Uses of carbamoyl phosphate synthetase for the diagnois of inflammatory diseases and sepsis
Use of carbamoyl phosphate synthetase 1 (CPS 1) and/or of fragments of the N-terminal part of CPS 1 from body fluids or body tissues as marker peptides for the diagnosis and for the prognosis and the monitoring of inflammations and infections, including sepsis, and of liver failure as part of multiorgan failure or for determinations in connection with inflammatory and other liver diseases.
1. A method for the diagnosis of sepsis in a human patient comprising:
(a) obtaining a blood, plasma, or serum sample from said patient; and
determining the presence and amount of human carbamoyl phosphate synthetase 1 (CPS 1) (SEQ ID NO: 6) in said sample using an immunodiagnostic assay.
2. The method of claim 1 , further comprising detennining the presence and amount of:
(a) human CPS 1 (SEQ ID NO:6) having an apparent molecular weight of 200 kDa +/−50 kDa using gel filtration and HPLC;
fragments of human CPS 1 (SEQ ID NO:6) having an apparent molecular weight of 68 to 70 kDa+/−3kDa; and isoelectric points in the range from 5.5 to 6.1 in said sample using two-dimensional gel electrophoresis.
3. The method of claim 1 , wherein the immunodiagnostic assay is a sandwich assay.
4. The method according to claim 1 , wherein said method comprises using one or more antibody that specifically recognizes the N-terminal portion of human CPS 1 consisting of amino acids 1-630 of SEQ ID NO:6.
5. The method according to claim 4 , wherein the one or more antibody binds a sequence chosen from SEQ ID NO.: 1, SEQ ID NO.:2, SEQ ID NO.:3, SEQ ID NO.:4, SEQ ID NO.:5, SEQ ID NO.:7 and SEQ ID NO.:8.
6. The method of claim 5 , wherein the antibodies are produced from a protein chosen from SEQ ID NO:7 and SEQ ID NO:8.
7. The method according to claim 1 , wherein step (b) alternatively comprises: performing a multi-parameter determination, wherein the presence and amount of human carbamoyl phosphate synthetase 1 (CPS 1) (SEQ ID NO:6) is co-determined with at least one other sepsis marker.
8. The method according to claim 7 , wherein the at least one other sepsis marker is chosen from procalcitonin, cancer antigen 19-9 (CA 19-9), cancer antigen 125 (CA 125), protein S100B, protein S100 A, soluble cytokeratin fragments, inflammin peptide, calcitonin-homologue peptide (CHP), the LIM, actin, and SH3 domain protein-1 (LASP-1), peptide prohormone immunoreactivity, and C-reactive protein (CRP).
9. The method of claim 8 , wherein the soluble cytokeratin fragments are chosen from soluble cytokeratin-19 fragments (CYFRA 21), a soluble cytokeratin-18 fragment known as polypeptide specific antigen (TPS), and soluble cytokeratin-1 fragments (sCY1 F).
10. The method according to claim 7 , wherein the multi-parameter determination is carried out as a simultaneous determination by means of a chip technology measuring device or of an immunochromatographic measuring device.
11. The method according to claim 10 , wherein said measuring device provides a complex measured result that is evaluated with the aid of a computer program.
12. The method of claim 1 further comprising determining the severity of sepsis on the basis of the concentration of CPS 1, wherein the greater the concentration of CPS 1, the greater the severity of sepsis.