Proadm and/or histones as markers indicating an adverse event

Abstract

The present invention relates to diagnosis, prognosis, risk assessment, and/or risk stratification of an adverse event, particularly mortality, of a subject. The invention relates to a method that comprises determining a level of proadrenomedullin (proADM) in a sample of said subject, and wherein said level of proADM is indicative of said adverse event of said subject, wherein said level of proADM is compared to a reference level of proADM; and wherein said adverse event of said subject is identified based on the comparison. The invention further relates to kits for carrying out the methods of the invention.

1 . A method for detecting proadrenomedullin (proADM) in a subject in need thereof, the method comprising:
 determining in a sample obtained from the subject whether the level of proADM is < about 0.88 nmol/L or is ≥ about 0.88 nmol/L using an immunoassay.   
     
     
         2 . The method of  claim 1 , wherein said subject suffers from a disease or medical condition. 
     
     
         3 . The method of  claim 2 , wherein said subject is a critically ill patient. 
     
     
         4 . The method of  claim 3 , wherein said subject is admitted to an intensive care unit or an emergency department. 
     
     
         5 . The method of  claim 1 , wherein the determined level of proADM is used in the calculation of a diagnostic score. 
     
     
         6 . The method of  claim 5 , wherein additionally at least one further marker and or parameter of the subject is used for the calculation of said score. 
     
     
         7 . The method of  claim 6 , wherein the at least one further marker and/or parameter of said subject is selected from the group consisting of a level of at least one histone, a level of procalcitonin (PCT) in said sample, the simplified acute physiology score (SAPSII score), the quick SOFA (qSOFA) score, the Acute Physiology and Chronic Health Evaluation II (APACHE II) score of said subject, the Pneumonia Severity Index (PSI) score of said subject and the CURB-65 score of said subject. 
     
     
         8 . The method of  claim 1 , additionally comprising determining the sequential organ failure assessment (SOFA) score of the subject. 
     
     
         9 . The method of  claim 8 , wherein the SOFA score is increased when the determined level of proADM is ≥ about 0.88 nmol/L to result in a modified SOFA score. 
     
     
         10 . The method of  claim 1 , wherein said proADM is midregional proadrenomedullin (MR-proADM) or mature ADM. 
     
     
         11 . The method of  claim 1 , wherein said method further comprises determining at least one marker and/or parameter of said subject selected from the group consisting of a level of at least one histone, a level of procalcitonin (PCT) in said sample, the simplified acute physiology score (SAPSII score), the quick SOFA (qSOFA) score, the Acute Physiology and Chronic Health Evaluation II (APACHE II) score of said subject, the Pneumonia Severity Index (PSI) score of said subject and the CURB-65 score of said subject. 
     
     
         12 . The method of  claim 1 , wherein said subject suffers from a disease or medical condition and wherein said disease or medical condition is selected from the group consisting of respiratory disease, urinary tract infection, an inflammatory response related to infective and non-infective etiologies, systemic inflammatory response syndrome (SIRS), sepsis, severe sepsis, septic shock, organ failure(s), cardiovascular disease, diabetes mellitus, malignancy, liver disease, renal disease, immunodepression, viral infection, fungal infection, bacterial infection, gram-negative bacterial infection, gram-positive bacterial infection and immunosuppression. 
     
     
         13 . The method of  claim 1 , wherein said subject suffers from sepsis. 
     
     
         14 . The method of  claim 1 , wherein said subject is an immunosuppressed subject, optionally a subject suffering from human immunodeficiency virus (HIV), a subject undergoing radiotherapy, and/or a subject receiving immunosuppressive drugs. 
     
     
         15 . The method of  claim 1 , wherein said sample is a body fluid, blood, blood plasma, blood serum, or urine. 
     
     
         16 . The method of  claim 1 , wherein said level of proADM is determined using a method selected from the group consisting of, luminescence immunoassay (LIA), radioimmunoassay (RIA), chemiluminescence- and fluorescence-immunoassays, enzyme immunoassay (EIA), Enzyme-linked immunoassays (ELISA), luminescence-based bead arrays, magnetic beads based arrays, protein microarray assays, rapid test formats, and rare cryptate assay. 
     
     
         17 . The method of  claim 5 , wherein the assay is performed in homogeneous phase or in heterogeneous phase. 
     
     
         18 . The method of  claim 5 , wherein the calculation is computer-implemented. 
     
     
         19 . A computer-system for performing the method of  claim 5 , comprising
 (i) a sample analyzer for determining the level of proADM in the sample of a subject; and   (ii) a computer sub-system programmed to calculate the diagnostic score for said subject.