Persistence and evolution of allergen-specific IgE repertoires during subcutaneous specific immunotherapy Mattias Levin, PhD, Jasmine J. King, BS, Jacob.

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Presentation transcript:

Persistence and evolution of allergen-specific IgE repertoires during subcutaneous specific immunotherapy Mattias Levin, PhD, Jasmine J. King, BS, Jacob Glanville, BA, Katherine J.L. Jackson, PhD, Timothy J. Looney, PhD, Ramona A. Hoh, PhD, Adriano Mari, MD, Morgan Andersson, MD, Lennart Greiff, MD, Andrew Z. Fire, PhD, Scott D. Boyd, MD, PhD, Mats Ohlin, PhD Journal of Allergy and Clinical Immunology Volume 137, Issue 5, Pages 1535-1544 (May 2016) DOI: 10.1016/j.jaci.2015.09.027 Copyright © 2015 The Authors Terms and Conditions

Fig 1 Timing of SIT and sample collection. Blood samples at the 2-month and 1-year time points were obtained approximately 1 week after the preceding SIT vaccine injection. Samples were not obtained from the nonvaccinated group at 2 months. Journal of Allergy and Clinical Immunology 2016 137, 1535-1544DOI: (10.1016/j.jaci.2015.09.027) Copyright © 2015 The Authors Terms and Conditions

Fig 2 Detection of sequences related to the isolated allergen-specific scFvs over the time course of SIT by using HTS of antibody heavy chain rearrangements. Solid boxes indicate time points at which such related sequences were also detected by using HTS in the blood (red) or nasal biopsy (blue) samples. Sequences only identified after selection of scFvs from antibody libraries but not by means of HTS are not shown. Journal of Allergy and Clinical Immunology 2016 137, 1535-1544DOI: (10.1016/j.jaci.2015.09.027) Copyright © 2015 The Authors Terms and Conditions

Fig 3 Analysis of isotype expression, tissue localization, and clonal persistence of B cells belonging to clonal lineages containing IgE-expressing members in patients undergoing SIT. A, Isotype expression by allergen-specific B-cell clones containing IgE members for which the allergen specificity was determined compared with clones from patients undergoing SIT in whom IgE specificity is not known. The clones of known allergen specificity are more likely to contain B cells expressing other IgA-switched antibodies. Significance was determined by using the Fisher exact test. Two-tailed P values: *P = .01 to .05, **P = .001 to .01, ***P = .0001 to .001, and ****P < .0001. Clones containing only IgE members are not shown on the graph, but the difference was not significant with a 2-tailed P value of .077. Numbers above bars indicate the total number of clusters representing the given category. B, Tissue and blood distribution of allergen-specific B-cell clones containing IgE-expressing members. Clones of known allergen specificity were detected in both nasal biopsy and blood samples more frequently than clones whose allergen specificity was not identified. Data from all time points were included in this analysis. Clones in the blood or biopsy categories are also counted in the blood and biopsy category. C, Persistent detection of B cell from known allergen-specific clones versus clones of unknown specificity during SIT. The clones with identified allergen specificity were more likely to be identified at more than 1 time point during the SIT course. D, Time points at which allergen-specific IgE clones were detected. Numbers on the x-axis indicate the time point in days. Journal of Allergy and Clinical Immunology 2016 137, 1535-1544DOI: (10.1016/j.jaci.2015.09.027) Copyright © 2015 The Authors Terms and Conditions

Fig 4 Antibody heavy chain somatic mutation trees describing putative clonal evolution relationships between members of allergen-specific B-cell clones. Clone sets related to scFvs IT5-rD13 (A), IT6-nD16 (B), IT6-rD128 (C), IT6-nD17 (D), and IT6-rD111 (E) are shown. IgE sequences identified as allergen specific in phage display experiments are represented by diamonds, whereas clone members identified by means of deep sequencing of nasal biopsy specimens are shown as rectangles and clone members identified by means of deep sequencing of PBMC specimens are displayed as circles. Colors indicate the time point at which sequences were identified: red, 0 months; blue, 2 months; and green, 1 year of SIT. Symbols indicate the isotype expressed by the clone member. Nodes with no internal symbol represent IgE clone members, nodes with triangles represent IgG1, and nodes with a circled dot represent IgA members. Additional examples of trees are shown in Fig E8. Journal of Allergy and Clinical Immunology 2016 137, 1535-1544DOI: (10.1016/j.jaci.2015.09.027) Copyright © 2015 The Authors Terms and Conditions