Phage-display immunoprecipitation sequencing of the antibody epitope repertoire in inflammatory bowel disease reveals distinct antibody signatures

Bourgonje, Arno R.; Andreu‐Sánchez, Sergio; Vogl, Thomas; Hu, Shixian; Vila, Arnau Vich; Leviatan, Sigal; Kurilshikov, Alexander; Klompus, Shelley; Kalka, Iris; Dullemen, Hendrik M. van; Weinberger, Adina; Visschedijk, Marijn C.; Festen, Eleonora A. M.; Faber, Klaas Nico; Wijmenga, Cisca; Dijkstra, Gerard; Segal, Eran; Fu, Jingyuan; Zhernakova, Alexandra; Weersma, Rinse K.

doi:10.1016/j.immuni.2023.04.017

Cited by 22 publications

(28 citation statements)

References 73 publications

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“…By combining epitope-level and AVARDA analyses, we first investigated the effects of age and sex on the anti-viral antibody repertoire, including antibody levels against 2,608 public peptides and 150 viruses. Regression modeling indicated that antibody reactivity against a wide range of viruses is strongly associated with age, in line with previous studies (Figure 2A) 4,5 . Antibodies against 565 epitopes significantly increased with age, primarily those targeting herpesviruses, as well as the Orthopneumovirus RSV, which infect the human host continuously throughout a lifetime.…”

Section: Resultssupporting

confidence: 91%

“…For example, women have higher titers against human papillomavirus (HPV) 1 and Epstein-Barr virus (EBV) 1,2 and generally generate more robust vaccine responses than men 3 . Population immunity against some herpesviruses, such as HSV-1 and cytomegalovirus (CMV), tends to increase over time due to accumulated exposure 1,2,4,5 . In contrast, viruses that are more prevalent in children (such as respiratory syncytial virus (RSV) and varicella-zoster virus (VZV)) or are a part of childhood immunization schedules (such as measles, mumps, and rubella viruses) tend to be present at high levels in most adults 1,2 .…”

Section: Introductionmentioning

confidence: 99%

“…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%

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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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Section: Resultssupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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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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“…We ran a genome-wide association study (GWAS) on 4,546,708 genotyped and imputed SNPs in 2,815 peptides. To reduce the false discovery rate (FDR) and increase the power of the analysis, we meta-analyzed the results of our LLD GWAS with those of a dataset that used the same PhIPseq libraries in the context of inflammatory bowel disease (IBD) (490 participants), 40 bringing us up to a total of 1,745 individuals (Table S2.2). At the study-wide significance threshold (p < 5.67 3 10 À11 ), we identified multiple signals in three genetic loci associated with 149 antibody-bound peptides.…”

Section: )mentioning

confidence: 99%

Phage display sequencing reveals that genetic, environmental, and intrinsic factors influence variation of human antibody epitope repertoire

et al. 2023

Self Cite

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“…These studies considered genetic, environmental, and intrinsic factors; assessed antibody responses in people with IBD such as Crohn's disease and ulcerative colitis; and compared them with a control group. 211,212 However, despite these advantages, PhIP-Seq has several limitations. It cannot identify autoantibodies that recognize post-translationally modified proteins (i.e., glycosylation isoforms); lack information on post-translational modifications, like sugar moieties; and misses the three-dimensional structure of antigens.…”

Section: Phage Immunoprecipitation Sequencing (Phip-seq)mentioning

confidence: 99%

Exploring Immunome and Microbiome Interplay in Reproductive Health: Current Knowledge, Challenges, and Novel Diagnostic Tools

Lingasamy,

Modhukur,

Mändar

et al. 2023

Semin Reprod Med

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The dynamic interplay between the immunome and microbiome in reproductive health is a complex and rapidly advancing research field, holding tremendously vast possibilities for the development of reproductive medicine. This immunome–microbiome relationship influences the innate and adaptive immune responses, thereby affecting the onset and progression of reproductive disorders. However, the mechanisms governing these interactions remain elusive and require innovative approaches to gather more understanding. This comprehensive review examines the current knowledge on reproductive microbiomes across various parts of female reproductive tract, with special consideration of bidirectional interactions between microbiomes and the immune system. Additionally, it explores innate and adaptive immunity, focusing on immunoglobulin (Ig) A and IgM antibodies, their regulation, self-antigen tolerance mechanisms, and their roles in immune homeostasis. This review also highlights ongoing technological innovations in microbiota research, emphasizing the need for standardized detection and analysis methods. For instance, we evaluate the clinical utility of innovative technologies such as Phage ImmunoPrecipitation Sequencing (PhIP-Seq) and Microbial Flow Cytometry coupled to Next-Generation Sequencing (mFLOW-Seq). Despite ongoing advancements, we emphasize the need for further exploration in this field, as a deeper understanding of immunome–microbiome interactions holds promise for innovative diagnostic and therapeutic strategies for reproductive health, like infertility treatment and management of pregnancy.

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Phage-display immunoprecipitation sequencing of the antibody epitope repertoire in inflammatory bowel disease reveals distinct antibody signatures

Cited by 22 publications

References 73 publications

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

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

Phage display sequencing reveals that genetic, environmental, and intrinsic factors influence variation of human antibody epitope repertoire

Exploring Immunome and Microbiome Interplay in Reproductive Health: Current Knowledge, Challenges, and Novel Diagnostic Tools

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