Children and adolescents with intrathoracic tuberculosis (TB) showed higher levels of macrophages (Mϕs) and dendritic cells (DCs) compared to those with nontuberculosis lung disease, based on new data presented at the Annual Conference of American Association for Bronchology and Interventional Pulmonology.

Interaction between Mycobacterium tuberculosis, Mϕs, and DCs are central to TB pathogenesis and immune protection against TB in pediatric patients, Pankaj C. Vaidya, MD, associate professor of pediatrics at the Postgraduate Institute of Medical Education and Research, Chandigarh, India, wrote.

“Recent work by us and others demonstrate that several C-type lectins, including dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN; CD209), mannose receptor (MR; CD206), and dendritic-associated C-type lectin-2 (Dectin-2) mediate critical interactions between mycobacteria and human monocyte-derived Mϕs and DCs in children with tuberculosis,” the researchers wrote in their abstract. However, the specifics of these activities and their potential clinical implications remain unclear, they noted.

The researchers compared CD209, CD206, and Dectin-2 expression in bronchoalveolar lavage (BAL) cells of 102 children with suspected TB and 102 with other pulmonary disorders who served as control participants, using techniques including flow cytometry, reverse transcription polymerase chain reaction, and immunosorbent assay.

The children with mycobacterial infection included 42 with confirmed TB, 10 with probable TB, and 48 with possible TB. Among these patients, CD209- and Dectin-2-upregulated Mϕs and DCs were present in 46.2% and 7.2% of cases, respectively, compared to 9% and 0%, respectively, of control participants without TB.

The researchers also measured cytokine levels in 71 of the suspected TB cases and 46 control participants, and found that TNF-alpha, interleukin (IL) 6, interferon-gamma, IL-13, IL-23, and IL-17A were significantly higher in cases than in control participants.

Measurement of C-type lectin transcripts (mRNA) was performed in 28 TB cases and 22 control participants, and the average fold change in CD209 transcript expression in patients with definitive TB was significantly higher than control participants (P = .029). However, no significant difference was noted for average fold change expression of CD206 and Dectin-2 expression between the definitive TB cases and control participants, although the expression was elevated in the TB cases, the researchers noted.

Point-of-Care Potential

The findings were limited by the relatively small study population, but the results support data from previous studies, the researchers noted.

The significantly increased expression of CD209 and elevated expression of Dectin-2 suggest potential diagnostic value as biomarkers, the researchers said. “The results also identify a promising assay that could evolve into a point-of-care test for pediatric TB diagnosis,” they concluded.

“In pediatric patients, interaction between the cause of tuberculosis (Mycobacterium tuberculosis) and the immune system plays a role in both protection against TB and disease pathogenesis,” said Max Wayne, MD, an interventional pulmonologist and clinical assistant professor of internal medicine at the University of Michigan Health in Ann Arbor.

The identification of certain molecules that are upregulated in the BAL fluid in children with intrathoracic TB was notable, said Wayne, who was not involved in the study. More research is needed to make the findings applicable to clinical practice, but Wayne agreed with the researchers’ conclusion that the data could be leveraged in the future in point-of-care biomarker testing to help identify pediatric TB.

The study received no outside funding. The researchers had no financial conflicts to disclose. Wayne disclosed serving on a Data and Safety Monitoring Board for Airiver Medical.