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Dissecting the properties of circulating IgG against streptococcal pathogens through a combined systems antigenomics-serology workflow

Gomez Toledo, Alejandro LU ; Chowdhury, Sounak LU ; Hjortswang, Elisabeth LU orcid ; Sorrentino, James T ; Lewis, Nathan E ; Bläckberg, Anna LU ; Ekström, Simon LU ; Kjellström, Sven LU ; Izadi, Arman LU and Olofsson, Berit LU orcid , et al. (2025) In Nature Communications 16. p.1-16
Abstract

This study showcases an integrative mass spectrometry-based strategy combining systems antigenomics and systems serology to characterize human antibodies in clinical samples. This strategy involves using antibodies circulating in plasma to affinity-enrich antigenic proteins in biochemically fractionated pools of bacterial proteins, followed by their identification and quantification using mass spectrometry. A selected subset of the identified antigens is then expressed recombinantly to isolate antigen-specific IgG, followed by characterization of the structural and functional properties of these antibodies. We focused on Group A streptococcus (GAS), a major human pathogen lacking an approved vaccine. The data shows that both healthy and... (More)

This study showcases an integrative mass spectrometry-based strategy combining systems antigenomics and systems serology to characterize human antibodies in clinical samples. This strategy involves using antibodies circulating in plasma to affinity-enrich antigenic proteins in biochemically fractionated pools of bacterial proteins, followed by their identification and quantification using mass spectrometry. A selected subset of the identified antigens is then expressed recombinantly to isolate antigen-specific IgG, followed by characterization of the structural and functional properties of these antibodies. We focused on Group A streptococcus (GAS), a major human pathogen lacking an approved vaccine. The data shows that both healthy and GAS-infected individuals have circulating IgG against conserved streptococcal proteins, including toxins and virulence factors. The antigenic breadth of these antibodies remains relatively constant across healthy individuals but changes considerably in GAS bacteremia. Moreover, antigen-specific IgG analysis reveals individual variation in titers, subclass distributions, and Fc-signaling capacity, despite similar epitope and Fc-glycosylation patterns. Finally, we show that GAS antibodies may cross-react with Streptococcus dysgalactiae (SD), a bacterial pathogen that occupies similar niches and causes comparable infections. Collectively, our results highlight the complexity of GAS-specific antibody responses and the versatility of our methodology to characterize immune responses to bacterial pathogens.

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publishing date
type
Contribution to journal
publication status
published
subject
keywords
Humans, Immunoglobulin G/blood, Streptococcal Infections/immunology, Antigens, Bacterial/immunology, Streptococcus pyogenes/immunology, Antibodies, Bacterial/immunology, Bacterial Proteins/immunology, Cross Reactions/immunology, Streptococcus/immunology, Female, Workflow, Adult, Male, Mass Spectrometry
in
Nature Communications
volume
16
article number
1942
pages
1 - 16
publisher
Nature Publishing Group
external identifiers
  • pmid:39994218
  • scopus:85218502847
ISSN
2041-1723
DOI
10.1038/s41467-025-57170-5
language
English
LU publication?
yes
additional info
© 2025. The Author(s).
id
33e1c92e-69a5-44a4-b306-30b03dac2ef9
date added to LUP
2025-02-27 04:38:17
date last changed
2025-07-14 14:40:40
@article{33e1c92e-69a5-44a4-b306-30b03dac2ef9,
  abstract     = {{<p>This study showcases an integrative mass spectrometry-based strategy combining systems antigenomics and systems serology to characterize human antibodies in clinical samples. This strategy involves using antibodies circulating in plasma to affinity-enrich antigenic proteins in biochemically fractionated pools of bacterial proteins, followed by their identification and quantification using mass spectrometry. A selected subset of the identified antigens is then expressed recombinantly to isolate antigen-specific IgG, followed by characterization of the structural and functional properties of these antibodies. We focused on Group A streptococcus (GAS), a major human pathogen lacking an approved vaccine. The data shows that both healthy and GAS-infected individuals have circulating IgG against conserved streptococcal proteins, including toxins and virulence factors. The antigenic breadth of these antibodies remains relatively constant across healthy individuals but changes considerably in GAS bacteremia. Moreover, antigen-specific IgG analysis reveals individual variation in titers, subclass distributions, and Fc-signaling capacity, despite similar epitope and Fc-glycosylation patterns. Finally, we show that GAS antibodies may cross-react with Streptococcus dysgalactiae (SD), a bacterial pathogen that occupies similar niches and causes comparable infections. Collectively, our results highlight the complexity of GAS-specific antibody responses and the versatility of our methodology to characterize immune responses to bacterial pathogens.</p>}},
  author       = {{Gomez Toledo, Alejandro and Chowdhury, Sounak and Hjortswang, Elisabeth and Sorrentino, James T and Lewis, Nathan E and Bläckberg, Anna and Ekström, Simon and Kjellström, Sven and Izadi, Arman and Olofsson, Berit and Nordenfelt, Pontus and Malmström, Lars and Rasmussen, Magnus and Malmström, Johan}},
  issn         = {{2041-1723}},
  keywords     = {{Humans; Immunoglobulin G/blood; Streptococcal Infections/immunology; Antigens, Bacterial/immunology; Streptococcus pyogenes/immunology; Antibodies, Bacterial/immunology; Bacterial Proteins/immunology; Cross Reactions/immunology; Streptococcus/immunology; Female; Workflow; Adult; Male; Mass Spectrometry}},
  language     = {{eng}},
  month        = {{02}},
  pages        = {{1--16}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Nature Communications}},
  title        = {{Dissecting the properties of circulating IgG against streptococcal pathogens through a combined systems antigenomics-serology workflow}},
  url          = {{http://dx.doi.org/10.1038/s41467-025-57170-5}},
  doi          = {{10.1038/s41467-025-57170-5}},
  volume       = {{16}},
  year         = {{2025}},
}