Novel Methods for the Quantification of Dipeptidyl Peptidase 3 (DPP3) Concentration and Activity in Human Blood Samples
Rehfeld, Linda ; Funk, Eugenia ; Jha, Shalinee ; Macheroux, Peter ; Melander, Olle LU
and Bergmann, Andreas
(2019)
In The Journal of Applied Laboratory Medicine
3(6).
p.943-953
- Abstract
BACKGROUND: The ubiquitously expressed dipeptidyl peptidase 3 (DPP3) is involved in protein metabolism, blood pressure regulation, and pain modulation. These diverse functions of DPP3 are attributed to the degradation of bioactive peptides like angiotensin II. However, because of limitations in currently available assays for determination of active DPP3 in plasma, the exact physiological function of DPP3 and its role in the catabolism of bioactive peptides is understudied. Here, we developed 2 assays to specifically detect and quantify DPP3 protein and activity in plasma and validated DPP3 quantification in samples from critically ill patients. METHODS: Assay performance was evaluated in a sandwich-type luminometric immunoassay (LIA)... (More)
BACKGROUND: The ubiquitously expressed dipeptidyl peptidase 3 (DPP3) is involved in protein metabolism, blood pressure regulation, and pain modulation. These diverse functions of DPP3 are attributed to the degradation of bioactive peptides like angiotensin II. However, because of limitations in currently available assays for determination of active DPP3 in plasma, the exact physiological function of DPP3 and its role in the catabolism of bioactive peptides is understudied. Here, we developed 2 assays to specifically detect and quantify DPP3 protein and activity in plasma and validated DPP3 quantification in samples from critically ill patients. METHODS: Assay performance was evaluated in a sandwich-type luminometric immunoassay (LIA) and an enzyme capture activity assay (ECA). DPP3 plasma concentrations and activities were detected in a healthy, population-based cohort and in critically ill patients suffering from severe sepsis and septic shock. RESULTS: The DPP3-LIA and DPP3-ECA show an almost ideal correlation and very similar and robust performance characteristics. DPP3 activity is detectable in plasma of predominantly healthy subjects with a mean (±SD) of 58.6 (±20.5) U/L. Septic patients show significantly increased DPP3 plasma activity at hospital admission. DPP3 activities further increase in patients with more severe conditions and high mortality risk. CONCLUSION: We developed 2 highly specific assays for the detection of DPP3 in plasma. These assays allow the use of DPP3 as a biomarker for the severity of acute clinical conditions and will be of great value for future investigations of DPP3's role in bioactive peptide degradation in general and the angiotensin II pathway in specific.
(Less)
- author
- Rehfeld, Linda
; Funk, Eugenia
; Jha, Shalinee
; Macheroux, Peter
; Melander, Olle
LU
and Bergmann, Andreas
- organization
- publishing date
- 2019
- type
- Contribution to journal
- publication status
- published
- subject
- in
- The Journal of Applied Laboratory Medicine
- volume
- 3
- issue
- 6
- pages
- 11 pages
- publisher
- Oxford University Press
- external identifiers
-
- scopus:85090819169
- pmid:31639686
- ISSN
- 2576-9456
- DOI
- 10.1373/jalm.2018.027995
- language
- English
- LU publication?
- yes
- id
- aaaa00a5-b7fb-4b65-8700-9bceb9aa1604
- date added to LUP
- 2020-10-20 15:21:42
- date last changed
- 2024-06-28 02:42:31
@article{aaaa00a5-b7fb-4b65-8700-9bceb9aa1604,
abstract = {{<p>BACKGROUND: The ubiquitously expressed dipeptidyl peptidase 3 (DPP3) is involved in protein metabolism, blood pressure regulation, and pain modulation. These diverse functions of DPP3 are attributed to the degradation of bioactive peptides like angiotensin II. However, because of limitations in currently available assays for determination of active DPP3 in plasma, the exact physiological function of DPP3 and its role in the catabolism of bioactive peptides is understudied. Here, we developed 2 assays to specifically detect and quantify DPP3 protein and activity in plasma and validated DPP3 quantification in samples from critically ill patients. METHODS: Assay performance was evaluated in a sandwich-type luminometric immunoassay (LIA) and an enzyme capture activity assay (ECA). DPP3 plasma concentrations and activities were detected in a healthy, population-based cohort and in critically ill patients suffering from severe sepsis and septic shock. RESULTS: The DPP3-LIA and DPP3-ECA show an almost ideal correlation and very similar and robust performance characteristics. DPP3 activity is detectable in plasma of predominantly healthy subjects with a mean (±SD) of 58.6 (±20.5) U/L. Septic patients show significantly increased DPP3 plasma activity at hospital admission. DPP3 activities further increase in patients with more severe conditions and high mortality risk. CONCLUSION: We developed 2 highly specific assays for the detection of DPP3 in plasma. These assays allow the use of DPP3 as a biomarker for the severity of acute clinical conditions and will be of great value for future investigations of DPP3's role in bioactive peptide degradation in general and the angiotensin II pathway in specific.</p>}},
author = {{Rehfeld, Linda and Funk, Eugenia and Jha, Shalinee and Macheroux, Peter and Melander, Olle and Bergmann, Andreas}},
issn = {{2576-9456}},
language = {{eng}},
number = {{6}},
pages = {{943--953}},
publisher = {{Oxford University Press}},
series = {{The Journal of Applied Laboratory Medicine}},
title = {{Novel Methods for the Quantification of Dipeptidyl Peptidase 3 (DPP3) Concentration and Activity in Human Blood Samples}},
url = {{http://dx.doi.org/10.1373/jalm.2018.027995}},
doi = {{10.1373/jalm.2018.027995}},
volume = {{3}},
year = {{2019}},
}