Plasma glial fibrillary acidic protein levels in children with sickle cell disease

Abstract

To determine if glial fibrillary acidic protein (GFAP) is associated with brain injury in children with sickle cell disease (SCD), we measured plasma GFAP among cross-sectional groups of unselected children with SCD, subsets of children with SCD and normal brain MRI or MRI evidence of cerebral infarct, healthy pediatric controls, and adults with brain injury. Children with SCD had higher plasma GFAP than healthy pediatric controls (mean concentrations 0.14 ± 0.37 vs. 0.07 ± 0.08 ng/mL; P 5 0.003); also, 16.0% (16/100) of children with SCD and cerebral infarct had GFAP elevations above the 95th percentile of healthy pediatric controls (P 5 0.04). Although not statistically significant, children with SCD and cerebral infarct had more elevated GFAP levels than with SCD and no infarct (16/100, 16.0% vs. 14/168, 8.3%; P 5 0.07). Children with SCD and acute brain ischemia had a higher proportion of elevated GFAP than SCD children with normal MRI (3/6, 50% vs.8.3%; P 5 0.01). GFAP was associated with elevated systolic blood pressure in the preceding year and correlated positively with white blood cell count and negatively with age and performance IQ. Plasma GFAP is elevated among children with SCD and may be associated with subclinical brain injury.

Trial registration: ClinicalTrials.gov NCT00072761.

Conflict of interest statement

Conflict of interest disclosures:

The authors do not have any conflicts to disclose.

Figures

Figure 1. Log plot of plasma GFAP concentrations in children with SCD and controls

(A) Displayed are GFAP concentrations in healthy pediatric controls (n=60), children 5-14 years old with HbSS and HbSβ° – thalassemia (n=295); and adults with overt brain injury: stroke (n=12), brain biopsy (n=3), or partial brain resection (n=13) 1-22 days prior. There is one GFAP observation per subject. Bars represent mean values. (B) Log plot of plasma GFAP concentrations in subsets of SCD children with no infarct by brain MRI (n=168), cerebral infarct by brain MRI (n=100), and MRI diffusion weighted imaging (DWI) evidence of acute infarct (n=6) and plasma drawn within 21 days of the MRI. The dashed line marks the 95th percentile value among 60 healthy pediatric controls, and percentages list the proportions above the 95th percentile of healthy controls.

Figure 1. Log plot of plasma GFAP concentrations in children with SCD and controls

(A) Displayed are GFAP concentrations in healthy pediatric controls (n=60), children 5-14 years old with HbSS and HbSβ° – thalassemia (n=295); and adults with overt brain injury: stroke (n=12), brain biopsy (n=3), or partial brain resection (n=13) 1-22 days prior. There is one GFAP observation per subject. Bars represent mean values. (B) Log plot of plasma GFAP concentrations in subsets of SCD children with no infarct by brain MRI (n=168), cerebral infarct by brain MRI (n=100), and MRI diffusion weighted imaging (DWI) evidence of acute infarct (n=6) and plasma drawn within 21 days of the MRI. The dashed line marks the 95th percentile value among 60 healthy pediatric controls, and percentages list the proportions above the 95th percentile of healthy controls.

Figure 2. Temporal relationship of plasma GFAP levels to diagnosis of acute cerebral infarct

Diffusion weighted brain MRI imaging (DWI) was positive in six children with SCD. Blood samples were drawn either before or after brain MRI. The dashed line marks the 95th percentile value among 60 healthy pediatric controls. The shaded area indicates the approximate age of infarct, as estimated by DWI. The child with a sample drawn 15 days prior to MRI was ultimately determined to have an overt stroke. All children were clinically asymptomatic at the time of MRI screening and sample acquisition.