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An In vitro Model to Study Immune Responses of Human Peripheral Blood Mononuclear Cells to Human Respiratory Syncytial Virus Infection
Published on: December 10, 2013
CXCL12 and CXCL13 as potential biomarkers for disease severity and recurrence in respiratory syncytial virus
Lin Zhang1,2, Yuanyu Lv1, Zhiao Du1
1Department of Respiratory Medicine, Children's Hospital of Soochow University, Suzhou, 215003, China.
Insights
Chemokine CXCL12 may predict Respiratory Syncytial Virus (RSV) bronchiolitis severity, while CXCL13 indicates a higher risk of recurrent wheezing in children. These findings aid early clinical evaluation and prognosis for RSV infections.
Area of Science:
- Pediatric Infectious Diseases
- Immunology
- Molecular Biology
Background:
- Respiratory Syncytial Virus (RSV) bronchiolitis is a common childhood illness with significant morbidity.
- Understanding the host immune response, particularly chemokine expression, is crucial for predicting disease severity and long-term outcomes.
- Current diagnostic and prognostic tools for RSV bronchiolitis may benefit from novel biomarkers.
Purpose of the Study:
- To investigate chemokine expression patterns in children with RSV bronchiolitis.
- To evaluate the clinical utility of specific chemokines as early warning indicators for disease severity.
- To assess the prognostic value of chemokines in predicting recurrent wheezing after RSV infection.
Main Methods:
- Blood leukocyte gene expression was analyzed using RNA-sequencing (RNA-seq) in children with RSV bronchiolitis and controls.
- Gene Ontology (GO) and KEGG pathway analyses identified RSV-associated hub genes.
- Flow cytometry was used to confirm chemokine expression levels, and Receiver Operating Characteristic (ROC) curve analysis assessed biomarker utility.
Main Results:
- Twelve hub genes and 712 differentially expressed genes were identified in RSV patients.
- Elevated levels of CXCL2, CXCL12, CXCL13, CCL13, and CCL24 were observed in RSV patients compared to controls.
- CXCL12 levels correlated with moderate-to-severe RSV bronchiolitis (AUC=0.835), and CXCL13 levels were higher in children who later developed recurrent wheezing (AUC=0.851).
Conclusions:
- CXCL12 and CXCL13 demonstrate potential as reliable biomarkers for assessing RSV bronchiolitis severity.
- CXCL13 shows promise as a predictor of recurrent wheezing post-RSV infection.
- These chemokine biomarkers could enhance early clinical evaluation and improve prognostic accuracy for pediatric RSV cases.
Abstract:
To examine chemokine expression in children with Respiratory Syncytial Virus (RSV) bronchiolitis and evaluate its clinical utility for early warning and prognosis. Five hospitalised RSV bronchiolitis children and five matched controls were studied. To validate findings, 50 RSV infants and 30 controls were assessed for recurrent wheezing after 1 year. Blood leukocyte RNA-seq identified RSV-associated hub genes via GO/KEGG analysis, with flow cytometry confirming chemokine expression. Twelve hub genes were identified, with 712 differentially expressed genes (292 upregulated, 420 downregulated). RSV patients showed elevated CXCL2, CXCL12, CXCL13, CCL13, and CCL24 (P < 0.05). CXCL12 was higher in moderate-to-severe cases (Area Under the Curve, AUC = 0.835, 95% CI 0.714-0.956, P < 0.05), while CXCL13 was elevated in recurrent wheezers (AUC = 0.851, 95% CI 0.711-0.991, P < 0.05). CXCL12 predicted severity, and CXCL13 predicted recurrence (ROC-confirmed, P < 0.05). CXCL12 and CXCL13 may serve as biomarkers for assessing RSV bronchiolitis severity and predicting recurrence, aiding early clinical evaluation and prognosis.
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