Fig. 1: The GAS-specific IgG antigenome.

a Schematic representation of the two-step approach integrating systems antigenomics and systems serology. The systems antigenomics strategy involves the identification of antigenic targets from biochemical fractions of bacterial proteins using host-derived IgG as a guide. Selected antigens are then recombinantly produced and analyzed in a streamlined workflow of various systems serology techniques to deconvolute structural and functional attributes of the antigen-specific IgG. Created in BioRender. Malmström, J. (2025) https://BioRender.com/s45i129. b Schematic summary of the antigen identification workflow used in this study. c Overlap of the bacterial proteins identified across secreted (S), cell wall (CW), and membrane (M) fractions during a typical biochemical fractionation of the SF370 GAS proteome. d Differential protein expression across bacterial fractions. The protein values were normalized using a Z-score normalization and subjected to hierarchical clustering. e Immunoblot analysis of antigens in S, CW, and M fractions of the SF370 GAS strain using IVIG and pooled human plasma. Immunoblots are representative images of at least 2 independent experiments. f Phagocytosis of SF370 bacteria with Xolair, IVIG, and IgG purified from pooled human plasma. Bar graphs represent percentage of THP-1 cells with internalized bacteria for different multiplicity of prey (MOP-ratio of prey to phagocyte)—50, 25, and 12.5. Four technical replicates were used for each condition and statistical significance was assessed by two-way ANOVA with Tukey’s multiple comparisons test, *p < 0.05. Bars represent mean values and error bars represent standard deviation (SD). g Volcano plot displaying the significant antigens recognized by IVIG and (h) pooled human plasma. Statistical significance was determined using a both side t-test with an FDR of 0.05 to correct for multiple comparisons. Source data are provided as a Source Data file.