Diagnosis of liver pathology through assessment of protein glycosylation
Methods for diagnosing pathology of the liver in a subject suspected of having such pathology are disclosed. The methods comprise quantifiably detecting lectin binding on proteins in biological fluids, and comparing the detected lectin binding with reference values for the binding of lectin of such proteins in healthy or disease states.
1. A method for assessing the pathological status of a liver in a subject suspected of having a liver pathology comprising:
obtaining biological fluid from the subject;
capturing a protein in the biological fluid using a deglycosylated capture reagent comprising an antibody that is specific to said protein,
wherein said protein is selected from
GP73, haptoglobin, hepatitis B viral particle, alpha-1-antichymotrypsin, alpha-1-antichymotrypsin His-Pro-less, Ceruloplasmin, alpha-2-HSglycoprotein, Fibrinogen gamma chain precursor, APO-D, Kininogen, Histidine rich glycoprotein, complement factor 1 precursor, complement factor I heavy chain, complement factor I light chain, Complement C1s, Complement factor B precursor, complement factor B Ba fragment, Complement factor B Bb fragment, Complement C3 precursor, Complement C3 beta chain, C3a anaphylatoxin, Complement C3b alpha′ chain, Complement C3c fragment, Complement C3dg fragment, Complement C3g fragment, Complement C3d fragment, Complement C3f fragment, Complement C5, Complement C5 beta chain, Complement C5 alpha chain, C5a anaphylatoxin, Complement C5 alpha′ chain, Complement C7, alpha-1 B glycoprotein, B-2-glycoprotein, Vitamin D-binding protein, Inter-alpha-trypsin inhibitor heavy chain H2, Angiotensinogen precursor, Angiotensin-1, Angiotensin-2, Angiotensin-3, GARP protein, Clusterin (Apo J), Integrin alpha-8 precursor glycoprotein, Integrin alpha-8 heavy chain, Integrin alpha-8 light chain, hepatitis C viral particle, and Leucine-rich repeat-containing protein 32 precursor,
contacting said biological fluid with a core fucose-binding lectin and allowing said lectin to bind to the captured protein in said biological fluid,
wherein the binding of said core fucose-binding lectin to said protein is determinative as to the presence of core fucose on said protein;
quantifiably detecting bound lectin in the biological fluid to obtain a detected core fucosylation value; and
comparing the detected core fucosylation value with a reference value for core fucosylation on said protein in a comparable biological fluid of subjects without said liver pathology, said detected core fucosylation value relative to the reference value being indicative of the presence or absence of said liver pathology, wherein a detected core fucosylation value that deviates from said reference value to a statistically significant degree is indicative of the presence of said liver pathology,
or
comparing the detected core fucosylation value with a reference value for core fucosylation on said protein in a comparable biological fluid of subjects in which said liver pathology is known to be present, said detected core fucosylation value relative to the reference value being indicative of the presence or absence of said liver pathology, wherein a detected core fucosylation value that deviates from said reference value to a statistically significant degree is indicative of the absence of said liver pathology.
2. The method according to claim 1 wherein said liver pathology is cirrhosis.
3. The method according to claim 1 wherein said liver pathology is fibrosis.
4. The method according to claim 1 wherein said liver pathology is hepatocellular carcinoma.
5. The method according to claim 1 wherein said liver pathology is hepatitis.
6. The method of claim 1 wherein the biological fluid is whole blood, serum, urine, saliva, tears, or mucous.
7. The method of claim 1 , wherein the lectin is coupled to a detectable moiety.
8. The method of claim 1 , wherein the reagent for capturing the protein is immobilized on a solid support.