Biomarkers for early determination of a critical or life threatening response to illness and/or treatment response

Abstract

The invention relates to the use of novel biomarkers and biomarker combinations having utility in the early determination of an individual's critical and/or life threatening response to illness and/or in predicting outcome of said illness. The measurement of expression levels of the products of the biomarkers and combinations of biomarkers of the invention have utility in making the determination of an individual's critical and/or life threatening response to illness. In some embodiments, the biomarker and biomarker combinations are agnostic and are independent of the pre-identification and/or determination of the cause or nature of the illness. In some embodiments, the biomarkers and biomarker combinations can be utilized to select treatment and/or monitor the effectiveness of treatment interventions for an individual who has a critical illness.

What is claimed is: 
     
         1 . A method of determining a likelihood of a test individual having a critical and/or life threatening response to a suspected illness, said method comprising:
 (i) detecting and quantifying a level of each of two protein biomarkers in a sample from the test individual, wherein the test individual has not been diagnosed or differentially diagnosed as having the suspected illness, wherein said protein biomarkers are: angiopoietin-2 (Ang-2) and soluble triggering receptor expressed on myeloid cells-1 (sTREM-1));   (ii) comparing said quantified levels of said protein biomarkers to control levels of said protein biomarkers from a control population; and   (iii) determining the differential levels for each biomarker in the comparison of step (ii) so as to make a determination as to whether said test individual is at an increased risk of having the critical and/or life threatening response.   
     
     
         2 - 3 . (canceled) 
     
     
         4 . The method of  claim 1 , wherein the determination of step (iii) is indicative of said individual requiring the application of a treatment protocol as a result of the increased risk identified. 
     
     
         5 . The method of  claim 4 , wherein said individual is subjected to the treatment protocol. 
     
     
         6 . The method of  claim 1 , wherein said control population is a population of individuals having a critical and/or life threatening illness. 
     
     
         7 . The method of  claim 1 , wherein said control population is a population of individuals having a critical and/or life threatening illness, wherein the individuals have not developing a critical and/or life threatening response to the illness. 
     
     
         8 . The method of  claim 1 , wherein said control population is a population of individuals having a critical and/or life threatening illness, wherein the individuals have developing a critical and/or life threatening response to the illness. 
     
     
         9 . The method of  claim 1 , wherein said control population is a population of individuals who are normal. 
     
     
         10 . The method of  claim 1 , wherein said control population is a population of individuals that do not have an illness which is critical and/or life threatening. 
     
     
         11 . The method of  claim 1 , wherein said control population is a population of individuals wherein the members of the control population do not have an illness which is critical and/or life threatening. 
     
     
         12 . The method of  claim 1 , wherein the illness is a pneumonia, an upper respiratory tract infection, a lower respiratory tract infection, an influenza, an  E. coli  infection, a bacteremia, a rickettsial infection,  salmonellosis , a streptococcal infection, a  staphylococcus  infection, malaria, sepsis, Dengue fever, west nile virus, toxic shock syndrome, leptospirosis, or a viral hemorrhagic fever. 
     
     
         13 . A method of determining a likelihood of a test individual having a critical and/or life threatening response to a suspected illness, said method comprising:
 (i) detecting and quantifying a level of each of two protein biomarkers in a sample from the test individual, wherein the test individual has not been diagnosed or differentially diagnosed as having the suspected illness, wherein said protein biomarkers are: angiopoietin-2 (Ang-2 and soluble triggering receptor expressed on myeloid cells-1 (sTREM-1);   (ii) utilizing the quantified levels of each said protein biomarkers from said sample in a classifier derived from testing said protein biomarkers in one or more control populations; and   (iii) making a determination as to whether said individual is an increased risk of a life threatening response as a result of application of said classifier.   
     
     
         14 - 15 . (canceled) 
     
     
         16 . The method of  claim 13 , wherein the determination of step (iii) is indicative of said individual requiring the application of a treatment protocol as a result of the increased risk identified. 
     
     
         17 . The method of  claim 16 , wherein said individual is subjected to the treatment protocol. 
     
     
         18 . The method of  claim 13 , wherein said classifier is derived using at least two control populations, a population of individuals having the suspected illness, and not having a critical and/or life threatening response to said suspected illness and a population of individuals having the suspected illness and having a critical and/or life threatening response to said illness. 
     
     
         19 . The method of  claim 13 , wherein said classifier is derived using at least two control populations, a population of individuals having an illness which can be critical and/or life threatening, and not having a critical and/or life threatening response to said illness and a population of individuals having an illness which can be critical and/or life threatening, and having a critical and/or life threatening response to said illness. 
     
     
         20 . The method of  claim 13 , wherein said classifier is derived using at least two control populations, a population of individuals considered normal and a population of individuals having an illness which can be critical and/or life threatening, and having a critical and/or life threatening response to said illness. 
     
     
         21 . The method of  claim 13 , wherein the suspected illness is a pneumonia, an upper respiratory tract infection, a lower respiratory tract infection, an influenza, an  E. coli  infection, a bacteremia, a rickettsial infection,  salmonellosis , a streptococcal infection, a  staphylococcus  infection, malaria, sepsis, Dengue fever, west nile virus, toxic shock syndrome, leptospirosis, or a viral hemorrhagic fever. 
     
     
         22 - 42 . (canceled) 
     
     
         43 . A composition comprising a collection of two antibodies and a suitable buffer, said composition capable of selectively binding to two protein biomarkers from a sample isolated from a test individual suspected of having an illness, wherein the protein biomarkers are: angiopoietin-2 (Ang-2) and soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) and wherein the composition is used to quantify the level of said protein biomarkers in said sample and determine whether said test individual is at an increased risk of having a critical and/or life threatening response to the illness. 
     
     
         44 - 59 . (canceled) 
     
     
         60 . A method of determining whether the administration of a treatment protocol is likely to be useful in a test individual having presenting with one or more symptoms of an illness, said method comprising:
 (i) detecting and quantifying a level of each of two protein biomarkers in a sample from the test individual, wherein the illness of the test individual has not been diagnosed or differentially diagnosed, wherein said protein biomarkers are: angiopoietin-2 (Ang-2) and soluble triggering receptor expressed on myeloid cells-1 (sTREM-1)   (ii) utilizing the quantified levels of each said protein biomarkers from said sample in a classifier derived from testing said protein biomarkers in one or more control populations   (iii) making a determination as to whether said test individual is likely to benefit from the treatment protocol as a result of application of said classifier.   
     
     
         61 - 69 . (canceled) 
     
     
         70 . The method of  claim 21 , wherein the suspected illness is sepsis.