Use of soluble trem-1 levels for identifying subjects susceptible to respond to an anti-inflammatory therapy

Abstract

A method for identifying human subjects suffering from an inflammatory disorder susceptible to respond to a therapy, in particular to a TREM-1 inhibitor. In particular, an in vitro method for identifying a human subject suffering from an inflammatory disorder, preferably an acute inflammatory disorder such as SIRS, sepsis or septic shock, susceptible to respond to a therapy, in particular to a TREM-1 inhibitor. The method includes the steps of a) measuring the level of soluble triggering receptors expressed on myeloid cells-1 (sTREM-1) in a biological sample from the human subject, comparing the level of sTREM-1 measured at step a) to a predetermined sTREM-1 value, and c) identifying a human subject suffering from an inflammatory disorder with a level of sTREM-1 measured at step a) higher than the predetermined sTREM-1 value of step b) as susceptible to respond to a therapy, in particular to a TREM-1 inhibitor.

1 - 15 . (canceled) 
     
     
         16 . A method for treating an inflammatory disorder in a human subject identified as susceptible to respond to a therapy, said method comprising:
 identifying a human subject suffering from an inflammatory disorder susceptible to respond to a therapy by:
 a) measuring the level of soluble Triggering Receptors Expressed on Myeloid cells-1 (sTREM-1) in a biological sample from the human subject; 
 b) comparing the level of sTREM-1 measured at step a) to a predetermined sTREM-1 value; 
 c) identifying a human subject suffering from an inflammatory disorder with a level of sTREM-1 measured at step a) higher than the predetermined sTREM-1 value of step b) as susceptible to respond to a therapy; 
   administering a therapy to the subject suffering from an inflammatory disorder identified as being susceptible to respond to a therapy.   
     
     
         17 . The method according to  claim 16 , wherein the predetermined sTREM-1 value of step b) is obtained from a reference population. 
     
     
         18 . The method according to  claim 17 , wherein the reference population is a population of human patients suffering from an inflammatory disorder. 
     
     
         19 . The method according to  claim 17 , wherein the reference population is a population of human patients suffering from systemic inflammatory response syndrome (SIRS), sepsis or septic shock. 
     
     
         20 . The method according to  claim 17 , wherein the predetermined sTREM-1 value of step b) is the sTREM-1 median in the reference population or the sTREM-1 third quartile in the reference population. 
     
     
         21 . The method according to  claim 16 , wherein the level of sTREM-1 measured at step a) is a level measured before the beginning of the therapy. 
     
     
         22 . The method according to  claim 16 , wherein the level of sTREM-1 measured at step a) is measured within the first 24 hours following the diagnosis or the hospitalization of the human subject for an inflammatory disorder. 
     
     
         23 . The method according to  claim 16 , wherein the biological sample is a blood sample, a serum sample or a plasma sample. 
     
     
         24 . The method according to  claim 16 , wherein the level of sTREM-1 measured at step a) is a protein level. 
     
     
         25 . The method according to  claim 16 , wherein the level of sTREM-1 measured at step a) is a protein level measured by enzyme-linked immunosorbent assay (ELISA), electrochemiluminescence immunoassay (ECLIA) or enzyme-linked fluorescent assay (ELFA). 
     
     
         26 . The method according to  claim 16 , wherein the therapy is a Triggering Receptors Expressed on Myeloid cells-1 (TREM-1) inhibitor. 
     
     
         27 . The method according to  claim 26 , wherein the TREM-1 inhibitor is selected from the group consisting of peptides inhibiting the function, activity or expression of TREM-1; antibodies directed to TREM-1 and/or sTREM-1, or TREM-1 and/or sTREM-1 ligand; small molecules inhibiting the function, activity or expression of TREM-1; siRNAs directed to TREM-1; shRNAs directed to TREM-1; antisense oligonucleotide directed to TREM-1; ribozymes directed to TREM-1; and aptamers directed to TREM-1. 
     
     
         28 . The method according to  claim 27 , wherein the TREM-1 inhibitor is a peptide inhibiting the function, activity or expression of TREM-1 by targeting TREM-1 ligand. 
     
     
         29 . The method according to  claim 27 , wherein the TREM-1 inhibitor is a peptide of 6 to 20 amino acids comprising an amino acid sequence as set forth in SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, or SEQ ID NO: 12, or an amino acid sequence having at least 90% identity with the amino acid sequence as set forth in SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, or SEQ ID NO: 12. 
     
     
         30 . The method according to  claim 27 , wherein the TREM-1 inhibitor is a peptide having an amino acid sequence as set forth in SEQ ID NO: 9 or an amino acid sequence having at least 90% identity with the amino acid sequence as set forth in SEQ ID NO: 9. 
     
     
         31 . The method according to  claim 16 , wherein the inflammatory disorder is selected from the group consisting of systemic inflammatory response syndrome (SIRS), sepsis, and septic shock. 
     
     
         32 . The method according to  claim 16 , wherein the human subject is suffering from an organ dysfunction defined as an acute change in his/her sequential organ failure assessment (SOFA) score of at least 2 points. 
     
     
         33 . The method according to  claim 31 , wherein a human subject suffering from SIRS, sepsis or septic shock susceptible to respond to a therapy is a human subject susceptible to have his/her sequential organ failure assessment (SOFA) score decrease following the administration of the therapy. 
     
     
         34 . The method according to  claim 31 , wherein a human subject suffering from septic shock susceptible to respond to a therapy is a human subject suffering from septic shock susceptible to reverse a hypotensive shock within or after the administration period of the therapy, wherein a hypotensive shock reversal is defined as the absence of any vasopressor therapy during 24 hours. 
     
     
         35 . An in vitro method for identifying a human subject suffering from an inflammatory disorder susceptible to respond to a therapy, said method comprising:
 a) measuring the level of soluble Triggering Receptors Expressed on Myeloid cells-1 (sTREM-1) in a biological sample from the human subject;   b) comparing the level of sTREM-1 measured at step a) to a predetermined sTREM-1 value;   c) identifying a human subject suffering from an inflammatory disorder with a level of sTREM-1 measured at step a) higher than the predetermined sTREM-1 value of step b) as susceptible to respond to a therapy.