Clinical diagnosis of hepatic fibrosis using a novel panel of human serum protein biomarkers
First Claim
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1. A method of diagnosing hepatic fibrosis comprising:
- a) obtaining a biological sample from a subject in need thereof;
b) detecting in said biological sample i) a level of apolipoprotein L1 (ApoL1) and ii) a level of at least one HF-ASSOCIATED polypeptide selected from the group consisting of;
inter-α
-trypsin inhibitor heavy chain H4 fragments, α
1 antichymotrypsin, prealbumin, isoforms of CD5 antigen like protein (CD5L), β
2 glycoprotein I (β
2GPI), thioester cleaved α
2 macroglobulin (a2M) and immunoglobulin components, α
1, α
2 and β
chains of haptoglobin, complement components C3 and factor H-related protein 1, ApoE, clusterin, and angiotensinogen; and
c) diagnosing hepatic fibrosis in said subject by comparing said level of apolipoprotein L1 and said level of the at least one HF-ASSOCIATED polypeptide detected in said biological sample to a control level of apolipoprotein L1 and a control level of said HP-ASSOCIATED polypeptide, respectively,wherein a decrease in the level of, or absence of inter-α
-trypsin inhibitor heavy chain H4 fragments, prealbumin, complement components C3 and factor H-related protein 1, α
1 antichymotrypsin, α
1, α
2 and β
chains of haptoglobin, and ApoL1, corresponds to hepatic fibrosis,wherein an increase in the level of, or presence of thioester cleaved a2M and immunoglobulin components, β
2GPI, and isoforms of CD5 antigen like protein, corresponds to hepatic fibrosis.
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Abstract
The inventors have proposed a novel panel of human serum protein biomarkers for diagnosing hepatic fibrosis and cirrhosis. Presently there is no reliable non-invasive way of assessing liver fibrosis. A 2D-PAGE based proteomics study was used to identify potential fibrosis biomarkers. Serum from patients with varying degrees of hepatic scarring induced by infection with the hepatitis C virus (HCV) was analyzed. Several proteins associated with liver scarring and/or viral infection were identified. These proteins include the inter-α-trypsin inhibitor heavy chain H4 fragments, complement factor H-related protein 1, CD5L, Apo L1, and β2GPI. Increased and decreased thiolester cleavage of a2M and Complement C3, respectively, was also detected. The concentrations of these novel biomarkers can be determined using an immunoassay where the concentrations would reflect the extent of fibrosis. A fibrosis scoring scale for each of the novel biomarkers is proposed. The additive result from the scores of all the novel biomarkers would give a more reliable indication of the degree of fibrosis rather than examining individual biomarkers.
34 Citations
22 Claims
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1. A method of diagnosing hepatic fibrosis comprising:
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a) obtaining a biological sample from a subject in need thereof; b) detecting in said biological sample i) a level of apolipoprotein L1 (ApoL1) and ii) a level of at least one HF-ASSOCIATED polypeptide selected from the group consisting of;
inter-α
-trypsin inhibitor heavy chain H4 fragments, α
1 antichymotrypsin, prealbumin, isoforms of CD5 antigen like protein (CD5L), β
2 glycoprotein I (β
2GPI), thioester cleaved α
2 macroglobulin (a2M) and immunoglobulin components, α
1, α
2 and β
chains of haptoglobin, complement components C3 and factor H-related protein 1, ApoE, clusterin, and angiotensinogen; andc) diagnosing hepatic fibrosis in said subject by comparing said level of apolipoprotein L1 and said level of the at least one HF-ASSOCIATED polypeptide detected in said biological sample to a control level of apolipoprotein L1 and a control level of said HP-ASSOCIATED polypeptide, respectively, wherein a decrease in the level of, or absence of inter-α
-trypsin inhibitor heavy chain H4 fragments, prealbumin, complement components C3 and factor H-related protein 1, α
1 antichymotrypsin, α
1, α
2 and β
chains of haptoglobin, and ApoL1, corresponds to hepatic fibrosis,wherein an increase in the level of, or presence of thioester cleaved a2M and immunoglobulin components, β
2GPI, and isoforms of CD5 antigen like protein, corresponds to hepatic fibrosis. - View Dependent Claims (2, 4, 5, 6, 7, 8, 9, 10, 11, 13, 15, 17, 18, 19)
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3. A method for scaling the severity of hepatic fibrosis comprising:
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a) obtaining a biological sample from a subject in need thereof; b) detecting in said biological sample i) a concentration of apolipoprotein L1 (ApoL1) and ii) a concentration of at least one HF-ASSOCIATED polypeptide selected from the group consisting of;
inter-α
-trypsin inhibitor heavy chain H4 fragments, α
1 antichymotrypsin, prealbumin, isoforms of CD5 antigen like protein (CD5L), β
2 glycoprotein (β
2GPI), thioester cleaved α
2 macroglobulin (a2M) and immunoglobulin components, α
1, α
2 and β
chains of haptoglobin, complement components C3 and factor H-related protein 1, ApoE, clusterin, and angiotensinogenc) comparing said concentration of apoliprotein L1 and said concentration of the at least one HF-ASSOCIATED polypeptide detected in said biological sample to a predetermined concentration of apolipoprotein L1 and a predetermined concentration of said at least one HF-ASSOCIATED polypeptide, respectively, in a population of patients ranging from no fibrosis to cirrhosis; and d) scaling the severity of hepatic fibrosis by determining concentration ranges of apolipoprotein L1 and the at least one HF-ASSOCIATED polypeptide across no fibrosis, representing a score of 0, to cirrhosis, representing a score of 6, wherein a decrease in the concentration of, or absence of inter-α
-trypsin inhibitor heavy chain H4 fragments, prealbumin, complement components C3 and factor H-related protein 1, α
1 antichymotrypsin, α
1, α
2 and β
chains of haptoglobin, and ApoL1, corresponds to hepatic fibrosis;wherein an increase in the concentration of, or presence of thioester cleaved a2M and immunoglobulin components, β
2GPI, and isoforms of CD5 antigen like protein, corresponds to hepatic fibrosis. - View Dependent Claims (12, 14, 16, 20, 21, 22)
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Specification
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Current AssigneeUniversity of Oxford
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Original AssigneeChancellor Masters & Scholars of The University of Cambridge (University of Cambridge)
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InventorsGangadharan, Bevin, Zitzmann, Nicole, Dwek, Raymond A.
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Primary Examiner(s)Counts, Gary W
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Application NumberUS11/851,619Publication NumberTime in Patent Office2,783 DaysField of SearchNoneUS Class Current435/7.92CPC Class CodesG01N 2333/775 ApolipopeptidesG01N 2800/085 Liver diseases, e.g. portal...G01N 33/576 for hepatitisG01N 33/5767 non-A, non-B hepatitisG01N 33/6893 related to diseases not pro...Y10S 436/811 Test for named disease, bod...
