Age and sex influence antibody profiles associated with tuberculosis progression

Leela R L Davies; Chuangqi Wang; Pia Steigler; Kathryn A Bowman; Stephanie Fischinger; Mark Hatherill; Michelle Fisher; Stanley Kimbung Mbandi; Miguel Rodo; Tom H M Ottenhoff; Hazel M Dockrell; Jayne S Sutherland; Harriet Mayanja-Kizza; W Henry Boom; Gerhard Walzl; Stefan H E Kaufmann; Elisa Nemes; Thomas J Scriba; Douglas Lauffenburger; Galit Alter; Sarah M Fortune

doi:10.1038/s41564-024-01678-x

Age and sex influence antibody profiles associated with tuberculosis progression

Nat Microbiol. 2024 Apr 24. doi: 10.1038/s41564-024-01678-x. Online ahead of print.

Authors

Leela R L Davies^#^{1

2}, Chuangqi Wang^#^{3

4}, Pia Steigler^{5

6}, Kathryn A Bowman^{1

2}, Stephanie Fischinger¹, Mark Hatherill⁵, Michelle Fisher⁵, Stanley Kimbung Mbandi⁵, Miguel Rodo⁵, Tom H M Ottenhoff⁷, Hazel M Dockrell⁸, Jayne S Sutherland⁸, Harriet Mayanja-Kizza⁹, W Henry Boom¹⁰, Gerhard Walzl¹¹, Stefan H E Kaufmann^{12

13

14}, Elisa Nemes⁵, Thomas J Scriba⁵, Douglas Lauffenburger⁴, Galit Alter^{15

16}, Sarah M Fortune¹⁷

Affiliations

¹ Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA.
² Brigham and Women's Hospital, Boston, MA, USA.
³ Department of Immunology and Microbiology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
⁴ Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.
⁵ South African Tuberculosis Vaccine Initiative and Institute of Infectious Disease and Molecular Medicine, Division of Immunology, Department of Pathology, University of Cape Town, Cape Town, South Africa.
⁶ Wellcome Centre for Infectious Diseases Research in Africa, Institute of Infectious Disease and Molecular Medicine and Division of Immunology, Department of Medicine, University of Cape Town, Cape Town, South Africa.
⁷ Department of Infectious Diseases, Leiden University Medical Center, Leiden, the Netherlands.
⁸ Vaccines and Immunity Theme, Medical Research Council Unit The Gambia at the London School of Hygiene and Tropical Medicine, Banjul, The Gambia.
⁹ Department of Medicine and Department of Microbiology, Makerere University, Kampala, Uganda.
¹⁰ Tuberculosis Research Unit, Case Western Reserve University, Cleveland, OH, USA.
¹¹ Department of Science and Technology National Research Foundation Centre of Excellence for Biomedical Tuberculosis Research, South African Medical Research Council Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.
¹² Max Planck Institute for Infection Biology, Berlin, Germany.
¹³ Max Planck Institute for Multidisciplinary Sciences, Göttingen, Germany.
¹⁴ Hagler Institute for Advanced Study, Texas A&M University, College Station, TX, USA.
¹⁵ Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA. galit.alter@modernatx.com.
¹⁶ Moderna Therapeutics, Cambridge, MA, USA. galit.alter@modernatx.com.
¹⁷ Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA, USA. sfortune@hsph.harvard.edu.

^# Contributed equally.

PMID: 38658786
DOI: 10.1038/s41564-024-01678-x

Abstract

Antibody features vary with tuberculosis (TB) disease state. Whether clinical variables, such as age or sex, influence associations between Mycobacterium tuberculosis-specific antibody responses and disease state is not well explored. Here we profiled Mycobacterium tuberculosis-specific antibody responses in 140 TB-exposed South African individuals from the Adolescent Cohort Study. We identified distinct response features in individuals progressing to active TB from non-progressing, matched controls. A multivariate antibody score differentially associated with progression (SeroScore) identified progressors up to 2 years before TB diagnosis, earlier than that achieved with the RISK6 transcriptional signature of progression. We validated these antibody response features in the Grand Challenges 6-74 cohort. Both the SeroScore and RISK6 correlated better with risk of TB progression in adolescents compared with adults, and in males compared with females. This suggests that age and sex are important, underappreciated modifiers of antibody responses associated with TB progression.

Abstract

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