Multi-protein biomarker assay for brain injury detection and outcome
The present invention relates to the field of brain injuries. More specifically, the present invention provides methods and compositions useful in the diagnosis/prognosis/assessment of brain injuries. In a specific embodiment, a method for identifying which patients with traumatic brain injury (TBI) require a head computerized tomography (CT) scan for diagnosing acute intracranial pathology comprises the steps of (a) obtaining or collecting a sample from the patient; (b) measuring the levels of one or more biomarkers in the blood sample obtained from the patient, wherein the biomarkers comprise glial fibrillary acidic protein (GFAP), S100B, metallothionein 3 (MT3), neuron specific enolase (NSE) and intracellular adhesion molecule 5 (ICAM5); and (c) identifying the patient as requiring or not requiring a head CT scan based on the measured levels of one or more of biomarkers comprising GFAP, S100B, MT3, NSE and ICAM5.
1. A method of detecting a protein biomarker in a sample obtained from a patient having or at risk of having traumatic brain injury (TBI) and/or concussion, the method comprising:
performing an assay comprising detecting a brain derived neurotrophic factor (BDNF) protein biomarker in a biological sample obtained from a patient having or at risk of having TBI and/or concussion using one or more of an immunoassay or mass spectrometry;
measuring the level of the BDNF protein biomarker in the patient sample relative to the level of the BDNF protein biomarker in one or both of a non-TBI reference or a non-concussion reference; and
when the level of the BDNF protein biomarker in the sample is not decreased relative to the reference, returning the patient to play or to work immediately.
2. The method of claim 1 , wherein the biological sample is selected from the group consisting of blood, plasma, serum, or cerebrospinal fluid (CSF).
3. The method of claim 1 , wherein the immunoassay is an enzyme linked immunosorbent assay (ELISA), a chemiluminescence-based immunoassay, or a fluorescence-based immunoassay.
4. The method of claim 1 , further comprising detecting in the patient's sample one or both of Glial Fibrillary Acidic Protein (GFAP) or S100B protein biomarkers.
5. The method of claim 4 , wherein at least one of the protein biomarkers is methylated, citrullinated, glycosylated, acetylated, or phosphorylated.
6. The method of claim 1 , wherein the patient has or is at risk of having short or long term post-concussive symptoms or disability after TBI.
7. The method of claim 1 , further comprising detecting in the patient's sample one or both of Metallothionein 3 (MT3) or Neuron Specific Enolase (NSE).
8. The method of claim 1 , further comprising detecting Neurogranin (NRGN) in the patient's sample.
9. The method of claim 1 , wherein the non-TBI reference or the non-concussion reference comprises a non-TBI control sample or a non-concussion control sample.
10. A method of managing patient treatment for traumatic brain injury (TBI) and/or concussion, the method comprising:
(a) obtaining a biological sample from a patient;
(b) detecting BDNF in the sample using a detection method selected from the group consisting of an immunoassay, mass spectroscopy, polymerase chain reaction, biochip assay, electrochemical voltametry, amperometry, atomic force microscopy, radio frequency techniques, multipolar resonance spectroscopy, microscopy, confocal microscopy, non-confocal microscopy, surface plasmon resonance, ellipsometry, resonant mirror technique, a grating coupler waveguide technique, and interferometry;
(c) measuring the level of BDNF in the sample compared to the level of BDNF in a non-brain injury reference;
(d) detecting a decreased level of BDNF in the sample compared to the reference based on step (c); wherein said decreased level of BDNF indicates that the patient has or is at risk of having TBI and/or concussion; and
(e) administering a brain injury therapy regimen to the patient when a decreased level of BDNF is detected in the patient compared to the reference, thereby managing patient treatment for TBI and/or concussion.
11. The method of claim 10 , wherein the biological sample is selected from the group consisting of blood, plasma, serum, or cerebrospinal fluid (CSF).
12. The method of claim 10 , wherein the detection assay is an immunoassay.
13. The method of claim 12 , wherein the immunoassay is an enzyme linked immunosorbent assay (ELISA), a chemiluminescence-based immunoassay, or a fluorescence-based immunoassay.
14. The method of claim 10 , further wherein the patient has or is at risk of having concussive brain injury, intracerebral hemorrhage (ICH), short or long-term post-concussive symptoms, or disability after traumatic brain injury (TBI).
15. The method of claim 10 , further comprising detecting in the patient's sample one or both of Glial Fibrillary Acidic Protein (GFAP) or S100B protein biomarkers.
16. The method of claim 10 , further comprising detecting in the patient's sample one or both of Metallothionein 3 (MT3) or Neuron Specific Enolase (NSE).
17. The method of claim 10 , further comprising detecting Neurogranin (NRGN) in the patient's sample.
18. The method of claim 10 , wherein the reference comprises a control sample or subject.