AIT mechanism |
Key findings |
References |
Dynamics of the immune response during HDM-SCIT using gene coexpression networks |
2-stage 'rewiring': early symptom reduction (during up-dosing) is associated with initial merging of Th2-effector and IL-2/T-regulatory network modules, without major quantitative changes in gene expression The 2nd phase (end of 2nd year) involves fusion with an upregulated type 1 interferon signaling module, potentially stabilizing Th2-antagonistic treatment effects |
Jones AC, Anderson D, Troy NM, et al. Rewiring of gene networks underlying mite allergen-induced CD4+ Th-cell responses during immunotherapy [published online ahead of print, 2020 Mar 17]. Allergy. 2020;10.1111/all.14265 |
T-follicular helper cells |
Specialized subset of CD4+ T cells that regulate B-cell responses within the germinal center Enhanced frequency and function in the tonsils of HDM-sensitized children making them specifically amenable to SLIT |
Foster WS, Grime CJ, Tan HL, et al. Enhanced frequency and function of follicular T cells in the tonsils of house dust mite-sensitized children. Allergy. 2020;75(5):1240–43 |
Functional evaluation of Tregs induced by peptide AIT |
Tregs induced by peptide AIT express GARP and SATB1 GARP expression is as an activation marker of parasitic infection induced Tregs that strongly suppress allergic inflammation, thus is a novel potential mechanistic pathway for AIT SATB1 is a genome organizer protein expressed in a lineage-specific manner in CD4+ T-cells. SATB1-dependent Treg-cell-specific superenhancers activation is crucial for Treg-cell lineage specification in the thymus During the early Th2-cell differentiation, IL-5 expression is repressed through direct binding of SATB1 to the IL-5 promoter. Thus, SATB1 modulation might expand the impact of AIT on eosinophilic inflammation of particular interest for AIT in asthma |
Sharif H, Singh I, Kouser L, et al. Immunologic mechanisms of a short-course of Lolium perenne peptide immunotherapy: a randomized, double-blind, placebo-controlled trial. J Allergy Clin Immunol. 2019;144(3):738–49 |
Inducible iTR35 cells |
iTR35 promote production of IL-10 from CD19+ B cells, Breg subsets and Tfr cells |
Sharif H, Singh I, Kouser L, et al. Immunologic mechanisms of a short-course of Lolium perenne peptide immunotherapy: a randomized, double-blind, placebo-controlled trial. J Allergy Clin Immunol 2019;144(3):738–49 |
Circulating memory-like Tfr cells induced by peptide AIT |
Circulating memory-like Tfr share properties of memory cells and persist for long periods Distinct from their lymph nodes counterpart they strongly suppress B and Tfh cells |
Sharif H, Singh I, Kouser L, et al. Immunologic mechanisms of a short-course of Lolium perenne peptide immunotherapy: a randomized, double-blind, placebo-controlled trial. J Allergy Clin Immunol 2019;144(3):738–49 |
The cellular and clonal origin of IgE-memory responses |
Following mucosal allergen exposure via SLIT, human IgE memory resides in allergen-specific IgG+ memory B cells. These cells rapidly switch isotype, expand into short-lived IgE+ plasmablasts, and serve as a potential target for therapeutic intervention |
Hoof I, Schulten V, Layhadi JA, et al. Allergen-specific IgG+ memory B cells are temporally linked to IgE memory responses. J Allergy Clin Immunol 2020;146(1):180–91 |
Formation and maintenance of T-memory cells |
Specific epigenetic drivers and pathways, highly context-dependent and varying with each subpopulation and location The epigenetic signature has the potential to be modified, which is relevant from a therapeutic perspective |
Mikami N, Kawakami R, Chen KY, Sugimoto A, Ohkura N, Sakaguchi S. Epigenetic conversion of conventional T cells into regulatory T cells by CD28 signal deprivation. Proc Natl Acad Sci USA 2020;117(22):12258–68 Hayward SL, Scharer CD, Cartwright EK, et al. Environmental cues regulate epigenetic reprogramming of airway-resident memory CD8+ T cells. Nat Immunol 2020;21(3):309–20 |
Evaluation of switched memory B cells following AIT |
Frequencies and absolute numbers of circulating memory B cells are increased in allergic rhinitis patients. CD23 expression on CD19+ CD20+ CD27+ IgD− switched memory B cells was significantly enhanced and positively correlated with antigen-specific IgE levels, symptom scores, and Tfh2/Tfr cell ratio in allergic rhinitis patients Tfh2 cells from allergic rhinitis patients had a greater capacity to induce CD23 expression on switched memory B cells via IL-4 CD23 expression on switched memory B cells was downregulated after 12-month AIT, which positively associated with disease remission in allergic rhinitis patients |
Yao Y, Wang N, Chen CL, et al. CD23 expression on switched memory B cells bridges T-B-cell interaction in allergic rhinitis [published online ahead of print, 2020 Mar 21]. Allergy 2020;10.1111/all.14288 |
New simpler methods for measuring allergen-specific inhibitory antibody (IgG4) activity |
The IgE-FAB utilizes flow cytometry to measure the binding of allergen-IgE complexes to EBV-transformed B cells The ELI-FAB assay uses standard ELISA-based techniques to measure allergen-IgE binding to plate-bound CD23, the low-affinity IgE receptor expressed on B cells |
Shamji MH, Francis JN. Measurement of allergen-specific inhibitory antibody activity. Methods Mol Biol 2019;2020:33–43 |
AIT biomarkers |
Nasal IgG4-associated inhibitory activity correlates closely with the clinical response to SCIT in patients with allergic rhinitis with or without asthma |
Shamji MH, Kappen J, Abubakar-Waziri H, et al. Nasal allergen-neutralizing IgG4 antibodies block IgE-mediated responses: novel biomarker of subcutaneous grass pollen immunotherapy. J Allergy Clin Immunol. 2019;143(3):1067–76 |
|
IgD producing B cells expansion following HDM-SCIT for asthma correlated with the ability to control asthma |
Boonpiyathad T, Pradubpongsa P, Mitthamsiri W, Satitsuksanoa P, Jacquet A, Sangasapaviliya A. Allergen-specific immunotherapy boosts allergen-specific IgD production in house dust mite-sensitized asthmatic patients. Allergy 2020;75(6):1457–60 |
Comments