Method and substances for diagnosis and therapy of sepsis and sepsis-like systemic infections

• US 20040180396A1
• Filed: 03/25/2004
• Published: 09/16/2004
• Est. Priority Date: 10/15/1998
• Status: Active Grant

• Current Assignee: B·R·A·H·M·S GmbH (Thermo Fisher Scientific Incorporated)
• Original Assignee: B.R.A.H.M.S Aktiengesellschaft
• Inventors: Struck, Joachim, Bergmann, Andreas, Weglohner, Wolfgang
• Granted Patent: US 7,498,139 B2
• Time in Patent Office: Days
• US Class Current: 435/23
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: C07K 14/585 Calcitonins
• CPC Class Codes: G01N 2333/585 Calcitonins
• CPC Class Codes: G01N 33/74 involving hormones or other non-cytokine intercellular protein regulatory factors such as growth factors, including receptors to hormones and growth factors

Abstract

Uses of recombinant procalcitonin 3-116 in the diagnosis and therapy of septic diseases and the measurement of prohormones other than procalcitonin, and of dipeptidyl peptidase IV, as biomarkers in the diagnosis of sepsis.

Claims

1. Method for the differential-diagnostic early detection and detection, for the assessment of the severity, and for the assessment of the success of a therapeutic treatment of sepsis and severe infections, in particular sepsis-like systematic infections, characterized in that the content of at least one peptide prohormone other than procalcitonin and/or of a partial peptide derived therefrom, which is not the mature hormone obtainable from said peptide prohormone, is determined in a sample of a biological fluid of a patient, and the presence of a sepsis or sepsis-like systematic infection, its severity and/or the success of a therapeutic treatment are determined from the detected presence and/or amount of the determined peptide prohormone.

2. Method according to claim 1, characterized in that the peptide prohormone is selected from the group consisting of a pro-gastric-releasing peptide (proGRP), pro-endothelin-1(pro-END), pro-brain-natriuretic peptide (pro-BNP), pro-atrial-natriuretic peptide (pro-ANP or pro-ANF), pro-leptin, pro-neuropeptide-Y, pro-somatostatin, pro-neuropeptide-YY or pro-adrenomedullin (pro-ADM).

3. Method according to claim 1, characterized in that by the determination a partial peptide is detected which differs from the known complete peptide prohormone by the lack of a dipeptide at the amino terminus thereof, as it can be cleaved off by dipeptidyl-aminopeptidase IV (DP IV or DAP IV or CD26) from the end of a peptide.

4. Method according to claim 3, characterized in that the dipeptide is an Xaa-Pro dipeptide, Xaa representing the amino-terminal amino acid of the complete prohormone peptide.

5. Method according to claim 1, characterized in that said determination of said peptide prohormone is carried out as an immunoassay or precipitation assay, and a diagnosis of the presence of sepsis or severe sepsis-like infections is made if the concentration of the peptide prohormone determined is significantly higher than the values for the same prohormone observed in healthy normal persons.

7. Method according to claim 2, characterized in that by the determination a partial peptide is detected which differs from the known complete peptide prohormone by the lack of a dipeptide at the amino terminus thereof, as it can be cleaved off by dipeptidyl-aminopeptidase IV (DP IV or DAP IV or CD26) from the end of a peptide.

6. Method for the differential-diagnostic early detection, for the detection, and for the assessment of the severity and for the assessment of the success of a therapeutic treatment of a sepsis and sepsis-like systematic infections, characterized in that the content of dipeptidyl-pepidase IV (DP IV;

dipeptidyl-aminopeptidase IV;

DAP IV or CD26) is determined in a serum or plasma sample of a patient and the presence of a sepsis or sepsis-like systematic infection is diagnosed on the basis of a concentration of dipeptidyl-peptidase IV which is significantly reduced compared with healthy normal subjects.