Modulation of T-cell response to phospholipase A2 and phospholipase A2–derived peptides by conventional bee venom immunotherapy  Regine Kämmerer, MDa,b,

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Presentation transcript:

Modulation of T-cell response to phospholipase A2 and phospholipase A2–derived peptides by conventional bee venom immunotherapy  Regine Kämmerer, MDa,b, Yolande Chvatchko, PhDa,b, Alexander Kettnera,b, Nathalie Dufoura, Giampietro Corradin, PhDb, François Spertini, MDa  Journal of Allergy and Clinical Immunology  Volume 100, Issue 1, Pages 96-103 (July 1997) DOI: 10.1016/S0091-6749(97)70200-8 Copyright © 1997 Mosby, Inc. Terms and Conditions

Fig. 1 CD8−PBMC response to PLA2 and its three LPs (1 to 60, 51 to 99, and 90 to 134) mapping whole PLA2 (10 μg/ml each or as a mixture of three LPs) at initiation of VIT (DO) and 14 weeks later (W14). Results are expressed as individual stimulation indices (open circles) and as the median (black cross). Statistical analysis was performed with the paired Wilcoxon signed-rank test. Responses to the TT control showed no significant variation during this time period. NS, Not significant; *, p < 0.05; **, p < 0.01. Journal of Allergy and Clinical Immunology 1997 100, 96-103DOI: (10.1016/S0091-6749(97)70200-8) Copyright © 1997 Mosby, Inc. Terms and Conditions

Fig. 2 CD8−PBMC proliferation in response to peptides 51 to 99 and 90 to 134 at initiation of VIT (DO), at week 3 (W3), at week 6 (W6), and at the end of the incremental dose period (W14). Results show the distribution of stimulation indices from individual subjects as boxes (percentile 25, lower border; median, bold line; percentile 75, upper border) and whiskers (percentile 10, lower whisker; percentile 90, upper whisker). Statistical analysis between stimulation indices for each peptide at indicated time points was done with KruskaI-Wallis nonparametric analysis of variance tests (p < 0.01). Journal of Allergy and Clinical Immunology 1997 100, 96-103DOI: (10.1016/S0091-6749(97)70200-8) Copyright © 1997 Mosby, Inc. Terms and Conditions

Fig. 3 CD8−PBMC responses from group I and group II patients to PLA2 and its three LPs. Results are expressed as the distribution of individual data (stimulation indices) as described in Fig. 2. Statistical analysis between results from group I and II was done with the unpaired Wilcoxon signed-rank test. Responses to TT control showed no significant variation between groups. NS, Not significant; *, p < 0.05; ***, p < 0.001. Journal of Allergy and Clinical Immunology 1997 100, 96-103DOI: (10.1016/S0091-6749(97)70200-8) Copyright © 1997 Mosby, Inc. Terms and Conditions

Fig. 4 Serum levels (in kU/L) of specific IgE against whole BV (A and C) and PLA2 (B and D) in group I patients (A and B) at initiation of VIT (DO) and 14 weeks later (W14), and in group II patients (C and D) at initiation of VIT and after 3 to 5 years of VIT. L. Statistical analysis was done with a paired Student's t test NS; Not significant, *, p < 0.05; **, p < 0.01). Journal of Allergy and Clinical Immunology 1997 100, 96-103DOI: (10.1016/S0091-6749(97)70200-8) Copyright © 1997 Mosby, Inc. Terms and Conditions

Fig. 4 Serum levels (in kU/L) of specific IgE against whole BV (A and C) and PLA2 (B and D) in group I patients (A and B) at initiation of VIT (DO) and 14 weeks later (W14), and in group II patients (C and D) at initiation of VIT and after 3 to 5 years of VIT. L. Statistical analysis was done with a paired Student's t test NS; Not significant, *, p < 0.05; **, p < 0.01). Journal of Allergy and Clinical Immunology 1997 100, 96-103DOI: (10.1016/S0091-6749(97)70200-8) Copyright © 1997 Mosby, Inc. Terms and Conditions

Fig. 4 Serum levels (in kU/L) of specific IgE against whole BV (A and C) and PLA2 (B and D) in group I patients (A and B) at initiation of VIT (DO) and 14 weeks later (W14), and in group II patients (C and D) at initiation of VIT and after 3 to 5 years of VIT. L. Statistical analysis was done with a paired Student's t test NS; Not significant, *, p < 0.05; **, p < 0.01). Journal of Allergy and Clinical Immunology 1997 100, 96-103DOI: (10.1016/S0091-6749(97)70200-8) Copyright © 1997 Mosby, Inc. Terms and Conditions

Fig. 4 Serum levels (in kU/L) of specific IgE against whole BV (A and C) and PLA2 (B and D) in group I patients (A and B) at initiation of VIT (DO) and 14 weeks later (W14), and in group II patients (C and D) at initiation of VIT and after 3 to 5 years of VIT. L. Statistical analysis was done with a paired Student's t test NS; Not significant, *, p < 0.05; **, p < 0.01). Journal of Allergy and Clinical Immunology 1997 100, 96-103DOI: (10.1016/S0091-6749(97)70200-8) Copyright © 1997 Mosby, Inc. Terms and Conditions

Fig. 5 Serum levels of specific IgG (A and C) and IgG4 (B and D) against whole BV in group I patients (A and B) at initiation of VIT (DO) and 14 weeks later (W14) and in group II patients (C and D) at initiation of VIT and after 3 to 5 years of VIT. Results are reported as percentage of a reference serum sample. Statistical analysis was done with a paired Student's t test NS; not significant; *, p  < 0.05. Journal of Allergy and Clinical Immunology 1997 100, 96-103DOI: (10.1016/S0091-6749(97)70200-8) Copyright © 1997 Mosby, Inc. Terms and Conditions

Fig. 5 Serum levels of specific IgG (A and C) and IgG4 (B and D) against whole BV in group I patients (A and B) at initiation of VIT (DO) and 14 weeks later (W14) and in group II patients (C and D) at initiation of VIT and after 3 to 5 years of VIT. Results are reported as percentage of a reference serum sample. Statistical analysis was done with a paired Student's t test NS; not significant; *, p  < 0.05. Journal of Allergy and Clinical Immunology 1997 100, 96-103DOI: (10.1016/S0091-6749(97)70200-8) Copyright © 1997 Mosby, Inc. Terms and Conditions

Fig. 5 Serum levels of specific IgG (A and C) and IgG4 (B and D) against whole BV in group I patients (A and B) at initiation of VIT (DO) and 14 weeks later (W14) and in group II patients (C and D) at initiation of VIT and after 3 to 5 years of VIT. Results are reported as percentage of a reference serum sample. Statistical analysis was done with a paired Student's t test NS; not significant; *, p  < 0.05. Journal of Allergy and Clinical Immunology 1997 100, 96-103DOI: (10.1016/S0091-6749(97)70200-8) Copyright © 1997 Mosby, Inc. Terms and Conditions

Fig. 5 Serum levels of specific IgG (A and C) and IgG4 (B and D) against whole BV in group I patients (A and B) at initiation of VIT (DO) and 14 weeks later (W14) and in group II patients (C and D) at initiation of VIT and after 3 to 5 years of VIT. Results are reported as percentage of a reference serum sample. Statistical analysis was done with a paired Student's t test NS; not significant; *, p  < 0.05. Journal of Allergy and Clinical Immunology 1997 100, 96-103DOI: (10.1016/S0091-6749(97)70200-8) Copyright © 1997 Mosby, Inc. Terms and Conditions

Fig. 6 Cytokine secretion by short-term T cell lines from patients hypersensitive to BV, which were stimulated with PMA/ionomycin for 24 hours: lines were raised against a mixture of three LPs mapping PLA2, at initiation of VIT (DO), after 14 weeks of VIT (W14) (group I patients), and at the end of VIT (>3 years) (group II patients). Solid bars indicate the median of cytokine secretion or cytokine ratio from five individual lines. Statistical analysis was done with a nonparametric analysis of variance test * p < 0.05, DO vs > 3 years). Journal of Allergy and Clinical Immunology 1997 100, 96-103DOI: (10.1016/S0091-6749(97)70200-8) Copyright © 1997 Mosby, Inc. Terms and Conditions

Fig. 6 Cytokine secretion by short-term T cell lines from patients hypersensitive to BV, which were stimulated with PMA/ionomycin for 24 hours: lines were raised against a mixture of three LPs mapping PLA2, at initiation of VIT (DO), after 14 weeks of VIT (W14) (group I patients), and at the end of VIT (>3 years) (group II patients). Solid bars indicate the median of cytokine secretion or cytokine ratio from five individual lines. Statistical analysis was done with a nonparametric analysis of variance test * p < 0.05, DO vs > 3 years). Journal of Allergy and Clinical Immunology 1997 100, 96-103DOI: (10.1016/S0091-6749(97)70200-8) Copyright © 1997 Mosby, Inc. Terms and Conditions

Fig. 6 Cytokine secretion by short-term T cell lines from patients hypersensitive to BV, which were stimulated with PMA/ionomycin for 24 hours: lines were raised against a mixture of three LPs mapping PLA2, at initiation of VIT (DO), after 14 weeks of VIT (W14) (group I patients), and at the end of VIT (>3 years) (group II patients). Solid bars indicate the median of cytokine secretion or cytokine ratio from five individual lines. Statistical analysis was done with a nonparametric analysis of variance test * p < 0.05, DO vs > 3 years). Journal of Allergy and Clinical Immunology 1997 100, 96-103DOI: (10.1016/S0091-6749(97)70200-8) Copyright © 1997 Mosby, Inc. Terms and Conditions