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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 their workgroup the investigators 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 the investigators want to examine the ratio between native and truncated human procalcitonin during diseases accompanied with hyperprocalcitoninemia and correlate the results with clinical data.
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 their workgroup the investigators found that the truncated procalcitonin-variant had deleterious effects on vascular integrity during sepsis in mice: They 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 the investigators want to examine the ratio between native and truncated human procalcitonin during diseases accompanied with hyperprocalcitoninemia and correlate the results with clinical data. Futhermore, they 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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Sepsis | Withdrawal of 3 blood collection tubes for ELISA-measurements at a single time during hyperprocalcitoninemia. |
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| SIRS | Withdrawal of 3 blood collection tubes for ELISA-measurements at a single time during hyperprocalcitoninemia. |
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| Adiposity | Withdrawal of 3 blood collection tubes for ELISA-measurements at a single time during hyperprocalcitoninemia. |
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| Granulomatosis with polyangiitis / microscopic polyangiitis | Withdrawal of 3 blood collection tubes for ELISA-measurements at a single time during hyperprocalcitoninemia. |
| |
| Pre-eclampsia | Withdrawal of 3 blood collection tubes for ELISA-measurements at a single time during hyperprocalcitoninemia. |
| |
| Healthy controls |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Procalcitonin-variants ELISA-Assay | Diagnostic Test | Observational study measuring procalcitonin-variants in different patient collectives by obtaining 3 blood collection tubes per patient. |
| Measure | Description | Time Frame |
|---|---|---|
| Ratio between native and truncated procalcitonin during different conditions of hyperprocalcitoninemia | Measurement performed by using ELISA-assay. | Blood withdrawal takes approximately 5 minutes per patient |
| Measure | Description | Time Frame |
|---|---|---|
| DPP-4-activity | Measurement performed by using a commercial DPP4-ELISA-kit. | Blood withdrawal takes approximately 5 minutes per patient |
| Proinflammatory cytokines | Measurement performed by using a commercial multiplex immunoassay kit. |
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Inclusion Criteria:
Exclusion Criteria:
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Patients from the University Hospital Münster who suffer from different diseases which are accompanied by hyperprocalcitoninemia.
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University Hospital Münster | Münster | North Rhine-Westphalia | 48147 | Germany |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 10648832 | Background | 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. | |
| 35699655 | Background | 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. |
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Withdrawal of 3 blood collection tubes for ELISA-measurements at a single time during hyperprocalcitoninemia. |
|
| Blood withdrawal takes approximately 5 minutes per patient |
| Immun cell surface-antigens | Measurement performed by using fluorescence-acivated cell sorting (FACS). | Blood withdrawal takes approximately 5 minutes per patient |
| 11786196 | Result | Weglohner W, Struck J, Fischer-Schulz C, Morgenthaler NG, Otto A, Bohuon C, Bergmann A. Isolation and characterization of serum procalcitonin from patients with sepsis. Peptides. 2001 Dec;22(12):2099-103. doi: 10.1016/s0196-9781(01)00541-1. |
| 39636188 | Derived | Kintrup S, Brabenec L, Zurek-Leffers FM, Hellenthal KEM, Cyran L, Meybohm P, Gerke V, Wagner NM. Detection and Evaluation of Procalcitonin Variants As Diagnostic Tools in Systemic Inflammation. Anesth Analg. 2025 May 1;140(5):1073-1082. doi: 10.1213/ANE.0000000000007170. |
| ID | Term |
|---|---|
| D018805 | Sepsis |
| D011225 | Pre-Eclampsia |
| D014890 | Granulomatosis with Polyangiitis |
| D055953 | Microscopic Polyangiitis |
| D009765 | Obesity |
| ID | Term |
|---|---|
| D007239 | Infections |
| D018746 | Systemic Inflammatory Response Syndrome |
| D007249 | Inflammation |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D046110 | Hypertension, Pregnancy-Induced |
| D011248 | Pregnancy Complications |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D017563 | Lung Diseases, Interstitial |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D056648 | Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis |
| D056647 | Systemic Vasculitis |
| D014657 | Vasculitis |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D017445 | Skin Diseases, Vascular |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |
| D059345 | Cerebral Small Vessel Diseases |
| D002561 | Cerebrovascular Disorders |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D050177 | Overweight |
| D044343 | Overnutrition |
| D009748 | Nutrition Disorders |
| D009750 | Nutritional and Metabolic Diseases |
| D001835 | Body Weight |
| D012816 | Signs and Symptoms |
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