Dataset Information

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.

SUBMITTER: Savage WJ

PROVIDER: S-EPMC3870012 | biostudies-literature | 2011 May

REPOSITORIES: biostudies-literature

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

Savage William J WJ Barron-Casella Emily E Fu Zongming Z Dulloor Pratima P Williams Lisa L Crain Barbara J BJ White Desiree A DA Jennings Jacky M JM Van Eyk Jennifer E JE Debaun Michael R MR Everett Allen A Casella James F JF

American journal of hematology 20110501 5

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 ...[more]

PMID: 21523806

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Project description:ImportanceGlial fibrillary acidic protein (GFAP) is a marker of reactive astrogliosis that increases in the cerebrospinal fluid (CSF) and blood of individuals with Alzheimer disease (AD). However, it is not known whether there are differences in blood GFAP levels across the entire AD continuum and whether its performance is similar to that of CSF GFAP.ObjectiveTo evaluate plasma GFAP levels throughout the entire AD continuum, from preclinical AD to AD dementia, compared with CSF GFAP.Design, setting, and participantsThis observational, cross-sectional study collected data from July 29, 2014, to January 31, 2020, from 3 centers. The Translational Biomarkers in Aging and Dementia (TRIAD) cohort (Montreal, Canada) included individuals in the entire AD continuum. Results were confirmed in the Alzheimer's and Families (ALFA+) study (Barcelona, Spain), which included individuals with preclinical AD, and the BioCogBank Paris Lariboisière cohort (Paris, France), which included individuals with symptomatic AD.Main outcomes and measuresPlasma and CSF GFAP levels measured with a Simoa assay were the main outcome. Other measurements included levels of CSF amyloid-β 42/40 (Aβ42/40), phosphorylated tau181 (p-tau181), neurofilament light (NfL), Chitinase-3-like protein 1 (YKL40), and soluble triggering receptor expressed on myeloid cells 2 (sTREM2) and levels of plasma p-tau181 and NfL. Results of amyloid positron emission tomography (PET) were available in TRIAD and ALFA+, and results of tau PET were available in TRIAD.ResultsA total of 300 TRIAD participants (177 women [59.0%]; mean [SD] age, 64.6 [17.6] years), 384 ALFA+ participants (234 women [60.9%]; mean [SD] age, 61.1 [4.7] years), and 187 BioCogBank Paris Lariboisière participants (116 women [62.0%]; mean [SD] age, 69.9 [9.2] years) were included. Plasma GFAP levels were significantly higher in individuals with preclinical AD in comparison with cognitively unimpaired (CU) Aβ-negative individuals (TRIAD: Aβ-negative mean [SD], 185.1 [93.5] pg/mL, Aβ-positive mean [SD], 285.0 [142.6] pg/mL; ALFA+: Aβ-negative mean [SD], 121.9 [42.4] pg/mL, Aβ-positive mean [SD], 169.9 [78.5] pg/mL). Plasma GFAP levels were also higher among individuals in symptomatic stages of the AD continuum (TRIAD: CU Aβ-positive mean [SD], 285.0 [142.6] pg/mL, mild cognitive impairment [MCI] Aβ-positive mean [SD], 332.5 [153.6] pg/mL; AD mean [SD], 388.1 [152.8] pg/mL vs CU Aβ-negative mean [SD], 185.1 [93.5] pg/mL; Paris: MCI Aβ-positive, mean [SD], 368.6 [158.5] pg/mL; AD dementia, mean [SD], 376.4 [179.6] pg/mL vs CU Aβ-negative mean [SD], 161.2 [67.1] pg/mL). Plasma GFAP magnitude changes were consistently higher than those of CSF GFAP. Plasma GFAP more accurately discriminated Aβ-positive from Aβ-negative individuals than CSF GFAP (area under the curve for plasma GFAP, 0.69-0.86; area under the curve for CSF GFAP, 0.59-0.76). Moreover, plasma GFAP levels were positively associated with tau pathology only among individuals with concomitant Aβ pathology.Conclusions and relevanceThis study suggests that plasma GFAP is a sensitive biomarker for detecting and tracking reactive astrogliosis and Aβ pathology even among individuals in the early stages of AD.

Project description:Background: Neurofilament light chain (NfL) and glial fibrilliary acidic protein (GFAP) have been suggested to be biomarkers of the pathophysiological process of neuromyelitis optica spectrum disorders (NMOSD), but the relationship between the plasma levels of these molecules with disease activity and treatment is incompletely understood. Objective: To investigate the treatment effects of disease-modifying drugs on plasma neurofilament light chain (pNfL) and plasma glial fibrillary acidic protein (pGFAP) and explore the predictive value of pNfL and pGFAP in the activity of NMOSD. Methods: pNfL and pGFAP levels were measured using single-molecule arrays in 72 patients with NMOSD and 38 healthy controls (HCs). Patients with NMOSD received tocilizumab (n = 29), rituximab (n = 23), oral prednisone (n = 16), and oral azathioprine or mycophenolate mofetil (n = 4). Results: NMOSD patients had significantly higher pNfL and pGFAP levels than HCs (pNfL, 18.3 (11.2–39.3) versus 11.5 (7.0–23.3) pg/mL; p = 0.001; pGFAP, 149.7 (88.6–406.5) versus 68.7 (59.4–80.8) pg/mL; p < 0.001). Multivariable regression analyses indicated that baseline pNfL concentration was associated with age (p = 0.017), Expanded Disability Status Scale (EDSS) score (p = 0.002), and recent relapses (p < 0.001). Baseline pGFAP concentration was also associated with EDSS (p < 0.001) and recent relapses (p < 0.001). Compared with prednisone, tocilizumab and rituximab significantly reduced pNfL [tocilizumab, exp(β), 0.65; 95% confidence interval (CI), 0.56–0.75; p < 0.001; rituximab, exp(β), 0.79; 95% CI = 0.68–0.93; p = 0.005] and pGFAP levels [tocilizumab, exp(β), 0.64; 95% CI, 0.51–0.80; p < 0.001; rituximab, exp(β), 0.77; 95% CI, 0.61–0.98; p = 0.041] at the end of the study. The pNfL levels in the tocilizumab and rituximab groups were reduced to those of HCs [tocilizumab, 8.5 (7.06–17.90) pg/mL; p = 0.426; rituximab, 14.0 (9.94–21.80) pg/mL; p = 0.216]. However, the pGFAP levels did not decrease to those of HCs in NMOSD patients at the end of study [tocilizumab, 88.9 (63.4–131.8) pg/mL; p = 0.012; rituximab, 141.7 (90.8–192.7) pg/mL; p < 0.001]. Conclusion: pNfL and pGFAP may serve as biomarkers for NMOSD disease activity and treatment effects.

Dataset Information

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

Publications

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

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