Citrullinated brain and neurological proteins as biomarkers of brain injury or neurodegeneration
AssigneeThe Johns Hopkins University
InventorsJENNIFER E. VAN EYK, ALLEN DALE EVERETT, ZHICHENG JIN
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Abstract
The present invention relates to the field of biomarkers. More specifically, the present invention relates to biomarkers useful in diagnosing brain injury or neurodegeneration. In one embodiment, a method for diagnosing brain injury in a patient comprises the steps of (a) obtaining a sample from the patient; (b) determining the ratio of citrullinated to unmodified arginine residues at one or more arginine residues of one or more brain injury biomarker proteins; and (c) correlating the ratio to a patient having brain injury or to a patient not having brain injury, thereby providing the diagnosis.
Claims20
(canceled)
A method for detecting post-translational modification of one or more brain injury biomarker proteins in a sample from a subject having or suspected of having brain injury, the method comprising:
- (a) subjecting a biological sample obtained from a subject having or suspected of having brain injury to a detection method selected from mass spectrometry, immunoassay, electrochemical luminescent assay, electrochemical voltametry, electrochemical amperometry, atomic force microscopy, radio frequency multipolar resonance spectroscopy, confocal microscopy, non-confocal microscopy, fluorescence optical detection, luminescence optical detection, chemiluminescence optical detection, absorbance optical detection, reflectance optical detection, transmittance optical detection, birefringence optical detection, refractive index detection, surface plasmon resonance, ellipsometry, resonant mirror detection, grating coupler waveguide detection, or interferometry, to detect one or more post-translationally modified brain injury biomarker proteins in the sample, wherein the one or more brain injury biomarker proteins is selected from the group consisting of glial fibrillary acidic protein (GFAP), myelin basic protein (MBP), neurogranin (NRGN), and a combination thereof, and the post-translational modification comprises citrullination, oxidation, methylation, phosphorylation, cysteinylation s-nitrosation, s-glutathyolation, or a combination thereof, and
- (b) detecting in the sample one or more post-translationally modified brain injury biomarker proteins or specific amino acid residues on the post-translationally modified brain injury biomarker proteins relative to a control sample, thereby detecting post-translational modification of the one or more brain injury biomarker proteins in the sample.
A method for detecting autoantibodies directed against a post-translationally modified brain injury biomarker protein in a subject, the method comprising:
- (a) contacting a biological sample obtained from the subject with a post-translationally modified brain injury biomarker protein selected from the group consisting of glial fibrillary acidic protein (GFAP), myelin basic protein (MBP), neurogranin (NRGN), and a combination thereof, wherein the post-translational modification of the biomarker protein comprises citrullination, oxidation, methylation, phosphorylation, cysteinylation s-nitrosation, s-glutathyolation, or a combination thereof;
- and
- (b) detecting specific binding or binding complexes between the post-translationally modified brain injury biomarker protein and autoantibodies in the sample, thereby detecting autoantibodies directed against the post-translationally modified brain injury biomarker protein in the subject. Notice to File Missing Parts of Nonprovisional Application (Filing Date Granted)
A method of treating a patient having or suspected of having a brain injury, the method comprising:
- a. quantifying the ratio of one or more citrullinated biomarker peptides to one or more corresponding unmodified biomarker peptides in a sample collected from a patient having or suspected of having brain injury;
- b. quantifying the ratio of one or more post-translationally modified biomarker peptides to one or more corresponding unmodified biomarker peptides in the sample collected from the patient of step a;
- c. comparing the one or more citrullinated:
- unmodified biomarker peptide ratios to the one or more post-translationally modified:
- unmodified biomarker peptide ratios;
- wherein a higher ratio of citrullinated:
- unmodified biomarker peptides and/or a higher ratio of post-translationally modified:
- unmodified biomarker peptides trend toward the ratios of a brain injury control;
- and
- d. administering a brain injury therapy to the patient when the compared ratios in step c) trend toward brain injury.
Dependencies are inferred from the claim text.