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
A method for detecting citrullinated brain injury biomarker proteins in a sample from a patient, the method comprising:
- detecting in a patient sample citrullinated arginine residues in citrullinated brain injury biomarker protein neurogranin (NRGN) and in one or more citrullinated brain injury biomarker proteins selected from the group consisting of tubulin beta-4B chain, tubulin alpha-1B chain, CNPase, PPIA, Septin-7, Elongation factor1-alpha2, TPPP, TPPP3, Ermin Isoform 2, NDRG2Isoform 2, astrotactin 1 (ASTN1), brain angiogenesis inhibitor 3 (BAI3), carnosine dipeptidase 1 (CNDP1), ERMIN, glial fibrillary acidic protein (GFAP), glutamate receptor metabotropic 3 (GRM3), kelch-like protein 32 (KLH32), melanoma antigen family E,2 (MAGE2), myelin basic protein (MBP), neuregulin 3 (NRG3), oligodendrocyte myelin glycoprotein (OMG), solute carrier family 39 (zinc transporter), reticulon 1 (RTN1), MT3, and peptidylarginine deiminase (types 1-4 and 6) (PAD) by contacting the citrullinated arginine residues in the citrullinated brain injury biomarker proteins with an antibody that binds to said citrullinated arginine residues and detecting binding of the antibody to the residues or by detecting the citrullinated arginine residues using mass spectrometry, thereby detecting citrullinated brain injury biomarker proteins in the patient's sample.
A method for detecting autoantibodies against a citrullinated brain injury biomarker protein in a sample from a subject, the method comprising the steps of:
- (a) contacting a biological sample obtained from the subject with citrullinated brain injury biomarker protein neurogranin (NRGN) and one or more citrullinated brain injury biomarker proteins selected from the group consisting of tubulin beta-4B chain, tubulin alpha-1B chain, CNPase, PPIA, Septin-7, Elongation factorl-alpha2, TPPP, TPPP3, Ermin Isoform 2, NDRG2 Isoform 2, astrotactin 1 (ASTN1), brain angiogenesis inhibitor 3 (BAI3);
- carnosine dipeptidase 1 (CNDP1);
- ERMIN;
- glial fibrillary acidic protein (GFAP);
- glutamate receptor metabotropic 3 (GRM3);
- kelch-like protein 32 (KLH32);
- melanoma antigen family E,2(MAGE2);
- myelin basic protein (MBP);
- neuregulin 3 (NRG3);
- oligodendrocyte myelin glycoprotein (OMG);
- solute carrier family 39 (zinc transporter);
- reticulon 1 (RTN1);
- MT3, and peptidylarginine deiminase (types 1-4 and 6) (PAD));
- and
- (b) detecting the binding of the citrullinated brain injury biomarker proteins to autoantibodies in the sample which are specific for the citrullinated brain injury biomarker proteins, wherein the detection of binding is indicative of the presence of citrullinated brain injury biomarker protein autoantibodies.
Dependencies are inferred from the claim text.