Extended Data Fig. 5: Sensitivity analysis exploring the role of type specific anti-M protein antibodies in protective immunity.

(a) Absolute change in anti-M IgG Z-scores around 130 culture-confirmed, M/emm-typed S. pyogenes events. Only IgG measurements to M peptides with >45% homologous inhibition in inhibition assays (M1, M4, M44, M75, M89, M25, M87) were included. Paired measurements were categorised as homologous (n = 15), cluster-homologous (n = 104), or unrelated (n = 605) to the M/emm type of the event. Box plots show medians, IQRs, and 1.5×IQR whiskers. Comparisons were made using the Kruskal–Wallis test followed by Dunn’s test with Bonferroni correction (P < 0.05). (b) 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 = 247 measurements, 92 events, 74 participants) and controls (n = 791 measurements, 246 participants). Cluster-related titres were hierarchically assigned: homologous if available, otherwise cluster homologous. (c) Spearman’s correlation between anti-M IgG Z-scores and conserved antigen IgG levels from 969 paired measurements. (d) Forest plot from fully adjusted mixed effects logistic regression models including anti-M IgG (Z-score), conserved antigen IgG (above transition point), age group, sex, and household size. 969 measurements from 859 timepoints and 263 individuals were included. Points represent odds ratios and horizontal bars show 95% Wald confidence intervals. OR = Odds ratio; CI = confidence interval; RLU = Relative Luminex Unit.