Method for early detection, detection of the severity and for a treatment-accompanying assessment of the course of a sepsis

• US 5,639,617 A
• Filed: 02/17/1995
• Issued: 06/17/1997
• Est. Priority Date: 08/19/1992
• Status: Expired due to Term

• Current Assignee: B·R·A·H·M·S GmbH (Thermo Fisher Scientific Incorporated)
• Original Assignee: B.R.A.H.M.S. Diagnostica GmbH (Thermo Fisher Scientific Incorporated)
• Inventors: Bohuon, Claude
• Primary Examiner(s): Housel, James C.
• Assistant Examiner(s): PORTNER, VIRGINIA ALLEN
• Application Number:
  US08/387,714
• Time in Patent Office: 851 Days
• Field of Search: 435/7.1, 435/7.94, 424/139.1, 424/158.1
• US Class Current: 435/7.1
• CPC Class Codes: C07K 14/585 Calcitonins
• CPC Class Codes: C07K 16/26 against hormones ; against hormone releasing or inhibiting factors
• 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

Disclosed is a method for early detection, detection of the severity as well as for a treatment-accompanying assessment of the course of a sepsis as well as means for carrying out said method. According to the invention, the content of the peptide procalcitonin and/or of a partial peptide formed therefrom which is not the mature calcitonin is determined in a sample of a biological liquid of a patient. From the determined presence and amount of the certain peptide, a conclusion is made about the presence of a sepsis, its severity and/or the success of a therapeutic treatment.

Claims

1. Method for early detection of a sepsis in a patient in need thereof comprising:

determining in a sample of a biological liquid of a patient the concentration of procalcitonin, the determined presence and amount of procalcitonin being indicative of the presence of a sepsis.

2. The method according to claim 1, characterized in that procalcitonin and N-procalcitonin (amino acids 1-57)-peptide and C-procalcitonin-(amino acids 60-116)-peptides are determined.

3. Method according to claim 1 or 2, characterized in that the corresponding peptide or peptides are determined in an immunodiagnostic method by use of a monoclonal antibody or a combination of a first monoclonal or polyclonal antibody with a second monoclonal antibody, which as such or combined with each other have a specificity for procalcitonin or peptides formed therefrom, and which allow to differentiate between them and mature calcitonin and the CGRP peptide.

4. Method according to claim 3, characterized in that procalcitonin is determined by means of an immunometric assay wherein for binding the procalcitonin from the sample a first monoclonal antibody is used binding the procalcitonin in another region as the second monoclonal antibody used for marking, so that a differentiation between procalcitonin and its proteolyic degradation products including calcitonin is possible.

5. Method according to claim 4, characterized in that, apart from the first monoclonal antibody, for binding procalcitonin at least one further monoclonal antibody is used which binds the procalcitonin molecule in another region.

6. Method according to claims 1, characterized in that procalcitonin is determined by means of an immunometric assay which selectively detects the complete procalcitonin and C-procalcitonin-(60-116)-peptide, if present.

7. Method according to claim 1, characterized in that procalcitonin is determined by means of an immunometric assay which selectively detects the complete procalcitonin and N-procalcitonin-(1-57)-peptide.

8. Method according to claim 6, characterized in that procalcitonin contents of more than 1 ng/ml sample are indicative of the possible .presence of a sepsis and that procalcitonin contents in the range of 10 ng/ml to 500 ng/ml and higher correlate with an increasing severity of the sepsis and a worsened prognosis.

9. Method according to claim 8, characterized in that simultaneously in a parallel determination the calcitonin level is determined and that the absence of evidence for elevated calcitonin levels allows the sepsis diagnosis to be made.

10. Method according to claim 8 or 9, characterized in that procalcitonin levels in the range of approximately up to 20 ng/ml allow the sepsis diagnosis to be made, if the presence of a serious virus disease as a reason for the elevated procalcitonin level can be excluded.

11. Method according to claim 1, characterized in that a serum or plasma sample is used as the sample of a biological liquid.

12. Method according to claim 1, characterized in that the monoclonal antibody is the monoclonal antibody KC01 (DSM ACC2124) or the antibody CT21 (DSM ACC2125).

13. The method of claim 1 wherein the amount of the peptide detected indicates the severity of the sepsis or the success of a therapeutic treatment.

14. The method of claim 13 wherein the antibody is selected from the group consisting of monoclonal antibodies KC01 and CT21.

15. The method of claim 1, wherein the concentration of procalcitonin is determined immunologically.