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Plasma chemokines as immune biomarkers for diagnosis of pediatric tuberculosis
Nathella Pavan Kumar1, Syed Hissar2, Kannan Thiruvengadam3
1ICMR-National Institute for Research in Tuberculosis, Chennai, India. pavankumarn@nirt.res.in.
Insights
Plasma chemokines like CCL1, CXCL1, and CXCL10 show promise as biomarkers for diagnosing pediatric tuberculosis (TB). These markers accurately distinguish active TB cases from unlikely TB, aiding in early detection and treatment.
Area of Science:
- Immunology
- Pediatric Infectious Diseases
- Biomarker Discovery
Background:
- Diagnosing tuberculosis (TB) in children is difficult due to low bacterial loads and challenges in microbiological confirmation.
- Plasma chemokines are being investigated as potential biomarkers for improved pediatric TB diagnosis.
Purpose of the Study:
- To measure plasma chemokine levels as diagnostic biomarkers for pediatric tuberculosis.
- To evaluate the accuracy of specific chemokines in differentiating active TB from unlikely TB in children.
Main Methods:
- A prospective case-control study involving children with confirmed, unconfirmed, and unlikely TB.
- Multiplex assays were used to analyze plasma levels of CC and CXC chemokines.
Main Results:
- Significantly higher baseline levels of CCL1, CCL3, CXCL1, CXCL2, and CXCL10 were observed in children with active TB compared to those with unlikely TB.
- CCL1, CXCL1, and CXCL10 demonstrated >80% sensitivity and specificity in distinguishing active TB. Combined analysis (combiROC) and classification tree models achieved >90% accuracy.
- Chemokine levels decreased significantly after anti-TB treatment, indicating their role in disease activity.
Conclusions:
- A baseline chemokine signature including CCL1, CXCL1, and CXCL10 can serve as an accurate biomarker for diagnosing pediatric tuberculosis.
- These chemokines offer a promising non-invasive method for improving TB diagnosis in children.
Background:
Diagnosing tuberculosis (TB) in children is challenging due to paucibacillary disease, and lack of ability for microbiologic confirmation. Hence, we measured the plasma chemokines as biomarkers for diagnosis of pediatric tuberculosis.
Methods:
We conducted a prospective case control study using children with confirmed, unconfirmed and unlikely TB. Multiplex assay was performed to examine the plasma CC and CXC levels of chemokines.
Results:
Baseline levels of CCL1, CCL3, CXCL1, CXCL2 and CXCL10 were significantly higher in active TB (confirmed TB and unconfirmed TB) in comparison to unlikely TB children. Receiver operating characteristics curve analysis revealed that CCL1, CXCL1 and CXCL10 could act as biomarkers distinguishing confirmed or unconfirmed TB from unlikely TB with the sensitivity and specificity of more than 80%. In addition, combiROC exhibited more than 90% sensitivity and specificity in distinguishing confirmed and unconfirmed TB from unlikely TB. Finally, classification and regression tree models also offered more than 90% sensitivity and specificity for CCL1 with a cutoff value of 28 pg/ml, which clearly classify active TB from unlikely TB. The levels of CCL1, CXCL1, CXCL2 and CXCL10 exhibited a significant reduction following anti-TB treatment.
Conclusion:
Thus, a baseline chemokine signature of CCL1/CXCL1/CXCL10 could serve as an accurate biomarker for the diagnosis of pediatric tuberculosis.
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