Establishment of an ELISA for the Recognition of Procalcitonin Variants in Patients With Hyperprocalcitonemia.
Study Details
Study Description
Brief Summary
Procalcitonin is a protein consisting of 116 amino-acids which can rapidly rise under inflammatory conditions and sepsis. More than 20 years ago it has been shown that dipeptidylpeptidase-4 (DPP-4) cleaves procalcitonin from the n-terminus, resulting in a truncated procalcitonin-variant which consists of 114 aminoacids. Within our workgroup we found that the truncated procalcitonin-variant had deleterious effects on vascular integrity during sepsis in mice. However, it is unknown if this applies also in humans. By using an ELISA-assay we want to examine the ratio between native and truncated human procalcitonin during diseases accompanied with hyperprocalcitoninemia and correlate the results with clinical data.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
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Detailed Description
Procalcitonin is a protein consisting of 116 amino-acids which can rapidly rise under inflammatory conditions and sepsis. More than 20 years ago it has been shown that dipeptidylpeptidase-4 (DPP-4) cleaves procalcitonin from the n-terminus, resulting in a truncated procalcitonin-variant which consists of 114 aminoacids.
Within our workgroup we found that the truncated procalcitonin-variant had deleterious effects on vascular integrity during sepsis in mice: We observed that binding of truncated procalcitonin to the CRLR/RAMP1-receptor on vascular endothelium lead to phosphorylation and destruction of VE-cadherin, an essential part of adherens junctions. Consequently, paracellular leakage of proteins and fluid from blood vessels developed.
It is unknown if these effects also apply to humans. By using an ELISA-assay we want to examine the ratio between native and truncated human procalcitonin during diseases accompanied with hyperprocalcitoninemia and correlate the results with clinical data. Futhermore, we want to examine if the procalcitonin-variants have influence on cytokine levels and surface antigens on immune cells by performing multiplex immunoassays and FACS-analysis.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Sepsis Withdrawal of 3 blood collection tubes for ELISA-measurements at a single time during hyperprocalcitoninemia. |
Diagnostic Test: Procalcitonin-variants ELISA-Assay
Observational study measuring procalcitonin-variants in different patient collectives by obtaining 3 blood collection tubes per patient.
|
| SIRS Withdrawal of 3 blood collection tubes for ELISA-measurements at a single time during hyperprocalcitoninemia. |
Diagnostic Test: Procalcitonin-variants ELISA-Assay
Observational study measuring procalcitonin-variants in different patient collectives by obtaining 3 blood collection tubes per patient.
|
| Adiposity Withdrawal of 3 blood collection tubes for ELISA-measurements at a single time during hyperprocalcitoninemia. |
Diagnostic Test: Procalcitonin-variants ELISA-Assay
Observational study measuring procalcitonin-variants in different patient collectives by obtaining 3 blood collection tubes per patient.
|
| Granulomatosis with polyangiitis / microscopic polyangiitis Withdrawal of 3 blood collection tubes for ELISA-measurements at a single time during hyperprocalcitoninemia. |
Diagnostic Test: Procalcitonin-variants ELISA-Assay
Observational study measuring procalcitonin-variants in different patient collectives by obtaining 3 blood collection tubes per patient.
|
| Pre-eclampsia Withdrawal of 3 blood collection tubes for ELISA-measurements at a single time during hyperprocalcitoninemia. |
Diagnostic Test: Procalcitonin-variants ELISA-Assay
Observational study measuring procalcitonin-variants in different patient collectives by obtaining 3 blood collection tubes per patient.
|
| Healthy controls Withdrawal of 3 blood collection tubes for ELISA-measurements at a single time during hyperprocalcitoninemia. |
Diagnostic Test: Procalcitonin-variants ELISA-Assay
Observational study measuring procalcitonin-variants in different patient collectives by obtaining 3 blood collection tubes per patient.
|
Outcome Measures
Primary Outcome Measures
- Ratio between native and truncated procalcitonin during different conditions of hyperprocalcitoninemia [Blood withdrawal takes approximately 5 minutes per patient]
Measurement performed by using ELISA-assay.
Secondary Outcome Measures
- DPP-4-activity [Blood withdrawal takes approximately 5 minutes per patient]
Measurement performed by using a commercial DPP4-ELISA-kit.
- Proinflammatory cytokines [Blood withdrawal takes approximately 5 minutes per patient]
Measurement performed by using a commercial multiplex immunoassay kit.
- Immun cell surface-antigens [Blood withdrawal takes approximately 5 minutes per patient]
Measurement performed by using fluorescence-acivated cell sorting (FACS).
Eligibility Criteria
Criteria
Inclusion Criteria:
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Age >18
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Patients with diagnosis...
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Sepsis or,
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SIRS after cardiothoracic surgery or,
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adipositas or,
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granulomatosis with polyangiitis/microscopic polyangiitis or,
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pre-eclampsia
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healthy control subjects
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written informed consent
Exclusion Criteria:
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participation in an interventional study trial within the last 3 months
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relationship to study investigator
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University Hospital Münster | Münster | North Rhine-Westphalia | Germany | 48147 |
Sponsors and Collaborators
- University Hospital Muenster
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
- Brabenec L, Muller M, Hellenthal KEM, Karsten OS, Pryvalov H, Otto M, Holthenrich A, Matos ALL, Weiss R, Kintrup S, Hessler M, Dell'Aquila A, Thomas K, Nass J, Margraf A, Nottebaum AF, Rossaint J, Zarbock A, Vestweber D, Gerke V, Wagner NM. Targeting Procalcitonin Protects Vascular Barrier Integrity. Am J Respir Crit Care Med. 2022 Aug 15;206(4):488-500. doi: 10.1164/rccm.202201-0054OC.
- Wrenger S, Kahne T, Bohuon C, Weglohner W, Ansorge S, Reinhold D. Amino-terminal truncation of procalcitonin, a marker for systemic bacterial infections, by dipeptidyl peptidase IV (DP IV). FEBS Lett. 2000 Jan 21;466(1):155-9. doi: 10.1016/s0014-5793(99)01779-2.
- 10-AnIt-19