COPD Biomarker Signatures
The present invention relates to methods of detecting differentially expressed protein expression indicative of COPD in a test sample. The detection of circulating levels of proteins within an identified COPD biomarker signature can aid in COPD diagnosis and disease monitoring, as well as in the prediction of responses to therapeutics. Evaluation of the biomarker signatures disclosed, or a subset of biomarkers thereof, provides a level of discrimination not found with individual markers.
1 - 20 . (canceled)
21 . A kit, comprising first antibodies or first antibody fragments for detecting at least three protein markers, or corresponding peptides thereof, selected from each of two or more multi-analyte panels selected from the group consisting of:
multi-analyte panel (a) apolipoprotein H, CD40, haptoglobin, interleukin-8 (IL-8), monocyte chemoattractant protein-1 (MCP-1) and tumor necrosis factor receptor II (TNF-RII);
multi-analyte panel (b) apolipoprotein CIII, CD40, granulocyte-macrophage colony stimulating factor (GM-CSF), haptoglobin, immunoglobulin A (IgA), macrophage inflammatory protein 1alpha (MIP-1α), tissue factor and tumor necrosis factor-alpha (TNF-α); and
multi-analyte panel (c) alpha-1 antitrypsin, C-reactive protein (CRP), fibrinogen, granulocyte-macrophage colony stimulating factor (GM-CSF), interleukin-4 (IL-4), macrophage-derived chemokine (MDC), tissue factor, tumor necrosis factor receptor II (TNFRII) and soluble vascular cell adhesion molecule 1 (sVCAM-1);
wherein said first antibodies or first antibody fragments are bound to a solid phase or labeled with a detectable label.
22 . The kit of claim 21 , wherein said first antibodies or first antibody fragments are bound to a solid phase selected from the group consisting of a bead, plate, membrane, or array.
23 . The kit of claim 22 , wherein, for each first antibody or first antibody fragment provided in the kit that binds to a subject protein marker, the kit further comprises a second antibody or second antibody fragment that binds to the same subject protein marker.
24 . The kit of claim 23 , wherein said second antibodies or second antibody fragments are detectably labeled.
25 . The kit of claim 24 , wherein said second antibodies or second antibody fragments are detectably labeled for detection by microscopy, fluorescence, luminescence, chemiluminescence, absorbance, reflectance, transmittance, or birefringence.
26 . The kit of claim 24 , wherein said second antibodies or second antibody fragments are detectably labeled for detection by enzyme-linked immunosorbent assays (ELISA) or radioimmunoassay (RIA).
27 . The kit of claim 21 , wherein the kit comprises first antibodies or first antibody fragments for each protein marker of two or more of the multi-analyte panels.
28 . A composition comprising first antibodies or first antibody fragments for detecting at least three protein markers, or peptides thereof, selected from each of two or more multi-analyte panels selected from the group consisting of:
multi-analyte panel (a) apolipoprotein H, CD40, haptoglobin, interleukin-8 (IL-8), monocyte chemoattractant protein-1 (MCP-1) and tumor necrosis factor receptor II (TNF-RII);
multi-analyte panel (b) apolipoprotein CIII, CD40, granulocyte-macrophage colony stimulating factor (GM-CSF), haptoglobin, immunoglobulin A (IgA), macrophage inflammatory protein 1alpha (MIP-1α), tissue factor and tumor necrosis factor-alpha (TNF-α); and
multi-analyte panel (c) alpha-1 antitrypsin, C-reactive protein (CRP), fibrinogen, granulocyte-macrophage colony stimulating factor (GM-CSF), interleukin-4 (IL-4), macrophage-derived chemokine (MDC), tissue factor, tumor necrosis factor receptor II (TNFRII) and soluble vascular cell adhesion molecule 1 (sVCAM-1);
wherein said first antibodies or first antibody fragments are bound to a solid phase, and wherein the composition does not comprise antibodies against at least one of the proteins in the multi-analyte panels.
29 . The composition of claim 28 , wherein said first antibodies or first antibody fragments are bound to a solid phase or detectably labeled.
30 . The composition of claim 28 , wherein, for each first antibody or first antibody fragment provided in the composition that binds to a subject protein marker, the composition further comprises a second antibody or second antibody fragment that binds to the same subject protein marker.
31 . The composition of claim 30 , wherein the second antibodies or second antibody fragments to each of the three or more protein markers or corresponding peptides thereof are detectably labeled.