Allergenic food protein consumption is associated with systemic IgG antibody responses in non-allergic individuals

Leviatan, Sigal; Vogl, Thomas; Klompus, Shelley; Kalka, Iris; Weinberger, Adina; Segal, Eran

doi:10.1016/j.immuni.2022.11.004

Cited by 19 publications

(33 citation statements)

References 73 publications

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“…In a previous study in the Dutch LLD cohort (13) PhIP-Seq was used to profile two antigen libraries. These libraries consisted of peptides derived from gut microbiota (both commensal species and common pathogens) (11); epitopes from common dietary allergens, phages and viruses; and all B-cell antigens deposited in the IEDB (immune epitope database) (12). Extensive IgG antibody responses against both libraries were observed in the study population (n=1,443) (13), and we used the 2,815 responses frequently shared among participants (detectable in 5–95% of individuals) for further analysis (13) [ Supplementary Table 1 ].…”

Section: Resultsmentioning

confidence: 99%

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Antibody signatures against viruses and microbiome reflect past and chronic exposures and associate with aging and inflammation

Andreu-Sánchez,

Ripoll-Cladellas,

Culinscaia

et al. 2024

Preprint

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Prior encounters with pathogens and other molecules can imprint long-lasting effects on our immune system, potentially influencing future physiological outcomes. However, given the wide range of pathogens and commensal microbes to which humans are exposed, their collective impact on the health and aging processes in the general population is still not fully understood. In this study, we aimed to explore relations between exposures, including to pathogens, microbiome and common allergens, and biological aging and inflammation. We capitalized on an extensive repository of the antibody-binding repertoire against 2,815 microbial, viral, and environmental peptides in a deeply-phenotyped population cohort of 1,443 participants. Utilizing antibody-binding as a proxy for past exposures, we investigated their impact on biological aging markers, immune cell composition and systemic inflammation. This identified that immune response against cytomegalovirus (CMV), rhinovirus and specific gut bacterial species influences the telomere length of different immune cell types. Using blood single-cell RNA-seq measurements, we identified a large effect of CMV infection on the transcriptional landscape of specific immune cells, in particular subpopulations of CD8 and CD4 T-cells. Our work provides a broad examination of the role of past and chronic exposures in biological aging and inflammation, highlighting a role for chronic infections (CMV and Epstein-Barr Virus) and common pathogens (rhinoviruses and adenovirus C).

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Section: Resultsmentioning

confidence: 99%

“…PhIP-Seq profiles were previously generated (13) as described earlier (11,12), following a previously described protocol (59). Two peptide libraries were profiled.…”

Section: Methodsmentioning

confidence: 99%

Antibody signatures against viruses and microbiome reflect past and chronic exposures and associate with aging and inflammation

Andreu-Sánchez,

Ripoll-Cladellas,

Culinscaia

et al. 2024

Preprint

Self Cite

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“…Clarifying these properties may help understand the role of nasopharyngeal IgD responses in immune tolerance as well as inflammation ( 40 , 41 ). Besides broadening our understanding of humoral responses to potential allergens such as common food and airborne proteins ( 42 ), this advance could facilitate the development of novel prognostic tools and therapeutic strategies for allergic disorders. Indeed, allergic children with robust allergen-specific IgD responses show a lower risk of anaphylaxis and increased likelihood of naturally outgrowing allergy ( 43 , 44 ).…”

Section: Discussionmentioning

confidence: 99%

“…We attempted to compensate for this limitation by pooling together non-CVID samples from adult primary immunodeficiency donors with rare gene mutations. Finally, competition with abundant serum IgG pAbs reactive to common environmental antigens ( 42 ) likely limited the binding of serum IgD pAbs to the same antigens.…”

Section: Discussionmentioning

confidence: 99%

Atypical memory B cells form a pre-plasmacellular reservoir for steady-state IgD responses to common nasopharyngeal antigens

Tachó-Piñot,

Bashour,

Filipska

et al. 2023

Preprint

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The human nasopharyngeal mucosa includes organized lymphoepithelial structures continually engaged in frontline immune responses to aerodigestive antigens. Advancing our understanding of these responses might lead to the development of new strategies for the prevention and treatment of common immune disorders such as allergies. Here we identified a hitherto elusive tonsillar subset of atypical IgD class-switched IgD+IgM-memory (IgD-ME) B cells that were clonally related to IgD+IgM−germinal center (IgD-GC) B cells and IgD-secreting IgD+IgM−plasma cells (IgD-PCs) but not anergic IgD+IgM−B cells. Consistent with their pre-plasmacellular properties, IgD-ME B cells served as preferential precursors of IgD-PCs over IgD-GC B cells. IgD antibodies from IgD+IgM−cells acquired reactivity to multiple oral, airborne and commensal antigens through a mutation-dependent pathway involving both innate and adaptive signals. Thus, IgD-ME B cells may form a ready-to-use pre-plasmacellular reservoir for steady-state IgD responses likely aimed at enhancing nasopharyngeal homeostasis.One Sentence SummaryTonsillar atypical memory B cells form a ready-to-use pre-plasmacellular repertoire for IgD responses to common aerodigestive antigens.

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“…This approach was first used to identify plasma autoantibodies using a phage library covering the human peptidome 19,20 . PhIP-seq has since been used to diagnose COVID-19 patients 1321 , profile the humoral immune response against bacteria and food allergens [22][23][24] , and identify antibody repertoire changes in patients with inflammatory bowel disease 5 . The VirScan phage library is a specific implementation of PhIPseq that covers the peptidome of all viruses known to infect humans 25 .…”

Section: Introductionmentioning

confidence: 99%

A systematic investigation into the non-genetic and genetic factors affecting the human anti-viral antibody repertoire

Olin,

Jaquaniello,

Tan

et al. 2023

Preprint

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SummaryImmunoglobulins are among the most important anti-viral effectors of the human immune system. The biological mechanisms underlying antibody production and maintenance are relatively well understood. However, a broader model of how host intrinsic factors and external processes influence humoral responses to viral infections is lacking. Here, we investigate how age, sex, genetics, health-related habits, and immune factors relate to the anti-viral antibody repertoire of healthy humans. We used VirScan, a high-throughput technology based on phage-display immunoprecipitation sequencing (PhIP-seq), to characterize antibody reactivity against more than 90,000 viral epitopes in 1,212 healthy adults of European and African descent. By comparing VirScan with various serological assays, we first show that PhIP-seq-based antibody repertoires recapitulate expected serostatuses and uncover considerable variation in epitope-specific reactivity. In addition to age and sex effects, we find that the antibody repertoire is strongly associated with active smoking, which results in increased antibody levels against rhinoviruses. We provide evidence that individuals born in Central Africa and Europe differ in antigenic reactivity to common herpesviruses by targeting different viral proteins. By comparing antibody repertoires to 169 immune cell parameters, we find that HLA-DR expression in circulating dendritic cells is associated with increased reactivity against EBV. Finally, we conducted a GWAS of antibody binding against more than 2,600 viral peptides. We confirmed a strong effect ofHLAandIGHloci and theFUT2gene and identified new associations between variants in these genes and antibodies against adenoviruses and saliviruses. These findings highlight the determinants of human variation in the humoral response to viruses and broaden perspectives on how the antibody repertoire is generated and maintained.

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Allergenic food protein consumption is associated with systemic IgG antibody responses in non-allergic individuals

Cited by 19 publications

References 73 publications

Antibody signatures against viruses and microbiome reflect past and chronic exposures and associate with aging and inflammation

Antibody signatures against viruses and microbiome reflect past and chronic exposures and associate with aging and inflammation

Atypical memory B cells form a pre-plasmacellular reservoir for steady-state IgD responses to common nasopharyngeal antigens

A systematic investigation into the non-genetic and genetic factors affecting the human anti-viral antibody repertoire

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