Diagnosis of sepsis or SIRS using biomarker profiles
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Abstract
The early prediction or diagnosis of sepsis advantageously allows for clinical intervention before the disease rapidly progresses beyond initial stages to the more severe stages, such as severe sepsis or septic shock, which are associated with high mortality. Early prediction or diagnosis is accomplished by comparing an individual'"'"'s profile of biomarker expression to profiles obtained from one or more control, or reference, populations, which may include a population that develops sepsis. Recognition of features in the individual'"'"'s biomarker profile that are characteristic of the onset of sepsis allows a clinician to diagnose the onset of sepsis from a bodily fluid isolated from the individual at a single point in time. The necessity of monitoring the patient over a period of time is, therefore, avoided, advantageously allowing clinical intervention before the onset of serious symptoms of sepsis. Further, because the biomarker expression is assayed for its profile, identification of the particular biomarkers is unnecessary. The comparison of an individual'"'"'s biomarker profile to biomarker profiles of appropriate reference populations likewise can be used to diagnose SIRS in the individual.
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Citations
128 Claims
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1-91. -91. (canceled)
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92. A method of predicting sepsis in a human SIRS patient comprising
a) determining the abundances of at least three biomarker proteins in a blood or plasma sample from a human SIRS patient, wherein the three biomarker proteins are selected from apolipoprotein A1 (apoA1), apolipoprotein CIII (apoCIII), β - -2 microglobulin (β
2M), C reactive protein (CRP), macrophage chemoattractant protein-1 (MCP-1), matrix metalloproteinase-9 (MMP-9), macrophage inflammatory protein-1β
(MIP-1β
), serum amyloid P (SAP) and tissue inhibitor of metalloproteinase-1 (TIMP-1); andb) comparing the abundances of the biomarker proteins in the sample to features corresponding to abundances of the at least three biomarker proteins present in a first reference profile taken from a SIRS-positive human reference population that did not progress to sepsis, wherein sepsis is predicted in the SIRS patient when it is determined that the abundances of the at least three biomarker proteins are (i) greater than the abundances in the first reference profile where the biomarker proteins are β
2M, CRP, MCP-1, MMP-9, MIP-1β
, SAP or TIMP-1, or (ii) less than the abundances in the first reference profile where the biomarker proteins are apoA1 or apoCIII. - View Dependent Claims (93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124)
- -2 microglobulin (β
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125. A method of predicting sepsis in a human SIRS patient comprising
a) determining the abundances of at least three proteins in a first blood or plasma sample from a human SIRS patient, wherein the three proteins are selected from apoA1, apoCIII, β - 2M, CRP, MCP-1, MMP-9, MIP-1β
, SAP and TIMP-1;b) determining the abundances of the at least three proteins in a second blood or plasma sample from a human SIRS patient; and c) comparing the abundances of the proteins in the second blood or plasma sample to features corresponding to abundances of the at least three proteins present in the first blood or plasma sample, wherein sepsis is predicted in the SIRS patient when it is determined that the abundances of the at least three protein in the second blood or plasma sample are (i) greater than the abundances in the first blood or plasma sample where the proteins are β
2M, CRP, MCP-1, MMP-9, MIP-1β
, SAP or TIMP-1, or (ii) less than the abundances in the first blood or plasma sample where the proteins are apoA1 or apoCIII. - View Dependent Claims (126)
- 2M, CRP, MCP-1, MMP-9, MIP-1β
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127. A method of determining that a SIRS patient is not likely to develop sepsis comprising
a) detecting abundances of at least three biomarker proteins in a blood or plasma sample from a human SIRS patient, wherein the three biomarker proteins are selected from apolipoprotein A1 (apoA1), apolipoprotein CIII (apoCIII), β - -2 microglobulin (β
2M), C reactive protein (CRP), macrophage chemoattractant protein-1 (MCP-1), matrix metalloproteinase-9 (MMP-9), macrophage inflammatory protein-1β
(MIP-1β
), serum amyloid P (SAP) and tissue inhibitor of metalloproteinase-1 (TIMP-1); andb) comparing the abundances of the biomarker proteins in the sample to features corresponding to abundances of the at least three biomarker proteins present in a first reference profile taken from a SIRS-positive human reference population that progressed to sepsis, wherein it is determined that the SIRS patient is not likely to develop sepsis within 48 hours from when the blood or plasma sample was taken from the SIRS patient when the abundances of the at least three biomarker proteins in the sample differ from those in the first reference profile. - View Dependent Claims (128)
- -2 microglobulin (β
Specification