| Title: |
Epitope-specific neutralizing IgG4 antibodies are a biomarker of sustained tolerance for IgE mediated peanut allergy 9140 |
| Authors: |
Keswani, Tarun; LaHood, Nicole A.; Orlee Marini-Rapoport, Orlee; Zong, Guangning; Min, Jungki; Lytle, Isabelle R.; Bhowmik, Moumita; Pedersen, Lars; Mueller, Geoffrey A.; Patil, Sarita |
| Source: |
The Journal of Immunology ; volume 214, issue Supplement_1 ; ISSN 0022-1767 1550-6606 |
| Publisher Information: |
Oxford University Press (OUP) |
| Publication Year: |
2025 |
| Description: |
Description Sustained clinical tolerance to food allergens can be induced by oral immunotherapy (OIT). We previously identified neutralizing IgG4 antibodies (nAbs) as key players in disrupting allergen-IgE binding . Furthermore, using an inhibitory ELISA, we used a combination of two nAbs to identify that the induction of nAbs occurs during OIT only in those with sustained tolerance. Here, we seek to develop a quantitative assay to test the utility of nAbs as an early biomarker of allergic tolerance. We will compare nAbs using protein G purified plasma from OIT-treated peanut allergic patients with sustained and non-sustained tolerance. Using previously identified mAbs, we developed a flow cytometry bead-based assay (BBNA) using streptavidin coated beads and biotinylated mutated recombinant Arah2 (rArah2). Quantitative fluorescent flow cytometry beads were used for antibody quantitation. We validated the use of mrArah2 using biolayer interferometry and mAbs. The BBNA is highly sensitive and reproducible (CV-2.5%). The BBNA correlates with previously published ELISA (R2=0.9) data. The induction of IgG4 nAbs occurs only in sustained tolerance by BBNA (P < 0.01). A quantitative, sample-sparing BBNA assay assessing direct antibody binding to rArah2 reliably identifies serum nAbs in OIT-treated allergic patients. OIT-induced nAbs occurs only in sustained responses. Therefore, nAbs BBNA could be a valuable serum biomarker to predict long term clinical tolerance in peanut oral immunotherapy. Funding Sources NIAID, NIH (5R01AI155630, 1R21AI159732, to SUP); NIEHS, NIH (1ZIAES102906, to GAM; 1ZICES102645, to LCP); Food Allergy Science Initiative award (SUP). The clinical trial work at Harvard Clinical and Translational Science Center (1UL1TR001102 and 8UL1TR000170) from the National Center for Advancing Translational Science, and 1UL1 RR025758 from the National Center for Research Resources. Topic Categories Immune Mechanisms of Human Disease (HUM) |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| DOI: |
10.1093/jimmun/vkaf283.2582 |
| Availability: |
https://doi.org/10.1093/jimmun/vkaf283.2582; https://academic.oup.com/jimmunol/article-pdf/214/Supplement_1/vkaf283.2582/65412011/vkaf283.2582.pdf |
| Rights: |
https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model |
| Accession Number: |
edsbas.69C9310A |
| Database: |
BASE |