Diagnostic method employing hnl

Abstract

The present invention relates to the means and methods for the detection of bacterial infections, methods discriminating between viral and bacterial infections, methods of stratifying patients for subsequent treatment and further diagnostic purposes and methods to monitor antibiotherapy. The present invention is based on the detection of specific epitopes of human neutrophil lipocalin (HNL) using specific binding agents.

1 . A method of diagnosing a bacterial infection or differentiating a bacterial infection from a viral infection,
 wherein a blood, plasma, serum, urine, CSF, bone marrow, saliva, or sputum sample obtained from a subject suspected to have an infection is analyzed for the HNL level using a binding agent,   wherein the binding agent is configured to specifically bind to a polypeptide epitope of human neutrophil lipocalin (HNL) with a binding affinity,   wherein the binding agent comprises six murine complementarity-determining regions (CDRs),   wherein each of the CDRs are configured to bind to amino acids 141 to 156 of the human polypeptide epitope of HNL as defined in SEQ ID NO: 1,   wherein the HNL epitope is specifically bound,   wherein the binding affinity is at least 75% or higher compared with a binding specificity achieved with the CDRs, wherein the CDRs are depicted in SEQ ID Nos: 8 to 13, 14 to 19, or 20 to 25,   wherein the binding agent comprises a heavy chain variable region and a light chain variable region,   wherein the heavy chain variable region comprises a first set of the murine CDRs, the first set comprising:
 a first heavy chain CDR (CDRH1), wherein CDRH1 is SEQ ID NO: 11; 
 a second heavy chain CDR (CDRH2), wherein CDRH2 is SEQ ID NO: 12; and 
 a third heavy chain CDR (CDRH3), wherein CDRH3 is SEQ ID NO: 13, 
   wherein the light chain variable region comprises a second set of the murine CDRs, the second set comprising:
 a first light chain CDR (CDRL1), wherein CDRL1 SEQ ID NO: 8; 
 a second light chain CDR (CDRL2), wherein CDRL2 SEQ ID NO: 9; and 
 a third light chain CDR (CDRL3), wherein CDRL3 SEQ ID NO: 10, the method comprising: 
   incubating a sample in the presence of the binding agent;   measuring a level of HNL in a sample from a subject suspected to have an infection;   comparing the level of HNL measured with a control level;   diagnosing a bacterial infection when the level of HNL is significantly higher than the level detected in control samples of healthy subjects and of patients known to have a viral infection.   
     
     
         2 . The method of  claim 1 , further comprising at least one of:
 washing off unbound sample material after the incubating step; and   comparing the level of HNL measured with one or more control samples obtained from:
 healthy subjects; 
 subjects known to have a bacterial infection; and 
 subjects known to have a virus infection. 
   
     
     
         3 . The method of  claim 1 , further comprising:
 measuring a polypeptide concentration of TRAIL in a blood, plasma, serum, urine, CSF, bone marrow, saliva, or sputum sample obtained from a subject;
 recommending that the subject receives an antibiotic treatment if the polypeptide concentration of HNL measured is higher than a predetermined threshold value and if the concentration of TRAIL measured is lower than a predetermined threshold value; and 
 recommending that the patient does not receive an antibiotic treatment if the polypeptide concentration of HNL measured is lower than a predetermined threshold value and if the polypeptide concentration of TRAIL measured is higher than a predetermined threshold value or that the patient receives an anti-viral treatment if the polypeptide concentration of HNL measured is lower than a predetermined threshold value and if the polypeptide concentration of TRAIL measured is higher than a predetermined threshold value. 
   
     
     
         4 . The method according to  claim 1 ,
 wherein the binding agent has a heavy chain comprising the first set,   wherein the heavy chain comprises a heavy chain variable region sequence selected from the group consisting of sequences depicted in SEQ ID NO: 3,   wherein the binding agent has a light chain comprising the second set,   wherein the light chain comprises a light chain variable region sequence selected from the group consisting of sequences depicted in SEQ ID NO: 2.   
     
     
         5 . A method of ruling out an infection in a subject comprising:
 measuring a polypeptide concentration of HNL in a blood, plasma, serum, urine, CSF, bone marrow, saliva, or sputum sample obtained from a subject using a binding agent,   wherein the binding agent is configured to specifically bind to a polypeptide epitope of human neutrophil lipocalin (HNL) with a binding affinity,   wherein the binding agent comprises six murine complementarity-determining regions (CDRs),   wherein each of the CDRs are configured to bind to amino acids 141 to 156 of the human polypeptide epitope of HNL as defined in SEQ ID NO: 1,   wherein the HNL epitope is specifically bound,   wherein the binding affinity is at least 75% or higher compared with a binding specificity achieved with the CDRs, wherein the CDRs are depicted in SEQ ID Nos: 8 to 13, 14 to 19, or 20 to 25,   wherein the binding agent comprises a heavy chain variable region and a light chain variable region,   wherein the heavy chain variable region comprises a first set of the murine CDRs, the first set comprising:
 a first heavy chain CDR (CDRH1), wherein CDRH1 is SEQ ID NO: 11; 
 a second heavy chain CDR (CDRH2), wherein CDRH2 is SEQ ID NO: 12; and 
 a third heavy chain CDR (CDRH3), wherein CDRH3 is SEQ ID NO: 13, 
   wherein the light chain variable region comprises a second set of the murine CDRs, the second set comprising:
 a first light chain CDR (CDRL1), wherein CDRL1 SEQ ID NO: 8; 
 a second light chain CDR (CDRL2), wherein CDRL2 SEQ ID NO: 9; and 
   a third light chain CDR (CDRL3), wherein CDRL3 SEQ ID NO: 10; and   ruling out a bacterial infection for the subject if the polypeptide concentration of HNL determined is lower than a predetermined first threshold value or ruling out a viral infection for the subject if the polypeptide concentration of HNL determined is higher than a predetermined first threshold value.   
     
     
         6 . The method according to  claim 5 ,
 wherein the binding agent has a heavy chain comprising the first set,   wherein the heavy chain comprises a heavy chain variable region sequence selected from the group consisting of sequences depicted in SEQ ID NO: 3,   wherein the binding agent has a light chain comprising the second set,   wherein the light chain comprises a light chain variable region sequence selected from the group consisting of sequences depicted in SEQ ID NO: 2.   
     
     
         7 . A method of ruling in an infection in a subject comprising:
 measuring a polypeptide concentration of HNL in a blood, plasma, serum, urine, CSF, bone marrow, saliva, or sputum sample obtained from a subject using a binding agent,   wherein the binding agent is configured to specifically bind to a polypeptide epitope of human neutrophil lipocalin (HNL) with a binding affinity,   wherein the binding agent comprises six murine complementarity-determining regions (CDRs),   wherein each of the CDRs are configured to bind to amino acids 141 to 156 of the human polypeptide epitope of HNL as defined in SEQ ID NO: 1,   wherein the HNL epitope is specifically bound,   wherein the binding affinity is at least 75% or higher compared with a binding specificity achieved with the CDRs, wherein the CDRs are depicted in SEQ ID Nos: 8 to 13, 14 to 19, or 20 to 25,   wherein the binding agent comprises a heavy chain variable region and a light chain variable region,   wherein the heavy chain variable region comprises a first set of the murine CDRs, the first set comprising:
 a first heavy chain CDR (CDRH1), wherein CDRH1 is SEQ ID NO: 11; 
 a second heavy chain CDR (CDRH2), wherein CDRH2 is SEQ ID NO: 12; and 
 a third heavy chain CDR (CDRH3), wherein CDRH3 is SEQ ID NO: 13, 
   wherein the light chain variable region comprises a second set of the murine CDRs, the second set comprising:
 a first light chain CDR (CDRL1), wherein CDRL1 SEQ ID NO: 8; 
 a second light chain CDR (CDRL2), wherein CDRL2 SEQ ID NO: 9; and 
   a third light chain CDR (CDRL3), wherein CDRL3 SEQ ID NO: 10; and   ruling in a bacterial infection for the subject if the polypeptide concentration of HNL determined is higher than a predetermined first threshold value or ruling in a viral infection for the subject if the polypeptide concentration of HNL determined is lower than a predetermined first threshold value.   
     
     
         8 . The method according to  claim 7 ,
 wherein the binding agent has a heavy chain comprising the first set,   wherein the heavy chain comprises a heavy chain variable region sequence selected from the group consisting of sequences depicted in SEQ ID NO: 3,   wherein the binding agent has a light chain comprising the second set,   wherein the light chain comprises a light chain variable region sequence selected from the group consisting of sequences depicted in SEQ ID NO: 2.   
     
     
         9 . A method of distinguishing between a bacterial or mixed infection, and a viral infection in a subject comprising:
 measuring a polypeptide concentration of HNL using a binding agent,   wherein the binding agent is configured to specifically bind to a polypeptide epitope of human neutrophil lipocalin (HNL) with a binding affinity,   wherein the binding agent comprises six murine complementarity-determining regions (CDRs),   wherein each of the CDRs are configured to bind to amino acids 141 to 156 of the human polypeptide epitope of HNL as defined in SEQ ID NO: 1,   wherein the HNL epitope is specifically bound,   wherein the binding affinity is at least 75% or higher compared with a binding specificity achieved with the CDRs, wherein the CDRs are depicted in SEQ ID Nos: 8 to 13, 14 to 19, or 20 to 25,   wherein the binding agent comprises a heavy chain variable region and a light chain variable region,   wherein the heavy chain variable region comprises a first set of the murine CDRs, the first set comprising:
 a first heavy chain CDR (CDRH1), wherein CDRH1 is SEQ ID NO: 11; 
 a second heavy chain CDR (CDRH2), wherein CDRH2 is SEQ ID NO: 12; and 
 a third heavy chain CDR (CDRH3), wherein CDRH3 is SEQ ID NO: 13, 
   wherein the light chain variable region comprises a second set of the murine CDRs, the second set comprising:
 a first light chain CDR (CDRL1), wherein CDRL1 SEQ ID NO: 8; 
 a second light chain CDR (CDRL2), wherein CDRL2 SEQ ID NO: 9; and 
   a third light chain CDR (CDRL3), wherein CDRL3 SEQ ID NO: 10;   measuring a polypeptide concentration of HNL and of CRP in a blood, plasma, serum, urine, CSF, bone marrow, saliva, or sputum sample obtained from a subject;   applying a predetermined mathematical function on the concentrations of HNL and CRP to compute a score; and   comparing the score to a predetermined reference value.   
     
     
         10 . The method according to  claim 9 ,
 wherein the binding agent has a heavy chain comprising the first set,   wherein the heavy chain comprises a heavy chain variable region sequence selected from the group consisting of sequences depicted in SEQ ID NO: 3,   wherein the binding agent has a light chain comprising the second set,   wherein the light chain comprises a light chain variable region sequence selected from the group consisting of sequences depicted in SEQ ID NO: 2.   
     
     
         11 . A method of providing a treatment recommendation for a subject comprising:
 measuring a polypeptide concentration of HNL in a blood, plasma, serum, urine, CSF, bone marrow, saliva, or sputum sample obtained from a subject using a binding agent,   wherein the binding agent is configured to specifically bind to a polypeptide epitope of human neutrophil lipocalin (HNL) with a binding affinity,   wherein the binding agent comprises six murine complementarity-determining regions (CDRs),   wherein each of the CDRs are configured to bind to amino acids 141 to 156 of the human polypeptide epitope of HNL as defined in SEQ ID NO: 1,   wherein the HNL epitope is specifically bound,   wherein the binding affinity is at least 75% or higher compared with a binding specificity achieved with the CDRs, wherein the CDRs are depicted in SEQ ID Nos: 8 to 13, 14 to 19, or 20 to 25,   wherein the binding agent comprises a heavy chain variable region and a light chain variable region,   wherein the heavy chain variable region comprises a first set of the murine CDRs, the first set comprising:
 a first heavy chain CDR (CDRH1), wherein CDRH1 is SEQ ID NO: 11; 
 a second heavy chain CDR (CDRH2), wherein CDRH2 is SEQ ID NO: 12; and 
 a third heavy chain CDR (CDRH3), wherein CDRH3 is SEQ ID NO: 13, 
   wherein the light chain variable region comprises a second set of the murine CDRs, the second set comprising:
 a first light chain CDR (CDRL1), wherein CDRL1 SEQ ID NO: 8; 
 a second light chain CDR (CDRL2), wherein CDRL2 SEQ ID NO: 9; and 
   a third light chain CDR (CDRL3), wherein CDRL3 SEQ ID NO: 10;   recommending that the subject receives an antibiotic treatment if the polypeptide concentration of HNL measured is higher than a predetermined threshold value; and   recommending that the patient does not receive an antibiotic treatment if the polypeptide concentration of HNL measured is lower than a predetermined threshold value or recommending that the patient receive an anti-viral treatment if the polypeptide concentration of HNL measured is lower than a predetermined threshold value.   
     
     
         12 . The method according to  claim 11 ,
 wherein the binding agent has a heavy chain comprising the first set,   wherein the heavy chain comprises a heavy chain variable region sequence selected from the group consisting of sequences depicted in SEQ ID NO: 3,   wherein the binding agent has a light chain comprising the second set,   wherein the light chain comprises a light chain variable region sequence selected from the group consisting of sequences depicted in SEQ ID NO: 2.   
     
     
         13 . A method of providing a diagnostic test recommendation for a subject comprising:
 measuring a polypeptide concentration of HNL in a blood, plasma, serum, urine, CSF, bone marrow, saliva, or sputum sample obtained from a subject using a binding agent   wherein the binding agent is configured to specifically bind to a polypeptide epitope of human neutrophil lipocalin (HNL) with a binding affinity,   wherein the binding agent comprises six murine complementarity-determining regions (CDRs),   wherein each of the CDRs are configured to bind to amino acids 141 to 156 of the human polypeptide epitope of HNL as defined in SEQ ID NO: 1,   wherein the HNL epitope is specifically bound,   wherein the binding affinity is at least 75% or higher compared with a binding specificity achieved with the CDRs, wherein the CDRs are depicted in SEQ ID Nos: 8 to 13, 14 to 19, or 20 to 25,   wherein the binding agent comprises a heavy chain variable region and a light chain variable region,   wherein the heavy chain variable region comprises a first set of the murine CDRs, the first set comprising:
 a first heavy chain CDR (CDRH1), wherein CDRH1 is SEQ ID NO: 11; 
 a second heavy chain CDR (CDRH2), wherein CDRH2 is SEQ ID NO: 12; and 
 a third heavy chain CDR (CDRH3), wherein CDRH3 is SEQ ID NO: 13, 
   wherein the light chain variable region comprises a second set of the murine CDRs, the second set comprising:
 a first light chain CDR (CDRL1), wherein CDRL1 SEQ ID NO: 8; 
 a second light chain CDR (CDRL2), wherein CDRL2 SEQ ID NO: 9; and 
   a third light chain CDR (CDRL3), wherein CDRL3 SEQ ID NO: 10; and   recommending testing the sample for the presence of bacteria if the polypeptide concentration of HNL measured is higher than a predetermined threshold value or recommending testing the sample for the presence of a virus if the polypeptide concentration of HNL measured is lower than a predetermined threshold value.   
     
     
         14 . The method of  claim 13 , further comprising:
 measuring a polypeptide concentration of TRAIL in a blood, plasma, serum, urine, CSF, bone marrow, saliva, or sputum sample obtained from a subject; and   recommending testing the sample for the presence of bacteria if the polypeptide concentration of HNL measured is higher than a predetermined threshold value and if the concentration of TRAIL measured is lower than a predetermined threshold value or testing the sample for the presence of a virus if the polypeptide concentration of HNL measured is lower than a predetermined threshold value and if the polypeptide concentration of TRAIL measured is higher than a predetermined threshold value.   
     
     
         15 . The method according to  claim 13 ,
 wherein the binding agent has a heavy chain comprising the first set,   wherein the heavy chain comprises a heavy chain variable region sequence selected from the group consisting of sequences depicted in SEQ ID NO: 3,   wherein the binding agent has a light chain comprising the second set,   wherein the light chain comprises a light chain variable region sequence selected from the group consisting of sequences depicted in SEQ ID NO: 2.   
     
     
         16 . A method of ruling out a disease in a subject comprising:
 measuring a polypeptide concentration of HNL using a binding agent,   wherein the binding agent is configured to specifically bind to a polypeptide epitope of human neutrophil lipocalin (HNL) with a binding affinity,   wherein the binding agent comprises six murine complementarity-determining regions (CDRs),   wherein each of the CDRs are configured to bind to amino acids 141 to 156 of the human polypeptide epitope of HNL as defined in SEQ ID NO: 1,   wherein the HNL epitope is specifically bound,   wherein the binding affinity is at least 75% or higher compared with a binding specificity achieved with the CDRs, wherein the CDRs are depicted in SEQ ID Nos: 8 to 13, 14 to 19, or 20 to 25,   wherein the binding agent comprises a heavy chain variable region and a light chain variable region,   wherein the heavy chain variable region comprises a first set of the murine CDRs, the first set comprising:
 a first heavy chain CDR (CDRH1), wherein CDRH1 is SEQ ID NO: 11; 
 a second heavy chain CDR (CDRH2), wherein CDRH2 is SEQ ID NO: 12; and 
 a third heavy chain CDR (CDRH3), wherein CDRH3 is SEQ ID NO: 13, 
   wherein the light chain variable region comprises a second set of the murine CDRs, the second set comprising:
 a first light chain CDR (CDRL1), wherein CDRL1 SEQ ID NO: 8; 
 a second light chain CDR (CDRL2), wherein CDRL2 SEQ ID NO: 9; and 
   a third light chain CDR (CDRL3), wherein CDRL3 SEQ ID NO: 10;   measuring a polypeptide concentration of one or more polypeptides selected from the group consisting of TRAIL, IP10, ILIRa or Mac-2BP in a blood, plasma, serum, urine, CSF, bone marrow, saliva, or sputum sample obtained from a subject;   applying a predetermined mathematical function on the concentrations of the polypeptides measured to compute a score; and   comparing the score to a predetermined reference value.   
     
     
         17 . The method according to  claim 16 ,
 wherein the binding agent has a heavy chain comprising the first set,   wherein the heavy chain comprises a heavy chain variable region sequence selected from the group consisting of sequences depicted in SEQ ID NO: 3,   wherein the binding agent has a light chain comprising the second set,   wherein the light chain comprises a light chain variable region sequence selected from the group consisting of sequences depicted in SEQ ID NO: 2.   
     
     
         18 . A method of identifying the type of an infection in a subject comprising:
 measuring a polypeptide concentration of HNL using a binding agent,   wherein the binding agent is configured to specifically bind to a polypeptide epitope of human neutrophil lipocalin (HNL) with a binding affinity,   wherein the binding agent comprises six murine complementarity-determining regions (CDRs),   wherein each of the CDRs are configured to bind to amino acids 141 to 156 of the human polypeptide epitope of HNL as defined in SEQ ID NO: 1,   wherein the HNL epitope is specifically bound,   wherein the binding affinity is at least 75% or higher compared with a binding specificity achieved with the CDRs, wherein the CDRs are depicted in SEQ ID Nos: 8 to 13, 14 to 19, or 20 to 25,   wherein the binding agent comprises a heavy chain variable region and a light chain variable region,   wherein the heavy chain variable region comprises a first set of the murine CDRs, the first set comprising:
 a first heavy chain CDR (CDRH1), wherein CDRH1 is SEQ ID NO: 11; 
 a second heavy chain CDR (CDRH2), wherein CDRH2 is SEQ ID NO: 12; and 
 a third heavy chain CDR (CDRH3), wherein CDRH3 is SEQ ID NO: 13, 
   wherein the light chain variable region comprises a second set of the murine CDRs, the second set comprising:
 a first light chain CDR (CDRL1), wherein CDRL1 SEQ ID NO: 8; 
 a second light chain CDR (CDRL2), wherein CDRL2 SEQ ID NO: 9; and 
   a third light chain CDR (CDRL3), wherein CDRL3 SEQ ID NO: 10;   measuring levels of a first polypeptide determinant selected from the group consisting of TRAIL, IL1RA, IP10, Mac-2BP, B2M, BCA-1, CHI3L1, Eotaxin, IL1a, MCP, CD62L, VEGFR2, CHP, CMPK2, CORO1C, EIF2AK2, ISG15, RPL22L1, RTN3, CD112, CD134, CD182, CD231, CD235A, CD335, CD337, CD45, CD49D, CD66A/C/D/E, CD73, CD84, EGFR, GPR162, HLA-A/B/C, ITGAM, NRG1, RAP1B, SELI, SPINT2, SSEA1, IgG non-specific bound molecules, IL1, I-TAC and TNFR1 in a blood, plasma, serum, urine, CSF, bone marrow, saliva, or sputum sample obtained from a subject; and   measuring levels of a second determinant selected from the group consisting of the polypeptide determinants TRAIL, IL1RA, IP10, Mac-2BP, B2M, BCA-1, CHI3L1, Eotaxin, IL1a, MCP, CD62L, VEGFR2, CHP, CMPK2, CORO1C, EIF2AK2, ISG15, RPL22L1, RTN3, CD112, CD134, CD182, CD231, CD235A, CD335, CD337, CD45, CD49D, CD66A/C/D/E, CD73, CD84, EGFR, GPR162, HLAA/B/C, ITGAM, NRG1, RAP1B, SELI, SPINT2, SSEA1, IgG nonspecific bound molecules, IL1, I-TAC and TNFR1,   the polypeptide determinants IFITM3, IFIT3, EIF4B, IFIT1, LOC26010, MBOAT2, MX1, OAS2, RSAD2, ADIPOR1, CD15, CD8A, IFITM1, and IL7,   the polypeptide determinants CRP, SAA, TREM-1, PCT, IL-8, TREM-1 and IL6, and   the non-polypeptide determinants Age, absolute neutrophil count (ANC), absolute lymphocyte count (ALC), neutrophil % (Neu (%)), lymphocyte % (Lym (%)), monocyte % (Mono (%)), Maximal temperature, Time from symptoms, Creatinine (Cr), Potassium (K), Pulse and Urea;   comparing the levels of HNL, the first polypeptide determinant, and the second determinant to respective reference values thereby identifying the type of infection in the subject,   wherein the measurement of the first polypeptide determinant and the second determinant increases the accuracy of the identification of the type of infection over the measurement of HNL alone.   
     
     
         19 . The method according to  claim 18 ,
 wherein the binding agent has a heavy chain comprising the first set,   wherein the heavy chain comprises a heavy chain variable region sequence selected from the group consisting of sequences depicted in SEQ ID NO: 3,   wherein the binding agent has a light chain comprising the second set,   wherein the light chain comprises a light chain variable region sequence selected from the group consisting of sequences depicted in SEQ ID NO: 2.   
     
     
         20 . A method of identifying the type of an infection in a subject comprising:
 measuring a polypeptide concentration of HNL using a binding agent,   wherein the binding agent is configured to specifically bind to a polypeptide epitope of human neutrophil lipocalin (HNL) with a binding affinity,   wherein the binding agent comprises six murine complementarity-determining regions (CDRs),   wherein each of the CDRs are configured to bind to amino acids 141 to 156 of the human polypeptide epitope of HNL as defined in SEQ ID NO: 1,   wherein the HNL epitope is specifically bound,   wherein the binding affinity is at least 75% or higher compared with a binding specificity achieved with the CDRs, wherein the CDRs are depicted in SEQ ID Nos: 8 to 13, 14 to 19, or 20 to 25,   wherein the binding agent comprises a heavy chain variable region and a light chain variable region,   wherein the heavy chain variable region comprises a first set of the murine CDRs, the first set comprising:
 a first heavy chain CDR (CDRH1), wherein CDRH1 is SEQ ID NO: 11; 
 a second heavy chain CDR (CDRH2), wherein CDRH2 is SEQ ID NO: 12; and 
 a third heavy chain CDR (CDRH3), wherein CDRH3 is SEQ ID NO: 13, 
   wherein the light chain variable region comprises a second set of the murine CDRs, the second set comprising:
 a first light chain CDR (CDRL1), wherein CDRL1 SEQ ID NO: 8; 
 a second light chain CDR (CDRL2), wherein CDRL2 SEQ ID NO: 9; and 
   a third light chain CDR (CDRL3), wherein CDRL3 SEQ ID NO: 10;   measuring levels of one or more polypeptide determinants selected from the group consisting of ABTB1, ADIPOR1, ARHGDIB, ARPC2, ATP6V0B, Clorf83, CD15, CES1, CORO1A, CSDA, EIF4B, EPSTI1, GAS 7, HERC5, IFI6, KIAA0082, IFIT1, IFIT3, IFITM1, IFITM3, LIPT1, IL7R, ISG20, LOC26010, LY6E, LRDD, LTA4H, MAN1C1, MBOAT2, NPM1, OAS2, PARP12, PARP9, QARS, RAB13, RAB31, RAC2, RPL34, PDIA6, PTEN, RSAD2, SART3, SDCBP, SMAD9, SOCS3, TRIM22, SART3, UBE2N, XAF1, ZBP1, CRP and MX1 in a blood, plasma, serum, urine, CSF, bone marrow, saliva, or sputum sample obtained from a subject; and   comparing the levels of HNL and of the one or more polypeptide determinants to a reference value thereby identifying the type of infection in the subject.   
     
     
         21 . The method of  claim 20 , further comprising measuring one or more non-polypeptide determinants, selected from the group consisting of Age, absolute neutrophil count (ANC), absolute lymphocyte count (ALC), neutrophil % (Neu (%)), lymphocyte % (Lym (%)), monocyte % (Mono (%)), Maximal temperature, Time from symptoms, Creatinine (Cr), Potassium (K), Pulse and Urea. 
     
     
         22 . The method according to  claim 20 ,
 wherein the binding agent has a heavy chain comprising the first set,   wherein the heavy chain comprises a heavy chain variable region sequence selected from the group consisting of sequences depicted in SEQ ID NO: 3,   wherein the binding agent has a light chain comprising the second set,   wherein the light chain comprises a light chain variable region sequence selected from the group consisting of sequences depicted in SEQ ID NO: 2.   
     
     
         23 . A device for the diagnosis of bacterial infections in a blood, plasma, serum, urine, CSF, bone marrow, saliva, or sputum sample comprising:
 a first compartment,
 wherein the first compartment comprises the binding agent, 
 wherein the binding agent is configured to specifically bind to a polypeptide epitope of human neutrophil lipocalin (HNL) with a binding affinity, 
 wherein the binding agent comprises six murine complementarity-determining regions (CDRs), 
 wherein each of the CDRs are configured to bind to amino acids 141 to 156 of the human polypeptide epitope of HNL as defined in SEQ ID NO: 1, 
 wherein the HNL epitope is specifically bound, 
 wherein the binding affinity is at least 75% or higher compared with a binding specificity achieved with the CDRs, wherein the CDRs are depicted in SEQ ID Nos: 8 to 13, 14 to 19, or 20 to 25, 
 wherein the binding agent comprises a heavy chain variable region and a light chain variable region, 
 wherein the heavy chain variable region comprises a first set of the murine CDRs, the first set comprising: 
 a first heavy chain CDR (CDRH1), wherein CDRH1 is SEQ ID NO: 11; 
 a second heavy chain CDR (CDRH2), wherein CDRH2 is SEQ ID NO: 12; and 
 a third heavy chain CDR (CDRH3), wherein CDRH3 is SEQ ID NO: 13, 
 wherein the light chain variable region comprises a second set of the murine CDRs, the second set comprising: 
 a first light chain CDR (CDRL1), wherein CDRL1 SEQ ID NO: 8; 
 a second light chain CDR (CDRL2), wherein CDRL2 SEQ ID NO: 9; and 
 a third light chain CDR (CDRL3), wherein CDRL3 SEQ ID NO: 10, 
 wherein the first compartment is suitable to be brought into contact with the sample; 
   a second compartment,
 wherein the second compartment comprises a chemical substrate capable of activating neutrophils present in the sample before further analysis, 
 wherein the second compartment comprises an orifice connecting it with the first compartment comprising the binding agent; 
   a connector, wherein the connector is arranged to connect the device with another device for removal of a blood sample from a suspect; and   a connector,
 wherein the connector is arranged to combine the device with a computer and/or an apparatus for the analysis of chemical, physical or biological reactions in the device, 
 wherein the reactions are indicative for an interaction of HNL and the binding agent, 
 wherein the reactions permit determining the level of HNL in the sample. 
   
     
     
         24 . The device of  claim 23 , further comprising a binding agent for one or more additional polypeptide determinants selected from the group consisting of ABTB1, ADIPOR1, ARHGDIB, ARPC2, ATP6V0B, Clorf83, CD15, CES1, CORO1A, CSDA, EIF4B, EPSTI1, GAS 7, HERC5, IFI6, KIAA0082, IFIT1, IFIT3, IFITM1, IFITM3, LIPT1, IL7R, ISG20, LOC26010, LY6E, LRDD, LTA4H, MAN1C1, MBOAT2, NPM1, OAS2, PARP12, PARP9, QARS, RAB13, RAB31, RAC2, RPL34, PDIA6, PTEN, RSAD2, SART3, SDCBP, SMAD9, SOCS3, TRIM22, SART3, UBE2N, XAF1, ZBP1, CRP and MX1,
 wherein the reactions are indicative for an interaction of the polypeptide determinants, and the level of the polypeptide determinants in the sample,   wherein the device is selected from the group consisting of point-of-care devices, test strips, radioimmunoassays, ELISA, “sandwich” immunoassays, immunoradiometric assays, gel diffusion precipitation assays, immunodiffusion assays, in situ immunoassays using colloidal gold, enzyme or radioisotope labels, Western blots, precipitation assays, gel agglutination assays, hemagglutination assays, immunofluorescence assays, protein A assays, immunoelectrophoresis assays, and devices for detection of analytes that involve magnetic based separation of the analytes.   
     
     
         25 . The device according to  claim 23 ,
 wherein the binding agent has a heavy chain comprising the first set,   wherein the heavy chain comprises a heavy chain variable region sequence selected from the group consisting of sequences depicted in SEQ ID NO: 3,   wherein the binding agent has a light chain comprising the second set,   wherein the light chain comprises a light chain variable region sequence selected from the group consisting of sequences depicted in SEQ ID NO: 2.   
     
     
         26 . A binding agent comprising:
 six complementarity-determining regions (CDRs);   a heavy chain comprising three of the CDRs and a murine sequence selected from the group consisting of sequences depicted in SEQ ID NOs: 3, 5, and 7; and   a light chain,   wherein the binding agent is configured to specifically bind to a polypeptide epitope of HNL comprising amino acids 141 to 156 of HNL as defined in the human peptide sequence of SEQ ID NO: 1 with a defined binding affinity,   wherein the binding agent is configured to specifically bind to a polypeptide epitope of HNL with a defined binding affinity,   wherein the light chain comprises a set of CDRs, the set comprising:
 a CDRL1 depicted in SEQ ID NO: 8; 
 a CDRL2 selected from depicted in—SEQ ID NO: 9; and 
 a CDRL3 depicted in SEQ ID NO: 10, 
   wherein L denotes a light chain variable region,   wherein the defined binding affinity as measured by K D  for HNL is in the range of 1×10 −6  M or less.   
     
     
         27 . A derivative of a binding agent of  claim 26 , wherein the binding agent is covalently modified by conjugation to a diagnostic agent, labeling with a radionuclide, labeling with an enzyme, or covalently attaching a polymer. 
     
     
         28 . A binding agent comprising:
 six complementarity-determining regions (CDRs);   a light chain comprising three of the CDRs and a murine sequence selected from the group consisting of sequences depicted in SEQ ID NOs: 2, 4, and 6; and   a heavy chain,   wherein the binding agent is configured to specifically bind to a polypeptide epitope of HNL comprising amino acids 141 to 156 of HNL as defined in the human peptide sequence of SEQ ID NO: 1 with a defined binding affinity,   wherein the heavy chain comprises a set of CDRs, the set comprising:
 a CDRH1 depicted in SEQ ID NO: 11; 
 a CDRH2 depicted in SEQ ID NO: 12; and 
 a CDRH3 depicted in SEQ ID NO: 13, 
 wherein H denotes a heavy chain variable region, 
   wherein the defined binding affinity as measured by K D  for HNL is in the range of 1×10 −6  M or less.   
     
     
         28 . A derivative of a binding agent of  claim 27 , wherein the binding agent is covalently modified by conjugation to a diagnostic agent, labeling with a radionuclide, labeling with an enzyme, or covalently attaching a polymer. 
     
     
         29 . A binding agent comprising:
 a heavy chain comprising a first set of murine complementarity-determining regions (CDRs), the first set comprising:
 a CDRH1 depicted in SEQ ID NO: 11; 
 a CDRH2 depicted in SEQ ID NO: 12; and 
 a CDRH3 depicted in SEQ ID NO: 13, 
 where H denotes a heavy chain variable region; 
   a light chain comprising a second set of murine CDRs, the second set comprising:
 a CDRL1 depicted in SEQ ID NO: 8; 
 a CDRL2 depicted in SEQ ID NO: 9; and 
 a CDRL3 depicted in SEQ ID NO: 10, 
 where L denotes a light chain variable region; or 
   a combination of heavy and/or light chains,   wherein the binding agent is configured to specifically bind to a polypeptide epitope of human neutrophil lipocalin (HNL) comprising amino acids 141 to 156 of HNL as defined in the human peptide sequence of SEQ ID NO: 1 with a defined binding affinity,   wherein the binding agent is configured to specifically bind to a polypeptide epitope of HNL with a defined binding affinity,   wherein the defined binding affinity as measured by K D  for HNL is in the range of 1×10 −6  M or less.   
     
     
         30 . The binding agent according to  claim 29 , wherein the binding agent is a monoclonal antibody, a chimeric antibody, or a humanized antibody. 
     
     
         31 . A derivative of a binding agent of  claim 29 , wherein the binding agent is covalently modified by conjugation to a diagnostic agent, labeling with a radionuclide, labeling with an enzyme, or covalently attaching a polymer.