Inflammation–Oxidative Stress Axis and its Association with Recurrent Hemolytic Crises in Children with Glucose-6-Phosphate Dehydrogenase Deficiency: Insights from the Oral-Respiratory Bacterial Pathogens
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Abstract
Recurrent bacterial respiratory tract infections (RTIs) are a major trigger of severe oxidative stress and acute hemolysis in children with glucose-6-phosphate dehydrogenase (G6PD) deficiency. This study investigated the association of inflammatory, oxidative stress, and hemolytic biomarkers with recurrent RTIs and evaluated their combined diagnostic performance. This hospital-based cross-sectional analytical study enrolled 175 G6PD-deficient children: 73 with laboratory-confirmed recurrent bacterial RTIs and 102 without recurrent respiratory infections. Serum interleukin-6 (IL-6), procalcitonin (PCT), malondialdehyde (MDA), lactate dehydrogenase (LDH), indirect bilirubin, and haptoglobin were quantified. (ROC) analyses were utilized to address quasi-complete separation and prevent model overfitting. Results showed that Children with recurrent RTIs exhibited significantly higher serum IL-6, PCT, MDA, LDH, and indirect bilirubin levels, alongside depleted haptoglobin concentrations compared to the comparison group (all P<0.001). Multivariable penalized logistic regression identified IL-6 (OR=1.11, P=0.002), PCT (OR=71.94, P<0.001), MDA (OR=11.36, P<0.001), LDH (OR=1.02, P<0.001), indirect bilirubin (OR=15.97, P<0.001), and haptoglobin (OR=0.90, P<0.001) as significant independent correlates of recurrent bacterial RTIs. While PCT achieved the highest individual diagnostic accuracy (AUC=0.886), the internally cross-validated combined biomarker model demonstrated outstanding and robust discriminatory ability (CV-AUC=0.978). In conclusion, recurrent bacterial RTIs in G6PD deficiency provoke a severe, synergistic compounding of systemic inflammation, oxidative stress, and accelerated hemolysis. A combined biomarker panel integrating these pathways offers excellent diagnostic accuracy, providing a robust, non-overfitted clinical tool for early risk stratification and personalized management.
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