title: Antioxidant Capacity and Superoxide Dismutase Activity in Adrenoleukodystrophy.
abstract: X-linked adrenoleukodystrophy (ALD) may switch phenotype to the fatal cerebral form (ie, cerebral ALD [cALD]), the cause of which is unknown. Determining differences in antioxidant capacity and superoxide dismutase (SOD) levels between phenotypes may allow for the generation of a clinical biomarker for predicting the onset of cALD, as well as initiating a more timely lifesaving therapy.
  
  
  
  To identify variations in the levels of antioxidant capacity and SOD activity between ALD phenotypes in patients with cALD or adrenomyeloneuropathy (AMN), heterozygote female carriers, and healthy controls and, in addition, correlate antioxidant levels with clinical outcome scores to determine a possible predictive value.
  
  
  
  Samples of monocytes and blood plasma were prospectively collected from healthy controls, heterozygote female carriers, and patients with AMN or cALD. We are counting each patient as 1 sample in our study. Because adrenoleukodystrophy is an X-linked disease, the affected group populations of cALD and AMN are all male. The heterozygote carriers are all female. The samples were assayed for total antioxidant capacity and SOD activity. The data were collected in an academic hospital setting. Eligibility criteria included patients who received a diagnosis of ALD and heterozygote female carriers, both of which groups were compared with age-matched controls. The prospective samples (n = 30) were collected between January 2015 to January 2016, and existing samples were collected from tissue storage banks at the Kennedy Krieger Institute (n = 30). The analyses were performed during the first 3 months of 2016.
  
  
  
  Commercially available total antioxidant capacity and SOD assays were performed on samples of monocytes and blood plasma and correlated with magnetic resonance imaging severity score.
  
  
  
  A reduction in antioxidant capacity was shown between the healthy controls (0.225 mmol trolox equivalent) and heterozygote carriers (0.181 mmol trolox equivalent), and significant reductions were seen between healthy controls and patients with AMN (0.102 mmol trolox equivalent; P < .01), as well as healthy controls and patients with cALD (0.042 mmol trolox equivalent; P < .01). Superoxide dismutase activity in human blood plasma mirrored these reductions between prospectively collected samples from healthy controls (2.66 units/mg protein) and samples from heterozygote female carriers (1.91 units/mg protein), patients with AMN (1.39 units/mg protein; P = .01), and patients with cALD (0.8 units/mg protein; P < .01). Further analysis of SOD activity in biobank samples showed significant reductions between patients with AMN (0.89 units/mg protein) and patients with cALD (0.18 units/mg protein) (P = .03). Plasma SOD levels from patients with cALD demonstrated an inverse correlation to brain magnetic resonance imaging severity score (R2 = 0.75, P < .002). Longitudinal plasma SOD samples from the same patients (n = 4) showed decreased activity prior to and at the time of cerebral diagnosis over a period of 13 to 42 months (mean period, 24 months).
  
  
  
  Plasma SOD may serve as a potential biomarker for cerebral disease in ALD following future prospective studies.
authors.affiliation: Moser Center for Leukodystrophies, Kennedy Krieger Institute, Departments of Neurology and Pediatrics, Johns Hopkins Medical Institutions, Baltimore, Maryland.
authors.forename: Bela R
authors.initials: BR
authors.lastname: Turk
authors.affiliation: Moser Center for Leukodystrophies, Kennedy Krieger Institute, Departments of Neurology and Pediatrics, Johns Hopkins Medical Institutions, Baltimore, Maryland.
authors.forename: Benjamin E
authors.initials: BE
authors.lastname: Theisen
authors.affiliation: Moser Center for Leukodystrophies, Kennedy Krieger Institute, Departments of Neurology and Pediatrics, Johns Hopkins Medical Institutions, Baltimore, Maryland.
authors.forename: Christina L
authors.initials: CL
authors.lastname: Nemeth
authors.affiliation: Moser Center for Leukodystrophies, Kennedy Krieger Institute, Departments of Neurology and Pediatrics, Johns Hopkins Medical Institutions, Baltimore, Maryland.
authors.forename: Joel S
authors.initials: JS
authors.lastname: Marx
authors.affiliation: Moser Center for Leukodystrophies, Kennedy Krieger Institute, Departments of Neurology and Pediatrics, Johns Hopkins Medical Institutions, Baltimore, Maryland.
authors.forename: Xiaohai
authors.initials: X
authors.lastname: Shi
authors.affiliation: Moser Center for Leukodystrophies, Kennedy Krieger Institute, Departments of Neurology and Pediatrics, Johns Hopkins Medical Institutions, Baltimore, Maryland.
authors.forename: Melissa
authors.initials: M
authors.lastname: Rosen
authors.affiliation: Moser Center for Leukodystrophies, Kennedy Krieger Institute, Departments of Neurology and Pediatrics, Johns Hopkins Medical Institutions, Baltimore, Maryland.
authors.forename: Richard O
authors.initials: RO
authors.lastname: Jones
authors.affiliation: Moser Center for Leukodystrophies, Kennedy Krieger Institute, Departments of Neurology and Pediatrics, Johns Hopkins Medical Institutions, Baltimore, Maryland.
authors.forename: Ann B
authors.initials: AB
authors.lastname: Moser
authors.affiliation: Moser Center for Leukodystrophies, Kennedy Krieger Institute, Departments of Neurology and Pediatrics, Johns Hopkins Medical Institutions, Baltimore, Maryland.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Watkins
authors.affiliation: Department of Neurology, University of Minnesota, Minneapolis.
authors.forename: Gerald V
authors.initials: GV
authors.lastname: Raymond
authors.affiliation: Moser Center for Leukodystrophies, Kennedy Krieger Institute, Departments of Neurology and Pediatrics, Johns Hopkins Medical Institutions, Baltimore, Maryland.
authors.forename: Carol
authors.initials: C
authors.lastname: Tiffany
authors.affiliation: Moser Center for Leukodystrophies, Kennedy Krieger Institute, Departments of Neurology and Pediatrics, Johns Hopkins Medical Institutions, Baltimore, Maryland.
authors.forename: Ali
authors.initials: A
authors.lastname: Fatemi
mesh_terms: D000293:Adolescent; D000326:Adrenoleukodystrophy / Q000097:blood* / Q000000981:diagnostic imaging / Q000235:genetics; D000975:Antioxidants / Q000378:metabolism*; D015415:Biomarkers / Q000097:blood; D002648:Child; D002675:Child, Preschool; D005260:Female; D006579:Heterozygote; D006801:Humans; D007223:Infant; D008297:Male; D009000:Monocytes / Q000378:metabolism*; D010641:Phenotype; D011446:Prospective Studies; D012189:Retrospective Studies; D013053:Spectrophotometry; D013482:Superoxide Dismutase / Q000378:metabolism*; D014015:Tissue Banks
chemical_list: D000975:Antioxidants; D015415:Biomarkers; D013482:Superoxide Dismutase