Biology subjects

Baatyrbek kyzy, A.

Publications and source records attributed to Baatyrbek kyzy, A..

2 recordsLinked to original sources

bioRxiv2024

Use of Antibody Structural Information in Disease Prediction Models Reveals Antigen Specific B Cell Receptor Sequences in Bulk Repertoire Data

Convergent antibodies are highly similar antibodies elicited in multiple individuals in response to the same antigen. Convergent antibodies provide insight into shared immunological responses and show great promise as diagnostic biomarkers. They have typically been identified using methods that consider the amino acid sequence of the third complementarity-determining region (CDR3) of immunoglobulin heavy chain (IgH). In this study, we extend the definition of convergent antibodies to use structural information about the three IgH CDR regions (CDR1-3). We benchmark the performance of both definitions of convergence by their ability to predict disease status from bulk IgH sequencing data for two different diseases (HIV infection and food sensitization). We show that using predicted structural information outperforms prior approaches for the prediction of food sensitization status and performs on par for HIV infection status. Additionally, the structurally convergent antibody groups driving HIV prediction are from known HIV binders. Thus, the use of structural information allows for the identification of antigen specific antibody groups from bulk IgH sequencing data.

immunology↗

bioRxiv2023

B cell repertoire in children with skin barrier dysfunction supports altered IgE maturation associated with allergic food sensitization

IgE B cells produce antibodies responsible for the inappropriate specificity seen in allergic disease. In this study, we sequence antibody gene repertoires from a large, well-characterized early life cohort at risk for developing food allergy. We found that food allergen sensitization was associated with lower IgE mutation frequencies that was abrogated in children living with a pet dog, suggesting potential molecular mechanisms underlying the hygiene hypothesis (i.e., protective effects of pet ownership and non-antiseptic environs reported for allergic disease). We also observed increased IgE diversity and increased isotype-switching to IgE, suggesting that B cell development is altered in those with food allergen sensitizations relative to those without. IgE diversity was even more extreme in subjects who were highly likely to be peanut allergic. Unlike food antigen sensitization, we detected no effect of aeroallergen sensitization on IgE mutation levels and diversity. Consistent patterns of antibody rearrangement were associated with food allergen sensitization. These results have important implications for the allergic response driven by mast cells and basophils and the underlying drivers of the atopic march.

immunology↗