Distinct antibody-based signatures and functionality distinguish latent and active pediatric tuberculosis Article Swipe
Nadege Nziza
,
Wonyeong Jung
,
Tina Chen
,
Yixiang Deng
,
Kees L. M. C. Franken
,
Tom H. M. Ottenhoff
,
Sarah Kiguli
,
Deborah A. Lewinsohn
,
W. Henry Boom
,
Harriet Mayanja-Kizza
,
Mary Nsereko
,
Sarah M. Fortune
,
Catherine M. Stein
,
Ryan P. McNamara
,
Galit Alter
,
Christina Lancioni
·
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1101/2025.07.21.665984
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1101/2025.07.21.665984
Background Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), is among the leading causes of death from an infectious agent among children worldwide. Children represent a particularly vulnerable population due to the greater challenges in diagnosis and the higher risk of progression to severe forms of the disease. However, whether different pediatric outcomes relate to distinct immunologic responses remains incompletely understood. Emerging data suggest that Mtb-specific humoral immune responses represent a correlate of protection against Mtb both following natural infection and vaccination. Methods To determine if immune profiles can distinguish children across the spectrum from Mtb infection to TB disease, as well as children with TB from non-TB lower respiratory tract infection, we mapped the humoral immune response across a panel of 4 dozen Mtb antigens across children presenting with symptoms of active TB (ATB), children with evidence of latent TB infection (LTBI) and children exhibiting non-TB lower respiratory tract infection (non-TB LRTI). Using a custom Luminex assay, Mtb-specific antibody subclass/isotype, Fc receptor (FcR) binding profiles, and functions were profiled across the pediatric groups. Findings A robust humoral immune response was observed in children with active TB compared to non-TB LRTI, marked by a strong IgA response, that exhibited high FcαR binding. Conversely, children with LTBI uniquely elicited Mtb-specific antibodies with enhanced opsinophagocytic FcγR2A binding, as well as a higher capacity to activate NK cells and neutrophils. Interpretation There are significant differences in humoral immune profiles across the landscape of pediatric TB, potentially contributing to differential mycobacterial control, and highlighting biomarkers that could guide both diagnostic and therapeutic approaches. Funding US National Institutes of Health.
Related Topics
Concepts
Latent tuberculosis
Active tuberculosis
Antibody
Tuberculosis
Computational biology
Computer science
Immunology
Medicine
Mycobacterium tuberculosis
Biology
Pathology
Metadata
- Type
- preprint
- Language
- en
- Landing Page
- https://doi.org/10.1101/2025.07.21.665984
- https://www.biorxiv.org/content/biorxiv/early/2025/07/24/2025.07.21.665984.full.pdf
- OA Status
- green
- References
- 29
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4412628026
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4412628026Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.1101/2025.07.21.665984Digital Object Identifier
- Title
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Distinct antibody-based signatures and functionality distinguish latent and active pediatric tuberculosisWork title
- Type
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preprintOpenAlex work type
- Language
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enPrimary language
- Publication year
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2025Year of publication
- Publication date
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2025-07-24Full publication date if available
- Authors
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Nadege Nziza, Wonyeong Jung, Tina Chen, Yixiang Deng, Kees L. M. C. Franken, Tom H. M. Ottenhoff, Sarah Kiguli, Deborah A. Lewinsohn, W. Henry Boom, Harriet Mayanja-Kizza, Mary Nsereko, Sarah M. Fortune, Catherine M. Stein, Ryan P. McNamara, Galit Alter, Christina LancioniList of authors in order
- Landing page
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https://doi.org/10.1101/2025.07.21.665984Publisher landing page
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https://www.biorxiv.org/content/biorxiv/early/2025/07/24/2025.07.21.665984.full.pdfDirect link to full text PDF
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YesWhether a free full text is available
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greenOpen access status per OpenAlex
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https://www.biorxiv.org/content/biorxiv/early/2025/07/24/2025.07.21.665984.full.pdfDirect OA link when available
- Concepts
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Latent tuberculosis, Active tuberculosis, Antibody, Tuberculosis, Computational biology, Computer science, Immunology, Medicine, Mycobacterium tuberculosis, Biology, PathologyTop concepts (fields/topics) attached by OpenAlex
- Cited by
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0Total citation count in OpenAlex
- References (count)
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29Number of works referenced by this work
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10Other works algorithmically related by OpenAlex
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| abstract_inverted_index.respiratory | 109, 148 |
| abstract_inverted_index.significant | 230 |
| abstract_inverted_index.therapeutic | 257 |
| abstract_inverted_index.understood. | 60 |
| abstract_inverted_index.Mtb-specific | 65, 158, 208 |
| abstract_inverted_index.Tuberculosis | 2 |
| abstract_inverted_index.contributing | 243 |
| abstract_inverted_index.differential | 245 |
| abstract_inverted_index.highlighting | 249 |
| abstract_inverted_index.incompletely | 59 |
| abstract_inverted_index.neutrophils. | 226 |
| abstract_inverted_index.particularly | 26 |
| abstract_inverted_index.tuberculosis | 7 |
| abstract_inverted_index.vaccination. | 81 |
| abstract_inverted_index.Mycobacterium | 6 |
| abstract_inverted_index.mycobacterial | 246 |
| abstract_inverted_index.Interpretation | 227 |
| abstract_inverted_index.opsinophagocytic | 212 |
| abstract_inverted_index.subclass/isotype, | 160 |
| cited_by_percentile_year | |
| corresponding_author_ids | https://openalex.org/A5029065307 |
| countries_distinct_count | 3 |
| institutions_distinct_count | 16 |
| corresponding_institution_ids | https://openalex.org/I165690674 |
| citation_normalized_percentile.value | 0.36357102 |
| citation_normalized_percentile.is_in_top_1_percent | False |
| citation_normalized_percentile.is_in_top_10_percent | False |