Fig. 5: Exploring the role of type-specific anti-M protein antibodies in protective immunity.

a, Cross-sectional profiles of anti-M IgG z-scores at baseline in participants without events (n = 402), stratified by age in years. b, MFIs (adjusted for dilution) for each M peptide at baseline, showing relative IgG abundance across peptides. c, Absolute change in anti-M IgG z-scores around 130 culture-confirmed, M/emm typed S. pyogenes events. Paired measurements were categorized as homologous (n = 40), cluster-homologous (n = 202) or unrelated (n = 1,757) to the emm type of the event. Box plots show medians, IQRs and 1.5× IQR whiskers. Kruskal–Wallis and post hoc Dunn’s tests with Bonferroni correction were used for comparison (*P < 0.05 and **P < 0.01). d, Logistic mixed-effects models were used to assess the association between M/emm cluster-related anti-M IgG z-score and the odds of an event within 45 days. Anti-M IgG (z-scores) before, during and after culture-confirmed M/emm typed events in both cases (n = 378 measurements, 143 events, 103 participants) and household controls (n = 1,366 measurements from 293 participants) were identified against the emm cluster-related M peptide to the M/emm type of the event. The cluster-related IgG level was assigned hierarchically with the homologous titer included where available; otherwise, the emm cluster homologous titer was selected. OR for each z-score change, 95% CIs and P values from two-sided logistic regression models are displayed (*P < 0.05). e, Spearman’s correlation between z-score normalized anti-M IgG and conserved antigen IgG levels, based on 1,651 paired measurements. f, Tile plot showing predicted probabilities of an event within 45 days by anti-M IgG (z-score) and conserved antigen IgG above the transition point. Logistic mixed-effects models included both antibody types. g, Forest plot from fully adjusted logistic mixed-effects models (n = 1,652 samples from 307 individuals), showing ORs (points) and 95% Wald CIs (horizontal lines) for anti-M IgG and conserved antigen IgG above the transition point. Models were adjusted for age, sex and household size. NS, not significant; ref, reference.