Fetuin-A As a Biomarker to Predict Invasive Pneumococcal Disease in Children

Background: Streptococcus pneumoniae, a neuraminidase-producing pathogen, can cause invasive pneumococcal disease (IPD) with or without hemolytic uremic syndrome (HUS) in humans. We aimed to identify abundant serum asialoglycoproteins after pneumococcal neuraminidase treatment. We hypothesized that serum sialoglycoproteins such as fetuin-A can serve as a biomarker to predict IPD or HUS. Methods & Materials: We constructed serum sialoglycoprotein profiles before and after pneumococcal neuraminidase treatment using proteomic approach. We analyzed the clinical characteristics and serum samples from 46 pediatric patients with pneumococcal infection to verify the predictive role of fetuin-A in IPD. Serum fetuin-A levels were determined by enzyme-linked immunosorbent assay. Results: Fetuin A was identified after neuraminidase treatment and lectin capture. Bovine fetuin inhibited the activity of neuraminidases with IC50 at 2.59 mg/mL for NanA, 2 mg/mL for NanB and 1.2 mg/mL for NanC. Mean fetuin-A levels in the HUS patients was significantly lower (207 ± 80 mg/L, p < 0.001) than in patients with lobar pneumonia (610 ± 190 mg/L) as well as the healthy controls (630 ± 250 mg/L). In comparing HUS with necrotizing pneumonia and lobar pneumonia, the ROC area under the curve was 0.842; a cutoff value of 298 mg/L yielded sensitivity of 92.9% (95% CI: 68.5%–98.7%) and specificity of 71.9% (95% CI: 54.6%-84.4%). Conclusion: By qualitative and quantitative analysis of serum fetuin-A in pneumococcal infections, we may identify complicated pneumonia with or without HUS caused by S. pneumoniae. Serial measurements of fetuin-A also has the potential to reflect patients’ response to therapy and recovery from IPD. We recommend addition of fetuin-A to the panel of biomarkers currently used for severe IPD.