 14, P < .001; day 14 vs day 80, P < .05). Journal of Allergy and Clinical Immunology 2003 111, 854-861DOI: (10.1067/mai.2003.1337) Copyright © 2003 Mosby, Inc. Terms and Conditions

Fig. 2 Long synthetic peptide therapy deviates T-cell cytokine response and strongly stimulates IL-10 secretion. Cytokines (A, IL-4; B, IFN-γ; C, IL-10) from supernatants of short-term T-cell lines were measured by ELISA in cell supernatant. Results are presented as box-and-whisker plots with successive percentiles 5, 25, 50, 75, and 95. Medians are indicated by thick bars . Difference within groups for each cytokine was examined by Kruskal-Wallis nonparametric ANOVA test (P > .05 for IL-4, P = .018 for IFN-γ, P = .012 for IL-10), completed by a Mann-Whitney nonparametric test as mentioned in the figure (B, IFN-γ, day 0 vs day 42, P < .05; C, IL-10, day 0 vs day 42, P < .02). Journal of Allergy and Clinical Immunology 2003 111, 854-861DOI: (10.1067/mai.2003.1337) Copyright © 2003 Mosby, Inc. Terms and Conditions

Fig. 3 Anti-PLA2-specific serum IgE and IgG4. Anti-PLA2-specific serum IgE (A and B ) and IgG4 (C and D ) were measured in the peptide group (A and C ) and the control group (B and D ) at indicated time points. Median values are indicated by thick bars . Each point represents an individual value. Difference within groups was examined by Friedman nonparametric ANOVA test, completed in C by multicomparison posttest (P < .01, P < .05, and P < .05 for day 0 vs days 42, 70, and 80, respectively). Journal of Allergy and Clinical Immunology 2003 111, 854-861DOI: (10.1067/mai.2003.1337) Copyright © 2003 Mosby, Inc. Terms and Conditions

Fig. 4 Intradermal skin tests with peptides and native PLA2. Results are expressed as end point concentrations (log10 scale) at enrollment into the study (day 0) and after the last injection at day 70 in patients from the peptide group (A and B ) and the control group (C and D ), tested, respectively, with the three long synthetic peptides (as a mixture) (A and C ) and with native PLA2 (B and D ). Journal of Allergy and Clinical Immunology 2003 111, 854-861DOI: (10.1067/mai.2003.1337) Copyright © 2003 Mosby, Inc. Terms and Conditions

Fig. 5 In vitro IgE binding to whole BV and native PLA2 (A and B ) and to long synthetic peptides LSP1-60, LSP47-99, and LSP90-134 (C, D, and E, respectively) was analyzed by dot blot assays after each injection. Results are expressed as absorbance arbitrary units. Open columns, Control group; hatched columns, peptide group. Journal of Allergy and Clinical Immunology 2003 111, 854-861DOI: (10.1067/mai.2003.1337) Copyright © 2003 Mosby, Inc. Terms and Conditions