Methods and compositions for diagnosis and prognosis of appendicitis and differentiation of causes of abdominal pain
AssigneeAstute Medical, Inc.
InventorsJOSEPH ANDERBERG, JEFF GRAY, PAUL MCPHERSON, KEVIN NAKAMURA, JAMES PATRICK KAMPF, THOMAS KWAN
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Abstract
The present invention relates to methods and compositions for monitoring, diagnosis, prognosis, and determination of treatment regimens in appendicitis patients and in patients at risk for appendicitis. In particular, the invention relates to using as-says that detect one or more biomarkers as diagnostic and prognostic biomarker assays in such patients.
Claims25
A method of diagnosing appendicitis in a subject, or assigning a likelihood of a future outcome to a subject diagnosed with appendicitis, comprising:
- performing one or more assays configured to detect one or more biomarkers selected from the group consisting of 72 kDa type IV collagenase, Adiponectin, Advanced glycosylation end product-specific receptor, Alpha-2 macroglobulin, Alpha-2-HS-glycoprotein, Alpha-fetoprotein, Angiopoietin-1, Antileukoproteinase, Apolipoprotein(a), Cancer Antigen 15-3, Cancer Antigen 19-9, Carbonic anhydrase 9, Carcinoembryonic antigen-related cell adhesion molecule 5, C—C motif chemokine 1, C—C motif chemokine 13, C—C motif chemokine 15, C—C motif chemokine 17, C—C motif chemokine 19, C—C motif chemokine 20, C—C motif chemokine 21, C—C motif chemokine 22, C—C motif chemokine 23, C—C motif chemokine 24, C—C motif chemokine 26, C—C motif chemokine 27, C—C motif chemokine 3, C—C motif chemokine 4, C—C motif chemokine 7, C—C motif chemokine 8, Ceruloplasmin, Choriogonadotropin subunit beta, Collagenase 3, C-Peptide, Creatine Kinase-MB, C—X—C motif chemokine 10, C—X—C motif chemokine 11, C—X—C motif chemokine 13, C—X—C motif chemokine 16, C—X—C motif chemokine 5, C—X—C motif chemokine 6, C—X—C motif chemokine 9, Cystatin-C, Endothelial protein C receptor, Eotaxin, Epidermal growth factor receptor, Ferritin, Fibrinogen, Gastric inhibitory polypeptide, Glucagon, Glucagon-like peptide 1, Granulocyte-macrophage colony-stimulating factor, Growth-regulated alpha, beta, and gamma proteins, Heparin-binding growth factor 2, Hepatocyte growth factor, Immuno globulin A, Immunoglobulin M, Immunoglogulin G1, Immunoglogulin G2, Immunoglogulin G3, Immunoglogulin G4, Insulin, Insulin-like growth factor-binding protein 1, Insulin-like growth factor-binding protein 2, Insulin-like growth factor-binding protein 3, Insulin-like growth factor-binding protein 4, Insulin-like growth factor-binding protein 5, Insulin-like growth factor-binding protein 6, Insulin-like growth factor-binding protein 7, Interferon alpha-2, Interferon gamma, Interleukin-1 alpha, Interleukin-1 beta, Interleukin-1 receptor antagonist protein, Interleukin-1 receptor type I, Interleukin-1 receptor type II, Interleukin-11, Interleukin-12, Interleukin-12 subunit beta, Interleukin-13, Interleukin-15, Interleukin-2, Interleukin-20, Interleukin-21, Interleukin-23, Interleukin-28A, Interleukin-29, Interleukin-3, Interleukin-33, Interleukin-4, Interleukin-5, Interleukin-6 receptor subunit alpha, Interleukin-6 receptor subunit beta, Interleukin-7, Interleukin-9, Interstitial collagenase, Islet amyloid polypeptide, Keratin, type I cytoskeletal 19 (aa311-367), Kit ligand, Leptin, Leukemia inhibitory factor, Lymphotactin, Lymphotoxin-alpha, Macrophage colony-stimulating factor 1, Macrophage metalloelastase, Macrophage migration inhibitory factor, Matrilysin, Metalloproteinase inhibitor 1, Metalloproteinase inhibitor 2, Metalloproteinase inhibitor 3, Metalloproteinase inhibitor 4, Myoglobin, Pancreatic prohormone, Peptide YY, Pro-epidermal growth factor, Pro-interleukin-16, Prolactin, Prostate-specific antigen, Protein S100-A12, Protransforming growth factor alpha, Secretory immunoglobulin A, Serum amyloid P-component, SL cytokine, Stromal cell-derived factor 1, Stromelysin-1, Thrombopoietin, Thymic stromal lymphopoietin, Tumor necrosis factor, Tumor necrosis factor ligand superfamily member 10, Tumor necrosis factor ligand superfamily member 6, Tumor necrosis factor receptor superfamily member 1A, Tumor necrosis factor receptor superfamily member 1B, Vascular endothelial growth factor receptor 1, Vascular endothelial growth factor receptor 2, Vascular endothelial growth factor receptor 3, von Willebrand Factor, and WAP four-disulfide core domain protein 2 on a body fluid sample obtained from the subject to provide one or more assay result(s);
- and
- correlating the assay result(s) to the occurrence or nonoccurrence of appendicitis in the subject or likelihood of the future outcome to the subject.
A method for evaluating biomarker levels in a body fluid sample, comprising:
- obtaining a body fluid sample from a subject selected for evaluation based on a determination that the subject is experiencing symptoms indicative of possible acute appendicitis;
- and
- performing one or more analyte binding assays configured to detect one or more biomarkers selected from the group consisting of 72 kDa type IV collagenase, Adiponectin, Advanced glycosylation end product-specific receptor, Alpha-2 macroglobulin, Alpha-2-HS-glycoprotein, Alpha-fetoprotein, Angiopoietin-1, Antileukoproteinase, Apolipoprotein(a), Cancer Antigen 15-3, Cancer Antigen 19-9, Carbonic anhydrase 9, Carcinoembryonic antigen-related cell adhesion molecule 5, C—C motif chemokine 1, C—C motif chemokine 13, C—C motif chemokine 15, C—C motif chemokine 17, C—C motif chemokine 19, C—C motif chemokine 20, C—C motif chemokine 21, C—C motif chemokine 22, C—C motif chemokine 23, C—C motif chemokine 24, C—C motif chemokine 26, C—C motif chemokine 27, C—C motif chemokine 3, C—C motif chemokine 4, C—C motif chemokine 7, C—C motif chemokine 8, Ceruloplasmin, Choriogonadotropin subunit beta, Collagenase 3, C-Peptide, Creatine Kinase-MB, C—X—C motif chemokine 10, C—X—C motif chemokine 11, C—X—C motif chemokine 13, C—X—C motif chemokine 16, C—X—C motif chemokine 5, C—X—C motif chemokine 6, C—X—C motif chemokine 9, Cystatin-C, Endothelial protein C receptor, Eotaxin, Epidermal growth factor receptor, Ferritin, Fibrinogen, Gastric inhibitory polypeptide, Glucagon, Glucagon-like peptide 1, Granulocyte-macrophage colony-stimulating factor, Growth-regulated alpha, beta, and gamma proteins, Heparin-binding growth factor 2, Hepatocyte growth factor, Immunoglobulin A, Immunoglobulin M, Immunoglogulin G1, Immunoglogulin G2, Immunoglogulin G3, Immunoglogulin G4, Insulin, Insulin-like growth factor-binding protein 1, Insulin-like growth factor-binding protein 2, Insulin-like growth factor-binding protein 3, Insulin-like growth factor-binding protein 4, Insulin-like growth factor-binding protein 5, Insulin-like growth factor-binding protein 6, Insulin-like growth factor-binding protein 7, Interferon alpha-2, Interferon gamma, Interleukin-1 alpha, Interleukin-1 beta, Interleukin-1 receptor antagonist protein, Interleukin-1 receptor type I, Interleukin-1 receptor type II, Interleukin-11, Interleukin-12, Interleukin-12 subunit beta, Interleukin-13, Interleukin-15, Interleukin-2, Interleukin-20, Interleukin-21, Interleukin-23, Interleukin-28A, Interleukin-29, Interleukin-3, Interleukin-33, Interleukin-4, Interleukin-5, Interleukin-6 receptor subunit alpha, Interleukin-6 receptor subunit beta, Interleukin-7, Interleukin-9, Interstitial collagenase, Islet amyloid polypeptide, Keratin, type I cytoskeletal 19 (aa311-367), Kit ligand, Leptin, Leukemia inhibitory factor, Lymphotactin, Lymphotoxin-alpha, Macrophage colony-stimulating factor 1, Macrophage metalloelastase, Macrophage migration inhibitory factor, Matrilysin, Metalloproteinase inhibitor 1, Metalloproteinase inhibitor 2, Metalloproteinase inhibitor 3, Metalloproteinase inhibitor 4, Myoglobin, Pancreatic prohormone, Peptide YY, Pro-epidermal growth factor, Pro-interleukin-16, Prolactin, Prostate-specific antigen, Protein S100-A12, Protransforming growth factor alpha, Secretory immunoglobulin A, Serum amyloid P-component, SL cytokine, Stromal cell-derived factor 1, Stromelysin-1, Thrombopoietin, Thymic stromal lymphopoietin, Tumor necrosis factor, Tumor necrosis factor ligand superfamily member 10, Tumor necrosis factor ligand superfamily member 6, Tumor necrosis factor receptor superfamily member 1A, Tumor necrosis factor receptor superfamily member 1B, Vascular endothelial growth factor receptor 1, Vascular endothelial growth factor receptor 2, Vascular endothelial growth factor receptor 3, von Willebrand Factor, and WAP four-disulfide core domain protein 2 by introducing the body fluid sample obtained from the subject into an assay instrument which (i) contacts the body fluid sample with one or more binding reagents corresponding to the biomarker(s) being assayed, wherein each biomarker which is assayed binds to its respective specific binding reagent in an amount related to its concentration in the body fluid sample, (ii) generates one or more assay results indicative of binding of each biomarker which is assayed to its respective specific binding reagent;
- and (iii) displays the one or more assay results as a quantitative result in a human-readable form.
A method for evaluating biomarker levels in a body fluid sample, comprising:
- obtaining a body fluid sample from a subject selected for evaluation based on a determination that the subject has been diagnosed with acute appendicitis;
- and
- performing one or more analyte binding assays configured to detect one or more biomarkers selected from the group consisting of 72 kDa type IV collagenase, Adiponectin, Advanced glycosylation end product-specific receptor, Alpha-2 macroglobulin, Alpha-2-HS-glycoprotein, Alpha-fetoprotein, Angiopoietin-1, Antileukoproteinase, Apolipoprotein(a), Cancer Antigen 15-3, Cancer Antigen 19-9, Carbonic anhydrase 9, Carcinoembryonic antigen-related cell adhesion molecule 5, C—C motif chemokine 1, C—C motif chemokine 13, C—C motif chemokine 15, C—C motif chemokine 17, C—C motif chemokine 19, C—C motif chemokine 20, C—C motif chemokine 21, C—C motif chemokine 22, C—C motif chemokine 23, C—C motif chemokine 24, C—C motif chemokine 26, C—C motif chemokine 27, C—C motif chemokine 3, C—C motif chemokine 4, C—C motif chemokine 7, C—C motif chemokine 8, Ceruloplasmin, Choriogonadotropin subunit beta, Collagenase 3, C-Peptide, Creatine Kinase-MB, C—X—C motif chemokine 10, C—X—C motif chemokine 11, C—X—C motif chemokine 13, C—X—C motif chemokine 16, C—X—C motif chemokine 5, C—X—C motif chemokine 6, C—X—C motif chemokine 9, Cystatin-C, Endothelial protein C receptor, Eotaxin, Epidermal growth factor receptor, Ferritin, Fibrinogen, Gastric inhibitory polypeptide, Glucagon, Glucagon-like peptide 1, Granulocyte-macrophage colony-stimulating factor, Growth-regulated alpha, beta, and gamma proteins, Heparin-binding growth factor 2, Hepatocyte growth factor, Immunoglobulin A, Immunoglobulin M, Immunoglogulin G1, Immunoglogulin G2, Immunoglogulin G3, Immunoglogulin G4, Insulin, Insulin-like growth factor-binding protein 1, Insulin-like growth factor-binding protein 2, Insulin-like growth factor-binding protein 3, Insulin-like growth factor-binding protein 4, Insulin-like growth factor-binding protein 5, Insulin-like growth factor-binding protein 6, Insulin-like growth factor-binding protein 7, Interferon alpha-2, Interferon gamma, Interleukin-1 alpha, Interleukin-1 beta, Interleukin-1 receptor antagonist protein, Interleukin-1 receptor type I, Interleukin-1 receptor type II, Interleukin-11, Interleukin-12, Interleukin-12 subunit beta, Interleukin-13, Interleukin-15, Interleukin-2, Interleukin-20, Interleukin-21, Interleukin-23, Interleukin-28A, Interleukin-29, Interleukin-3, Interleukin-33, Interleukin-4, Interleukin-5, Interleukin-6 receptor subunit alpha, Interleukin-6 receptor subunit beta, Interleukin-7, Interleukin-9, Interstitial collagenase, Islet amyloid polypeptide, Keratin, type I cytoskeletal 19 (aa311-367), Kit ligand, Leptin, Leukemia inhibitory factor, Lymphotactin, Lymphotoxin-alpha, Macrophage colony-stimulating factor 1, Macrophage metalloelastase, Macrophage migration inhibitory factor, Matrilysin, Metalloproteinase inhibitor 1, Metalloproteinase inhibitor 2, Metalloproteinase inhibitor 3, Metalloproteinase inhibitor 4, Myoglobin, Pancreatic prohormone, Peptide YY, Pro-epidermal growth factor, Pro-interleukin-16, Prolactin, Prostate-specific antigen, Protein S100-A12, Protransforming growth factor alpha, Secretory immunoglobulin A, Serum amyloid P-component, SL cytokine, Stromal cell-derived factor 1, Stromelysin-1, Thrombopoietin, Thymic stromal lymphopoietin, Tumor necrosis factor, Tumor necrosis factor ligand superfamily member 10, Tumor necrosis factor ligand superfamily member 6, Tumor necrosis factor receptor superfamily member 1A, Tumor necrosis factor receptor superfamily member 1B, Vascular endothelial growth factor receptor 1, Vascular endothelial growth factor receptor 2, Vascular endothelial growth factor receptor 3, von Willebrand Factor, and WAP four-disulfide core domain protein 2 by introducing the body fluid sample obtained from the subject into an assay instrument which (i) contacts the body fluid sample with one or more binding reagents corresponding to the biomarker(s) being assayed, wherein each biomarker which is assayed binds to its respective specific binding reagent in an amount related to its concentration in the body fluid sample, (ii) generates one or more assay results indicative of binding of each biomarker which is assayed to its respective specific binding reagent;
- and (iii) displays the one or more assay results as a quantitative result in a human-readable form.
A system for evaluating biomarker levels, comprising:
- a plurality of reagents which specifically bind for detection a plurality of biomarkers selected from the group consisting of 72 kDa type IV collagenase, Adiponectin, Advanced glycosylation end product-specific receptor, Alpha-2 macroglobulin, Alpha-2-HS-glycoprotein, Alpha-fetoprotein, Angiopoietin-1, Antileukoproteinase, Apolipoprotein(a), Cancer Antigen 15-3, Cancer Antigen 19-9, Carbonic anhydrase 9, Carcinoembryonic antigen-related cell adhesion molecule 5, C—C motif chemokine 1, C—C motif chemokine 13, C—C motif chemokine 15, C—C motif chemokine 17, C—C motif chemokine 19, C—C motif chemokine 20, C—C motif chemokine 21, C—C motif chemokine 22, C—C motif chemokine 23, C—C motif chemokine 24, C—C motif chemokine 26, C—C motif chemokine 27, C—C motif chemokine 3, C—C motif chemokine 4, C—C motif chemokine 7, C—C motif chemokine 8, Ceruloplasmin, Choriogonadotropin subunit beta, Collagenase 3, C-Peptide, Creatine Kinase-MB, C—X—C motif chemokine 10, C—X—C motif chemokine 11, C—X—C motif chemokine 13, C—X—C motif chemokine 16, C—X—C motif chemokine 5, C—X—C motif chemokine 6, C—X—C motif chemokine 9, Cystatin-C, Endothelial protein C receptor, Eotaxin, Epidermal growth factor receptor, Ferritin, Fibrinogen, Gastric inhibitory polypeptide, Glucagon, Glucagon-like peptide 1, Granulocyte-macrophage colony-stimulating factor, Growth-regulated alpha, beta, and gamma proteins, Heparin-binding growth factor 2, Hepatocyte growth factor, Immunoglobulin A, Immunoglobulin M, Immunoglogulin G1, Immunoglogulin G2, Immunoglogulin G3, Immunoglogulin G4, Insulin, Insulin-like growth factor-binding protein 1, Insulin-like growth factor-binding protein 2, Insulin-like growth factor-binding protein 3, Insulin-like growth factor-binding protein 4, Insulin-like growth factor-binding protein 5, Insulin-like growth factor-binding protein 6, Insulin-like growth factor-binding protein 7, Interferon alpha-2, Interferon gamma, Interleukin-1 alpha, Interleukin-1 beta, Interleukin-1 receptor antagonist protein, Interleukin-1 receptor type I, Interleukin-1 receptor type II, Interleukin-11, Interleukin-12, Interleukin-12 subunit beta, Interleukin-13, Interleukin-15, Interleukin-2, Interleukin-20, Interleukin-21, Interleukin-23, Interleukin-28A, Interleukin-29, Interleukin-3, Interleukin-33, Interleukin-4, Interleukin-5, Interleukin-6 receptor subunit alpha, Interleukin-6 receptor subunit beta, Interleukin-7, Interleukin-9, Interstitial collagenase, Islet amyloid polypeptide, Keratin, type I cytoskeletal 19 (aa311-367), Kit ligand, Leptin, Leukemia inhibitory factor, Lymphotactin, Lymphotoxin-alpha, Macrophage colony-stimulating factor 1, Macrophage metalloelastase, Macrophage migration inhibitory factor, Matrilysin, Metalloproteinase inhibitor 1, Metalloproteinase inhibitor 2, Metalloproteinase inhibitor 3, Metalloproteinase inhibitor 4, Myoglobin, Pancreatic prohormone, Peptide YY, Pro-epidermal growth factor, Pro-interleukin-16, Prolactin, Prostate-specific antigen, Protein S100-A12, Protransforming growth factor alpha, Secretory immunoglobulin A, Serum amyloid P-component, SL cytokine, Stromal cell-derived factor 1, Stromelysin-1, Thrombopoietin, Thymic stromal lymphopoietin, Tumor necrosis factor, Tumor necrosis factor ligand superfamily member 10, Tumor necrosis factor ligand superfamily member 6, Tumor necrosis factor receptor superfamily member 1A, Tumor necrosis factor receptor superfamily member 1B, Vascular endothelial growth factor receptor 1, Vascular endothelial growth factor receptor 2, Vascular endothelial growth factor receptor 3, von Willebrand Factor, and WAP four-disulfide core domain protein 2;
- an assay instrument configured to (i) receive a body fluid sample, (ii) contact the plurality of reagents with the body fluid sample and (iii) generate and quantitatively display in human readable form one or more assay results indicative of binding of each biomarker which is assayed to a respective specific binding reagent in the plurality of reagents.
Dependencies are inferred from the claim text.