TY - JOUR
T1 - Acute FPIES reactions are associated with an IL-17 inflammatory signature
AU - Berin, M. Cecilia
AU - Lozano-Ojalvo, Daniel
AU - Agashe, Charuta
AU - Baker, Mary Grace
AU - Bird, J. Andrew
AU - Nowak-Wegrzyn, Anna
N1 - Funding Information:
Funded in part by the Katy and Kyle Miller Family Fund , the National Institutes of Health (grants AI136053 and AI151707 ), the Louis and Rachel Rudin Foundation (to M.G.B.), and the National Institutes of Health–National Institute of Allergy and Infectious Diseases (to J.A.B.). A. Nowak-Wegrzyn received research support from the National Institute of Allergy and Infectious Diseases .
Funding Information:
Funded in part by the Katy and Kyle Miller Family Fund, the National Institutes of Health (grants AI136053 and AI151707), the Louis and Rachel Rudin Foundation (to M.G.B.), and the National Institutes of Health?National Institute of Allergy and Infectious Diseases (to J.A.B.). A. Nowak-Wegrzyn received research support from the National Institute of Allergy and Infectious Diseases.
Publisher Copyright:
© 2021 American Academy of Allergy, Asthma & Immunology
PY - 2021/9
Y1 - 2021/9
N2 - Background: Food protein–induced enterocolitis syndrome (FPIES) is a non–IgE-mediated food allergy characterized by profuse vomiting within hours of ingestion of the causative food. We have previously reported that FPIES is associated with systemic innate immune activation in the absence of a detectable antigen-specific antibody or T-cell response. The mechanism of specific food recognition by the immune system remains unclear. Objective: Our aim was to identify immune mechanisms underlying FPIES reactions by proteomic and flow cytometric analysis of peripheral blood. Methods: Children with a history of FPIES underwent supervised oral food challenge. Blood samples were taken at baseline, at symptom onset, and 4 hours after symptom onset. We analyzed samples from 23 children (11 reactors and 12 outgrown). A total of 184 protein markers were analyzed by proximity ligation assay and verified by multiplex immunoassay. Analysis of cell subset activation was performed by mass cytometry and spectral cytometry. Results: Symptomatic FPIES challenge results were associated with significant elevation of levels of cytokines and chemokines, including IL-17 family markers (IL-17A, IL-22, IL-17C, and CCL20) and T-cell activation (IL-2), and innate inflammatory markers (IL-8, oncostatin M, leukemia inhibitory factor, TNF-α, IL-10, and IL-6). The level of the mucosal damage marker regenerating family member 1 alpha (REG1A) was also significantly increased. These biomarkers were not increased in asymptomatic challenges or IgE-mediated allergy. The level of phospho-STAT3 was significantly elevated in myeloid and T cells after challenge in individuals with symptoms. Mass cytometry indicated preferential activation of nonconventional T-cell populations, including γδ T cells and CD3+CD4–CD8–CD161+ cells; however, the potential sources of IL-17 in PBMCs were primarily CD4+ TH17 cells. Conclusions: These results demonstrate a unique IL-17 signature and activation of innate lymphocytes in FPIES.
AB - Background: Food protein–induced enterocolitis syndrome (FPIES) is a non–IgE-mediated food allergy characterized by profuse vomiting within hours of ingestion of the causative food. We have previously reported that FPIES is associated with systemic innate immune activation in the absence of a detectable antigen-specific antibody or T-cell response. The mechanism of specific food recognition by the immune system remains unclear. Objective: Our aim was to identify immune mechanisms underlying FPIES reactions by proteomic and flow cytometric analysis of peripheral blood. Methods: Children with a history of FPIES underwent supervised oral food challenge. Blood samples were taken at baseline, at symptom onset, and 4 hours after symptom onset. We analyzed samples from 23 children (11 reactors and 12 outgrown). A total of 184 protein markers were analyzed by proximity ligation assay and verified by multiplex immunoassay. Analysis of cell subset activation was performed by mass cytometry and spectral cytometry. Results: Symptomatic FPIES challenge results were associated with significant elevation of levels of cytokines and chemokines, including IL-17 family markers (IL-17A, IL-22, IL-17C, and CCL20) and T-cell activation (IL-2), and innate inflammatory markers (IL-8, oncostatin M, leukemia inhibitory factor, TNF-α, IL-10, and IL-6). The level of the mucosal damage marker regenerating family member 1 alpha (REG1A) was also significantly increased. These biomarkers were not increased in asymptomatic challenges or IgE-mediated allergy. The level of phospho-STAT3 was significantly elevated in myeloid and T cells after challenge in individuals with symptoms. Mass cytometry indicated preferential activation of nonconventional T-cell populations, including γδ T cells and CD3+CD4–CD8–CD161+ cells; however, the potential sources of IL-17 in PBMCs were primarily CD4+ TH17 cells. Conclusions: These results demonstrate a unique IL-17 signature and activation of innate lymphocytes in FPIES.
KW - FPIES
KW - Food protein–induced enterocolitis syndrome
KW - STAT3
KW - T17 cells
KW - inflammation
KW - innate immunity
KW - mucosal barrier
KW - oral food challenge
KW - proteomics
UR - http://www.scopus.com/inward/record.url?scp=85106364236&partnerID=8YFLogxK
U2 - 10.1016/j.jaci.2021.04.012
DO - 10.1016/j.jaci.2021.04.012
M3 - Article
C2 - 33891982
AN - SCOPUS:85106364236
VL - 148
SP - 895-901.e6
JO - Journal of Allergy and Clinical Immunology
JF - Journal of Allergy and Clinical Immunology
SN - 0091-6749
IS - 3
ER -