Articles for diagnosis of liver fibrosis
AssigneeThe Government of the United States, as represented by the Secretary of the Army
InventorsMohamed Diwan M. ABDULHAMEED, Gregory J. TAWA, Danielle L. IPPOLITO, John A. LEWIS, Anders WALLQVIST, Jonathan D. STALLINGS, Matthew G. PERMENTER
Life of this patent
Estimating the term…
Abstract
Disclosed are methods and articles (e.g., gene arrays or antibodies) for determining the progression or regression of liver fibrosis, for the diagnosis of liver disease, and for screening compounds for hepatotoxicity and efficacy against liver fibrosis. Related therapeutic methods also are disclosed.
Claims43
An in vitro method for detecting early stage liver disease in a mammalian subject, comprising:
- assaying a biological sample from a subject for differential expression of at least twenty-five genes selected from the group consisting of Lcn2;
- Gpnmb;
- Lgals3;
- S100A11;
- Anxa2;
- Lbp;
- Col1a1;
- Cxcl16;
- Timp1;
- Plat;
- RT1-DMa;
- CD9;
- Lgals1;
- Tagin2;
- RT1-DMd;
- Capg;
- Pkm2;
- Ccl2;
- Serpine1;
- Cyba;
- Fam105a;
- Cxcl1;
- Vim;
- C1qb;
- Pcolce;
- Fxyd5;
- Arpc1b;
- S100A6;
- Plau;
- It gal;
- Plod2;
- Ctgf Col1a2;
- Igfbp2;
- Lox;
- Fam102b;
- CD53;
- Itgb2;
- Lamc2;
- CP;
- Slc25a24;
- Fbn1;
- Col4al;
- Sod2;
- Cyp2cl1;
- Igfbp3;
- Cxcl12;
- Angptl3;
- Igfals;
- Tgfbi;
- Vin;
- Vh1, and orthologs thereof corresponding to the subject, and orthologs thereof corresponding to the subject, wherein the differential expression of the at least twenty-five genes is indicative of early stage liver disease in the subject.
A method for detecting progression or regression of liver fibrosis in a mammalian subject, comprising detecting differential expression of at least twenty-five genes selected from the group consisting of:
- Lcn2;
- Gpnmb;
- Lgals3;
- S100A11;
- Anxa2;
- Lbp;
- Col1a1;
- Cxcl16;
- Timp1;
- Plat;
- RT1-DMa;
- CD9;
- Lgals1;
- Tagin2;
- RT1-Da;
- Capg;
- Pkm2;
- Ccl2;
- Serpine1;
- Cyba;
- Fam105a;
- Cxcl1;
- Vim;
- C1qb;
- Pcolce;
- Fxyd5;
- Arpc1b;
- S100A6;
- Plau;
- Itgal;
- Plod2;
- Ctgf;
- Col1a2;
- Igfbp2;
- Lox;
- Fam102b;
- CD53;
- Itgb2;
- Lamc2;
- CP;
- Slc25a24;
- Fbn1;
- Col4a1;
- Sod2;
- Cyp2cl1;
- Igfbp3;
- Cxcl12;
- Angptl3;
- Igfals;
- Tgfbi;
- Vtn;
- Vh1, and orthologs thereof corresponding to the subject, in a biological sample from the subject.
A method of identifying a compound that increases or decreases the differential expression of at least one gene associated with hepatotoxicity, comprising
- (i) providing a cell expressing at least one gene selected from the group consisting of Lcn2;
- Gpnmb;
- Lgals3;
- S100A11:
- Anxa2;
- Lbp;
- Col1a1;
- Cxc116;
- Timp1;
- Plat;
- RT1-DMa;
- CD9;
- Lgals1;
- Tagin2;
- RT1-Da;
- Capg;
- Pkrn2;
- Ccl2;
- Serpine1;
- Cyba;
- Fam105a;
- Cxcl1;
- Vim;
- C1qb;
- Pcolce;
- Fxyd5;
- Arpc1b;
- S100A6;
- Plau;
- Itgal;
- Plod2;
- Ctgf;
- Col1a2;
- Igfbp2;
- Lox;
- Fam102b;
- CD53;
- Itgb2;
- Lamc2;
- CP, Slc25a24;
- Fbn1;
- Col4a1;
- Sod2;
- Cyp2c11;
- Igfbp3;
- Cxcl12;
- Angptl3;
- Igfals;
- Tgfbi;
- Vtn;
- Vh1, Cyp2c11;
- Igfbp3;
- Cxcl12;
- Angptl3;
- Igfals;
- Tgfbi;
- Vtn;
- Vh1, and mammalian orthologs thereof;
- (ii) contacting the cell with a test compound;
- and
- (iii) determining whether the differential expression of the at least one gene is increased or decreased in the presence of the test compound.
An array comprising at least twenty-five target oligonucleotides immobilized on a substrate, wherein each target oligonucleotide comprises a sequence that is specifically hybridizable to mRNA, cDNA or miRNA corresponding to one of at least twenty-five separate genes selected from the group consisting of Lcn2;
- Gpnmb;
- Lgals3;
- S100A11;
- Anxa2;
- Lbp;
- Col1a1;
- Cxcl16;
- Timp1;
- Plat;
- RT1-DMa;
- CD9;
- Lgals1;
- Tagin2;
- RT1-Da;
- Capg;
- Pkm2;
- Ccl2;
- Serpine1;
- Cyba;
- Fam105a;
- Cxcl1;
- Vim;
- C1qb;
- Pcolce;
- Fxyd5;
- Arpc1b;
- S100A6;
- Plau;
- Itgal;
- Plod2;
- Ctgf, Col1a2;
- Igfbp2;
- Lox;
- Fam102b;
- CD53;
- Itgb2;
- Lamc2;
- CP;
- Slc25a24;
- Fbn1;
- Col4al;
- Sod2;
- Cyp2c11;
- Igfbp3;
- Cxcl12;
- Angptl3;
- Igfals;
- Tgfbi;
- Vtn;
- Vh1, and mammalian orthologs thereof, such that the array comprises at least one target oligonucleotide specifically hybridizable to each of the at least twenty-five genes.
A kit for the diagnosis of liver disease, comprising at least twenty-five detectably labelled oligonucleotides, wherein each oligonucleotides comprises a sequence that is specifically hybridizable to mRNA, cDNA or miRNA corresponding to one of at least twenty-five separate genes selected from the group consisting of Lcn2;
- Gpnmb;
- Lgals3;
- S100A11;
- Anxa2;
- Lbp;
- Col1a1;
- Cxcl16;
- Timp1;
- Plat;
- RT1-DMa;
- CD9;
- Lgals1;
- Tagin2;
- RT1-DMd;
- Capg;
- Pkm2;
- Ccl2;
- Serpine1;
- Cyba;
- Fam105a;
- Cxcl1;
- Vim;
- C1qb;
- Pcolce;
- Fxyd5;
- Arpc1b;
- S100A6;
- Plau;
- Itgal;
- Plod2;
- Ctgf;
- Col1a2;
- Igfbp2;
- Lox;
- Fam102b;
- CD53;
- Itgb2;
- Lamc2;
- CP;
- Slc25a24;
- Fbn1;
- Col4a1;
- Sod2;
- Cyp2cl1;
- Igfbp3;
- Cxcl12;
- Angptl3;
- Igfals;
- Tgfbi;
- Vtn;
- Vh1, and mammalian orthologs thereof, such that the kit comprises at least one detectably labelled oligonucleotide specifically hybridizable to mRNA, cDNA or miRNA corresponding to each of the at least twenty-five genes.
A kit for the diagnosis of liver disease, comprising at least twenty-five antibodies, or antigen-binding fragments thereof, wherein each antibody or fragment thereof is capable of specifically binding to one of at least twenty-five separate proteins encoded by genes selected from the group consisting of Lcn2;
- Gpnmb;
- Lgals3;
- S100A11;
- Anxa2;
- Lbp;
- Collal;
- Cxcl16;
- Timp1;
- Plat;
- RT1-DMa;
- CD9;
- Lgals1;
- Tagin2;
- RT1-Da;
- Capg;
- Pkm2;
- Ccl2;
- Serpine1;
- Cyba;
- Fam105a;
- Cxcl1;
- Vim;
- C1qb;
- Pcolce;
- Fxyd5;
- Arpc1b;
- S100A6;
- Plau;
- Itgal;
- Plod2;
- Ctgf;
- Col1a2;
- Igfbp2;
- Lox;
- Fam102b;
- CD53;
- Itgb2;
- Lamc2;
- CP;
- Slc25a24;
- Fbn1;
- Col4a1;
- Sod2;
- Cyp2c11;
- Igfbp3;
- Cxcl12;
- Angptl3;
- Igfals;
- Tgfbi;
- Vtn;
- Vh1, and mammalian orthologs thereof, such that the kit comprises at least one antibody or antigen-binding fragment thereof that specifically binds to each of the at least twenty-five separate proteins.
A method of detecting expression of at least one gene in a biological sample from a mammalian subject suspected of having or determined to be at risk of developing liver fibrosis or liver disease, comprising quantifying levels of mRNA, cDNA or miRNA corresponding to at least one gene selected from the group consisting of Dsc2;
- Fam102b;
- Fam105a;
- Gpnmb;
- Pcolce;
- RT1-Da;
- RT1-DMA;
- Slc25a24;
- Tagin2;
- Arpc1b;
- Angptl3;
- Anxa2;
- Cd53;
- Cd9;
- Cp;
- C1qb;
- Fxyd5;
- Igfbp2;
- Igfbp3;
- Igfals;
- Lamac2;
- Lgals1;
- Lgals3;
- Lrp1;
- Plod2;
- Pkm;
- S100a11;
- S00a6;
- Serpine1;
- Serping′;
- Vim, and orthologs thereof corresponding to the subject.
Dependencies are inferred from the claim text.