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. 2024 Apr 24;9(6):1513–1525. doi: 10.1038/s41564-024-01678-x

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© The Author(s) 2024

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 1 — a, Serum collected longitudinally from a cohort of South African adolescents who later progressed to active TB disease (n = 36) or who maintained asymptomatic infection (n = 104). For analyses in the current study, progressors were aligned by time of diagnosis and non-progressors by time of enrolment. b, Systems serologic assays performed against a panel of Mtb antigens, including the selection of antibody isotype and subclasses, the binding of Fcγ receptors, the binding to Fc of lectins SNA (recognizes sialic acid) and RCA (recognizes galactose), and the ability to recruit antibody-mediated cellular phagocytosis (ADCP) and neutrophil phagocytosis (ADNP). For each indicated assay, values for each individual were averaged over time. Each heatmap represents log₂(median value in progressors/median value in non-progressors). The statistical significance of the differences between progressors and non-progressors was measured by two-sided Mann–Whitney test followed by Benjamini–Hochberg (BH) correction for multiple comparisons. *P < 0.05; **P < 0.01. c, Mixed-effects linear modelling to evaluate the association between antibody features and progressor status by controlling age, sex, ethnicity, school code and time of sample collection. Likelihood ratio test was used to compare the two paired models, and P values were corrected for multiple comparisons by the BH method. The x axis indicates the effect size as a normalized coefficient of the variable of progression, and the y axis −log₁₀ of the adjusted P values. The dotted line represents the corrected P value of 0.05. d, Raw values of LAM-specific IgG measurements for all individuals plotted over time from enrolment (non-progressors, teal) or time to TB (progressors, orange). The solid lines indicate a smooth of median values, using a generalized additive model, and the grey shading indicates one standard deviation. e–g, Plots for PPD-specific IgA1 (e), LAM-specific antibody binding of FcγR2A (f) and TbAd-specific antibody binding of FcγR3A (g).

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