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
Life of this patent
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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.
Claims60
A method for diagnosing brain injury in a patient comprising 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.
A method for diagnosing brain injury in a patient comprising the steps of:
- a. determining the ratio of one or more citrullinated peptides to the corresponding unmodified peptides in a sample collected from the patient using mass spectrometry;
- and
- b. correlating the ratio to a patient having brain injury or to a patient not having brain injury, thereby providing the diagnosis.
A method for diagnosing brain injury in a patient comprising the steps of:
- a. determining the ratio of one or more citrullinated peptides to the corresponding unmodified peptides in a sample collected from the patient using mass spectrometry;
- and
- b. comparing the ratio with predefined ratios of the same peptides that correlate to a patient having brain injury and predefined ratios of the same peptides that correlate to a patient not having brain injury, wherein a correlation to one of the predefined ratios provides the diagnosis.
A method for diagnosing brain injury in a patient comprising the steps of:
- a. determining the ratio of one or more post-translationally modified peptides to the corresponding unmodified peptides in a sample collected from the patient using MRM-MS;
- and
- b. correlating the ratio to a patient having brain injury or to a patient not having brain injury, thereby providing the diagnosis.
A method for diagnosing brain injury in a patient comprising the steps of:
- a. determining the ratio of one or more post-translationally modified peptides to the corresponding unmodified peptides in a sample collected from the patient using MRM-MS;
- and
- b. comparing the one or more ratios with predefined ratios of the same post-translationally modified/unmodified peptides that correlate to a patient having brain injury and predefined ratios of the same post-translationally modified/unmodified peptides that correlate to a patient not having brain injury, wherein a correlation to one of the predefined ratios provides the diagnosis.
A method for diagnosing brain injury in a patient comprising the steps of:
- a. determining the ratio of one or more citrullinated peptides to the corresponding unmodified peptides in a sample collected from the patient using mass spectrometry;
- b. determining the ratio of one or more post-translationally modified peptides to the corresponding unmodified peptides in the same sample collected from the patient using MRM-MS;
- c. comparing the one or more citrullinated:unmodified peptide ratios to one or more post-translationally modified:unmodified peptide ratios;
- and
- d. correlating the compared ratios to a patient having brain injury or to a patient not having brain injury, thereby providing the diagnosis.
A method for diagnosing brain injury in a patient comprising the steps of:
- a. determining the degree of citrullination of one or more arginine sites of one or more of NRGN, PAD, MBP GFAP, isoforms thereof, post-translationally modified forms thereof, or combinations of any of the foregoing;
- and
- b. correlating the degree of citrullination to a patient having brain injury or to a patient not having brain injury, thereby providing the diagnosis.
A method for diagnosing brain injury in a patient comprising the steps of:
- a. measuring the level of one or more citrullinated brain injury biomarker proteins in a sample collected from the patient;
- and
- b. comparing the level of the one or more biomarkers with predefined levels of the same biomarkers that correlate to a patient having brain injury and predefined levels of the same biomarkers that correlate to a patient not having brain injury, wherein a correlation to one of the predefined levels provides the diagnosis.
A method for diagnosing brain injury in a patient comprising the steps of:
- a. collecting a sample from the patient;
- b. measuring the levels of a panel of citrullinated brain injury biomarker proteins in the sample collected from the patient using mass spectrometry, wherein the panel of biomarkers comprises NRGN, MBP, GFAP, PAD, isoforms thereof, post-translationally modified forms thereof, or combinations of any of the foregoing;
- and
- c. comparing the levels of the panel of biomarkers with predefined levels of the same panel of biomarkers that correlate to a patient having brain injury and predefined levels of the same panel of biomarkers that correlate to a patient not having brain injury, wherein a correlation to one of the predefined levels provides the diagnosis.
A method for determining brain injury status in a patient comprising the steps of:
- a. collecting a sample from the patient;
- b. measuring the levels of a panel of citrullinated brain injury biomarker proteins in the sample collected from the patient using SRM-MS, wherein the panel of biomarkers comprises NRGN, MBP, GFAP, PAD, isoforms thereof, post-translationally modified forms thereof, or combinations of any of the foregoing;
- and
- c. comparing the levels of the panel of biomarkers with predefined levels of the same panel of biomarkers that correlate to one or more brain injury statuses selected from the group consisting of having brain injury, not having brain injury, progressing brain injury, and regressing brain injury, wherein a correlation to one of the predefined levels determines the brain injury status of the patient.
A diagnostic kit for diagnosing brain injury in a patient comprising:
- a. a substrate for collecting a biological sample from the patient;
- and
- b. means for measuring the levels of one or more human citrullinated brain injury biomarker proteins selected from the group consisting of NRGN, MBP, GFAP, PAD, isoforms thereof, post-translationally modified forms thereof, or combinations of any of the foregoing.
A method for diagnosing brain injury in a subject comprising the steps of:
- a. collecting a sample from the subject;
- b. detecting the presence of autoantibodies to citrullinated brain injury biomarker peptides in the sample collected from the subject;
- and
- c. correlating the amount of autoantibodies to citrullinated brain injury biomarker peptides to a patient having brain injury or to a patient not having brain injury, thereby providing the diagnosis.
A method for assessing efficacy of a brain injury treatment regimen in a subject comprising:
- a. establishing a baseline level of autoantibodies to cit-NRGN, cit-MBP, and cit-GFAP in a subject prior to brain injury treatment regimen;
- b. monitoring the levels of autoantibodies to cit-NRGN, cit-MBP, and cit-GFAP using a cit-NRGN, cit-MBP, and cit-GFAP peptide at least at one point after initiation of the brain injury treatment regimen;
- and
- c. comparing the observed level of autoantibodies to cit-NRGN, cit-MBP, and cit-GFAP to the baseline level of autoantibodies to cit-NRGN, cit-MBP, and cit-GFAP, wherein a decrease in the level of autoantibodies is indicative of the efficacy of the brain injury treatment regimen.
A method for qualifying brain injury status in a subject comprising
- a. measuring the level of autoantibodies to cit-NRGN, cit-MBP, and cit-GFAP in a biological sample from the subject;
- and
- b. correlating the measurement with brain injury status.
Dependencies are inferred from the claim text.