Distinct antibody-based signatures and functionality distinguish latent and active pediatric tuberculosis

Area of Science:

• Immunology
• Infectious Diseases
• Pediatrics

Background:

• Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), is a leading infectious cause of death in children globally.
• Children are a vulnerable population for TB due to diagnostic challenges and rapid disease progression.
• Understanding distinct immunologic responses in pediatric TB is crucial for improved outcomes.

Purpose of the Study:

• To investigate if distinct immune profiles differentiate children with Mtb infection from those with active TB disease.
• To distinguish between children with active TB and those with non-TB lower respiratory tract infections (LRTI).
• To identify potential immune biomarkers for pediatric TB diagnosis and management.

Main Methods:

• Mapped humoral immune responses across a panel of Mtb antigens in pediatric groups.
• Utilized a custom Luminex assay to profile Mtb-specific antibody subclass/isotype, Fc receptor (FcR) binding, and functions.
• Compared immune profiles in children with active TB (ATB), latent TB infection (LTBI), and non-TB LRTI.

Main Results:

• Children with active TB showed robust humoral responses, including a strong IgA response with high FcαR binding, compared to non-TB LRTI.
• Children with LTBI uniquely produced Mtb-specific antibodies with enhanced FcγR2A binding and greater capacity to activate NK cells and neutrophils.
• Significant differences in humoral immune profiles were observed across the spectrum of pediatric TB.

Conclusions:

• Humoral immune profiles vary significantly in pediatric TB, influencing mycobacterial control.
• Identified potential biomarkers that could inform diagnostic and therapeutic strategies for pediatric TB.
• Further research into these immune signatures may lead to improved management of childhood TB.